bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipids with negative spontaneous curvature decrease the solubility of the cancer drug paclitaxel in liposomes
Authors: Steffes Victoria , MacDonald Scott , Crowe John , Murali Meena , Ewert Kai K. , Li Youli , Safinya Cyrus R. 
Published: October 2023

AbstractPaclitaxel (PTX) is a hydrophobic small-molecule cancer drug that loads into the membrane (tail) region of lipid carriers such as liposomes and micelles. The development of improved lipid-based carriers of PTX is an important objective to generate chemotherapeutics with fewer side effects. The lipids 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and glyceryl monooleate (GMO) show propensity for fusion with other lipid membranes, which has led to their use in lipid vectors of nucleic acids. We hypothesized that DOPE and GMO could enhance PTX delivery to cells through a similar membrane fusion mechanism. As an important measure of drug carrier performance, we evaluated PTX solubility in cationic liposomes containing GMO or DOPE. Solubility was determined by time-dependent kinetic phase diagrams generated from direct observations of PTX crystal formation using differential-interference-contrast optical microscopy. Remarkably, PTX was much less soluble in these liposomes than in control cationic liposomes containing univalent cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), which are not fusogenic. In particular, PTX was not substantially soluble in GMO-based cationic liposomes. The fusogenicity of DOPE and GMO is related to the negative spontaneous curvature of membranes containing these lipids, which drives formation of nonlamellar self-assembled phases (inverted hexagonal or gyroid cubic). We used synchrotron small-angle x-ray scattering to determine whether PTX solubility is governed by lipid membrane structure (condensed with DNA in pellet form) or by local intermolecular interactions. The results suggest that local intermolecular interactions are of greater importance and that the negative spontaneous curvature-inducing lipids DOPE and GMO are not suitable components of lipid carriers for PTX delivery regardless of carrier structure.
ERK1/2 Inhibition Alleviates Noise-Induced Hearing Loss While Tempering Down the Immune Response
Authors: Lutze Richard D. , Ingersoll Matthew A. , Thotam Alena , Joseph Anjali , Fernandes Joshua , Teitz Tal 
Published: October 2023

AbstractNoise-induced hearing loss (NIHL) is a major cause of hearing impairment, yet no FDA-approved drugs exist to prevent it. Targeting the mitogen activated protein kinase (MAPK) cellular pathway has emerged as a promising approach to attenuate NIHL. Tizaterkib is an orally bioavailable, highly specific ERK1/2 inhibitor, currently in Phase-1 anticancer clinical trials. Here, we tested tizaterkib’s efficacy against permanent NIHL in mice at doses equivalent to what humans are currently prescribed in clinical trials. The drug given orally 24 hours after noise exposure, protected an average of 20-25 dB SPL in three frequencies, in female and male mice, had a therapeutic window >50, and did not confer additional protection to KSR1 genetic knockout mice, showing the drug works through the MAPK pathway. Tizaterkib shielded from noise-induced cochlear synaptopathy, and a 3-day, twice daily, treatment with the drug was the optimal determined regimen. Importantly, tizaterkib was shown to decrease the number of CD45 and CD68 positive immune cells in the cochlea following noise exposure, which could be part of the protective mechanism of MAPK inhibition.
The Effect of Synthetic Training Data on the Performance of a Deep Learning Based Markerless Biomechanics System
Authors: Templin Ty , Eliason Travis , Medjaouri Omar , Chambers David , Saylor Kase , Nicolella Daniel P. 
Published: October 2023

AbstractAs markerless motion capture technologies develop and mature, there is an increasing demand from the biomechanics community to provide kinematic data with the same level of accuracy as current gold standard methods. The purpose of this study was to evaluate how adding synthetic data to the training dataset of a deep learning based markerless biomechanics system impacts the accuracy of kinematic measurements during two functional movements. Synchronized video from multiple camera views was captured along with marker-based data from 9 subjects who performed 3 repetitions of countermovement jumps and squats. Including synthetic data to the training reduced lower limb error on average by 65.1% and 70.1% for the countermovement jump and squat movements, respectively. These results demonstrate the promising utility of supplementing the training of a deep learning markerless motion capture system with synthetic data.
Inhibition of dipeptidyl peptidase 4 allows accurate measurement of GLP-1 secretion in mice
Authors: Smits Mark M. , Galsgaard Katrine D. , Jepsen Sara Lind , Albrechtsen Nicolai Wewer , Hartmann Bolette , Holst Jens J. 
Published: October 2023

AbstractDipeptidyl peptidase (DPP)-4 and neprilysin (NEP) within few minutes degrade glucagon-like peptide 1 (GLP-1) in mice, generating small, inactive fragments of the peptide. Commercially available sandwich ELISA kits may not accurately detect intact GLP-1 (that is GLP-1[7–36]NH2) and these moieties, leading to underestimation of secretion and potentially misleading results. Single-site antibody approaches may pick up some fragments, yet require large plasma volumes and the accuracy is uncertain.We aimed to find a way to stabilize GLP-1 in mice allowing reliable measurement with sensitive commercially available ELISA kits. Non-anesthetized male C57Bl/6JRj mice were subjected to an oral glucose tolerance test (OGTT; 2 g/kg glucose via oral gavage). Blood was drawn from the retrobulbar plexus before and repeatedly during the OGTT and total and intact GLP-1 were measured by commercially available sandwich ELISA kits (Mercodia and Alpco, respectively). In blood samples taken 15 minutes after the glucose load, there were no increase in plasma GLP-1 concentration. There was a small insignificant increase in total GLP-1 (1-2 pmol/L) in samples taken at t=5 and t=10 minutes following the OGTT, but no rise in intact GLP-1. We then administered control (saline), or a DPP-4 inhibitor (valine pyrrolidide, 0.1 µmol/g or sitagliptin, 10 mg/kg) with or without a NEP-inhibitor (sacubitril, 0.3 mg/kg) 30 minutes before the OGTT. In the four inhibitor groups, intact GLP-1 increased during the OGTT (levels ranging between 4.04 [SD 2.87] and 15.53 [SD 6.76] pmol/L). The combination of sitagliptin with sacubitril gave the largest increase in intact GLP-1 levels. Finally, after injecting male C57Bl/6JRj mice with a known dose of GLP-1(7–36)NH2, the peak GLP-1 levels were significantly higher during sitagliptin, but not with the combination of sitagliptin/sacubitril. Both inhibitor groups, however, showed prolonged half-life of the GLP-1 plasma disappearance.We conclude that for measurements of GLP-1 secretion in mice with commercially available sandwich ELISA kits, it is necessary to consider both timing of blood sampling andin vivoinhibition of DPP-4. The described approach allows improved estimates of GLP-1 secretion for future studies. It is a limitation that DPP-4 and NEP inhibition may have metabolic effects by stabilizing the intact GLP-1 peptide (e.g. influencing levels of insulin and glucagon).
Sustainable production of 2,3,5,6-Tetramethylpyrazine at high titer in engineeredCorynebacterium glutamicumusing statistical design of experiments
Authors: Srinivasan Aparajitha , Chen-Xiao Kevin , Banerjee Deepanwita , Oka Asun , Pidatala Venkataramana R , Eudes Aymerick , Simmons Blake A. , Eng Thomas , Mukhopadhyay Aindrila 
Published: October 2023

AbstractBackgroundThe industrial amino acid production workhorse,Corynebacterium glutamicumnaturally produces low levels of 2,3,5,6-tetramethylpyrazine (TMP), a valuable flavor, fragrance and commodity chemical. We have previously reported serendipitous production of TMP inC. glutamicumstrains. In the present study, we demonstrate TMP production inC. glutamicumtype strain ATCC13032 via the expression of a heterologous TMP pathway in a defined medium followed by statistical design of experiments to understand the effect of the media composition on TMP production.ResultsTheC. glutamicumstrain engineered to overexpress acetolactate synthase and alpha-acetolactate decarboxylase fromLactococcus lactisproduced ∼0.8 g/L TMP in CGXII minimal medium supplemented with 40 g/L glucose in 24-deep well plates. This engineered strain also demonstrated growth and TMP production when the minimal medium was supplemented with up to 40% (v/v) hydrolysates derived from ionic liquid pretreated sorghum biomass. A screen for improvements in media composition on TMP titer was conducted using fractional factorial design that identified glucose and urea as significant components affecting TMP production. These two components were further optimized using response surface methodology. In the optimized CGXII medium, the engineered strain could produce up to 3.56 g/L TMP (4-fold enhancement in titers and 2-fold enhancement in yield, mol/mol) from 80 g/L glucose and 11.9 g/L urea in shake flask batch cultivation.ConclusionsWe engineered the industrially relevant host,C. glutamicumfor targeted production of TMP by heterologous expression of pathway proteins. We demonstrated the capability of the engineered strain for growth and TMP production utilizing real world carbon streams such as hydrolysates. We further identified glucose and urea as the key minimal media components significantly affecting TMP production using statistical media optimization.
40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by GABAergic Neuronal Inhibition
Authors: Toso Alessandro , Wermuth Annika P. , Arazi Ayelet , Braun Anke , Jong Tineke Grent-‘t , Uhlhaas Peter J. , Donner Tobias H. 
Published: October 2023

AbstractThe 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, non-invasive physiological biomarker for schizophrenia and related neuropsychiatric disorders. The 40 Hz ASSR might be amplified by synaptic interactions in cortical circuits, which are, in turn, disturbed in neuropsychiatric disorders. Here, we tested whether the 40 Hz ASSR in human auditory cortex depends on two key synaptic components of neuronal interactions within cortical circuits: excitation via N-methyl-aspartate glutamate (NMDA) receptors and inhibition via gamma-amino-butyric acid (GABA) receptors. We combined magnetoencephalography (MEG) recordings with placebo-controlled, low-dose pharmacological interventions in the same healthy human participants. All participants exhibited a robust 40 Hz ASSR in auditory cortices, especially in the right hemisphere, under placebo. The GABAA receptor-agonist lorazepam increased the amplitude of the 40 Hz ASSR, while no effect was detectable under the NMDA-blocker memantine. Our findings indicate that the 40 Hz ASSR in auditory cortex involves synaptic (and likely intracortical) inhibition via the GABA-A receptor, thus highlighting its utility as a mechanistic signature of cortical circuit dysfunctions involving GABAergic inhibition.Significance statementThe 40 Hz auditory steady-state response is a candidate non-invasive biomarker for schizophrenia and related neuropsychiatric disorders. Yet, the understanding of the synaptic basis of this neurophysiological signature in humans has remained incomplete. We combined magnetoencephalography (MEG) recordings with placebo-controlled pharmacological interventions in healthy human subjects to test the modulation of the 40 Hz ASSR in auditory cortex by two synaptic components that have been implicated in the generation of neuronal oscillations in cortical microcircuits: glutamate N-methyl-aspartate glutamate (NMDA) receptors and gamma-amino-butyric acid (GABA) -A receptors. Boosting GABAergic transmission, but not blocking NMDA-receptors, increased the amplitude of this ASSR. Thus, GABAergic inhibition modulates 40 Hz steady-state responses in auditory cortex.
Three-dimensional localization of fluorescent proteins in livingEscherichia coli
Authors: Karempudi Praneeth , Gras Konrad , Amselem Elias , Zikrin Spartak , Elf Johan 
Published: October 2023

Abstract3D localization of fluorescent proteins (FPs) in living bacteria has been challenging due to the low signal-to-background ratio of the FPs and the relatively uncertain positioning of the cells in the optical reference system. Using mother-machine microfluidic devices together with deep learning, we present an approach that enables accurate 3D localization of FPs inEscherichia coliover long periods. We describe a method to simulate ground truth training data for the deep learning network based on background models generated from experimental data. We test the method by studying how chromosomal loci are relocated in 3D over theE. colicell cycle. Since the cells are radially symmetric, we expect the same width and height distribution of fluorophores if the 3D positions are correctly determined. We observe this pattern experimentally for all the labelled loci on the chromosome. Interestingly, some loci are located exclusively in the periphery of the nucleoid, while others are more confined to the core of the nucleoid. This method enables studying any chromosomal loci inside livingE. colicells in high-throughput.
Engineering the soil bacteriumPseudomonas synxantha2-79 into a ratiometric bioreporter for phosphorus limitation
Authors: Larsson Elin M. , Murray Richard M. , Newman Dianne K. 
Published: October 2023

AbstractMicrobial bioreporters hold promise for addressing challenges in medical and environmental applications. However, the difficulty of ensuring their stable persistence and function within the target environment remains a challenge. One strategy is to integrate information about the host strain and target environment into the design-build-test cycle of the bioreporter itself. Here, we present a case study for such an environmentally-motivated design process by engineering the wheat commensal bacteriumPseudomonas synxantha2-79 into a ratiometric bioreporter for phosphorus limitation. Comparative analysis showed that an exogenous P-responsive promoter outperformed its native counterparts. This reporter can selectively sense and report phosphorus limitation at plant-relevant concentrations of 25-100µM without cross-activation from carbon or nitrogen limitation or high cell densities. Its performance is robust over a field-relevant pH range (5.8-8), and it responds only to inorganic phosphorus, even in the presence of common soil organic P. Finally, we used fluorescein-calibrated flow cytometry to assess whether the reporter’s performance in shaken liquid culture predict its performance in soil, finding that although the reporter is still functional at the bulk level, its variability in performance increases when grown in a soil slurry as compared to planktonic culture, with a fraction of the population not expressing the reporter proteins. Together, our environmentally-aware design process provides an example of how laboratory bioengineering efforts can generate microbes with greater promise to function reliably in their applied contexts.
Assessing the psychometric properties of a questionnaire evaluating the residents’ perception of peer assisted learning in emergency medicine residency program
Authors: Kabli Ammar , Eltouny Sarah , Gouda Enas 
Published: October 2023

PurposeThis study aims to measure the perception of the residents regarding peer assisted learning in emergency medicine residency program as well as assessing the psychometric properties of the questionnaire used as the research tool.Design/methodology/approachA descriptive cross-sectional study was conducted at King Abdullah Medical City, Saudi Arabia, Makkah on a Convenience sample of Emergency Medicine residents who completed peer assisted learning sessions. Data were collected through a questionnaire evaluating the residents’ perception of Peer Assisted Learning. Descriptive statistics were used and statistical significance was set at p < 0.05. The Peer Assisted Learning (PAL) satisfaction questionnaire was tested for construct validity and reliability. Exploratory Factor Analysis (EFA) was conducted. The reliability of the used questionnaire was assessed using Cronbach’s coefficient alpha.FindingsThe study showed that the PAL questionnaire yielded four factors. The four factors are labeled as the following: Factor 1: Cognitive congruence, Factor 2: Social congruence; Factor 3: Teaching skills in Peer Assisted Learning (PAL) session; and Factor 4: Professional development. These results indicated that questionnaire has a good structure validity. In addition, the study showed high internal consistency of the questionnaire. Cronbach’s alpha coefficient value for the total scale was 0.88. The perception of residents was assessed and results revealed residents’ satisfaction regarding Peer Assisted Learning.Originality/valueUp to the authors’ knowledge, this is the first study which assessed the psychometric properties of a questionnaire measuring the residents’ perceptions regarding Peer Assisted Learning. The study contributed to improving information regarding the psychometric properties and usefulness of PAL questionnaire.
The environmental performance of agricultural production trusteeship from the perspective of planting carbon emissions
Authors: Zhao Lijuan , Liu Yan , Shi Junhong 
Published: October 2023

PurposeIn the context of carbon peaking and neutrality, effectively controlling agricultural carbon emissions has gained academic attention. As an essential form of agricultural service scale management, this study investigates whether and how trusteeship affects the carbon emission behavior in planting production.Design/methodology/approachThe authors established a theoretical framework to analyze the impact of agricultural production trusteeship on carbon emissions from planting. China's provincial panel data in the 2012–2021 period were selected to test the impact, mechanisms and heterogeneity of agricultural production trusteeship on carbon emissions from planting using the bidirectional fixed effect model and the panel correction standard error regression model.FindingsThe findings indicate that agricultural production trusteeship significantly inhibits carbon emissions from planting, especially in the dimensions of fertilizer input, pesticide application, agricultural film use and mechanical fuel. Agricultural production trusteeship primarily affects the intensity of these carbon emissions through contiguous farmland management and planting structure adjustment. Further examinations revealed that the influence of agricultural production trusteeship on carbon emissions from planting was heterogeneous with respect to geographical location, proportion of non-farming income and scale of agricultural production.Originality/valueThis study is the first to systematically evaluate the impact of agricultural production trusteeship on carbon emissions from planting.
Exploring the relationship between social media use and anti-luxury behavior: implications for interactive marketing strategies
Authors: Le Hoang Tran Phuoc Mai , Park Jungkun , Nguyen Trang Thi , Yun Jeewoo 
Published: October 2023

PurposeThe study explores different types of anti-luxurians on social media (SM), the characteristics of luxury brands, tendencies to disengage and the opposition to them to propose future directions for luxury marketing in the post-pandemic world.Design/methodology/approachA qualitative approach was employed, wherein 979 posts from SM platforms were analyzed with the text analytics software package KH Coder through word-frequency analysis and an inductive technique.FindingsThe analysis identified the presence of eight types of online anti-luxurians: true luxurians, nature-experienced lovers, life simplifiers, anti-haulers, highly expected consumers, natural environment protectors, antidiscrimination consumers and historic-politic antagonists. Their degree of disengagement and opposition were discussed and graphically mapped.Originality/valueThis is the first study to discover various types of anti-luxurians on SM platforms and graphically map their level of disengagement and opposition toward luxury brands. This study fills an existing critical gap in the luxury marketing literature.
Sustainability enablers with price-based preservation technology and carbon reduction investment in an inventory system to regulate emissions
Authors: Yadav Shikha , Borkar Aman , Khanna Aditi 
Published: October 2023

PurposeWith the pressing need for environmental conservation, regulatory authorities are actively looking for measures to prevent global warming. In the proposed inventory model for deteriorating items, demand is dependent on the selling price and green technology investment (or carbon reduction investment) for the green product (GP), as well as an investment in price-based preservation technology to slow down the pace of deterioration. Furthermore, emission reduction measures are put in place to reduce carbon emissions (CEs).Design/methodology/approachThe current study executed a thorough literature review to determine how to improve supply chain management performance. Furthermore, assumptions are made to fill research gaps, and a mathematical model is created to address the problem mentioned above. To collect the data, the available inventory literature was reviewed. Additionally, numerical illustrations and sensitivity analyses are presented to emphasize the model's robustness.FindingsThe research indicates that it is more prudent to invest in preservation technology based on its selling price in order to control the rate of deterioration. In addition, the proposed model facilitates the management of deteriorated waste through salvage trading and emission reduction investment. The findings validate sustainable practices with a 20.86% increase in profit and a 21.4% decrease in CEs, thereby signifying environmental and economic benefits.Originality/valueThe proposed model enhances understanding of the impact of investments in price-based preservation technology and carbon reduction efforts on consumer perceptions of their intention to purchase GPs. Moreover, the study provides valuable insights by identifying important recommendations for policymakers regarding areas that require further investigation. This guideline can help identify both current and unexplored gaps, enabling researchers to direct future research efforts toward producing new products.