bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic effects of a single-dose nutritional ketone ester supplement on brain ketone and glucose metabolism in alcohol use disorder – a pilot study
Authors: Li Xinyi , Young Anthony J. , Pereira-Rufino Lais S. , Shi Zhenhao , Byanyima Juliana , Vesslee Sianneh , Reddy Rishika , Pond Timothy , Elliott Mark , Reddy Ravinder , Doot Robert K. , van der Veen Jan-Willem , Kranzler Henry R. , Reddy Nanga Ravi Prakash , Dubroff Jacob G. , Wiers Corinde E. 
Published: September 2023

AbstractIntroductionAcute alcohol intake decreases brain glucose metabolism and increases brain uptake of acetate, a metabolite of alcohol. Individuals with alcohol use disorder (AUD) show elevated brain acetate metabolism at the expense of glucose, a shift in energy utilization that persists beyond acute intoxication. We recently reported that nutritional ketosis and administration of ketone bodies as an alternative energy source to glucose reduce alcohol withdrawal severity and alcohol craving in AUD. However, the regional effects of nutritional ketosis on brain ketone (beta-hydroxybutyrate [BHB]) and glucose metabolism have not been studied in AUD.MethodsFive participants with AUD underwent two magnetic resonance imaging (MRI) sessions and 4 participants with AUD underwent two positron emission tomography (PET) sessions with18F-fluorodeoxyglucose. All participants completed one session without KE intervention and one session during which they consumed 395 mg/kg(R)-3-hydroxybutyl(R)-3-hydroxybutyrate Ketone Ester (KE) intervention (TdeltaS Global Inc.) before the scan. The order of the sessions was randomized. For the PET cohort, blood glucose and ketone levels were assessed and voxel-wise maps of the cerebral metabolic rate of glucose (CMRglc) were computed at each session. For the MRI cohort, brain anterior cingulate BHB levels were assessed using magnetic resonance spectroscopy.ResultsA single dose of KE elevated blood BHB and anterior cingulate BHB levels compared to baseline. Moreover, blood glucose levels were lower with KE than baseline, and whole-brain CMRglc decreased by 17%. The largest KE-induced CMRglc reductions were in the frontal, occipital, cortex, and anterior cingulate cortices.ConclusionThese findings provide preliminary evidence that KE administration elevates ketone and reduces brain glucose metabolism in humans, consistent with a shift from glucose to ketones as a brain energy source. Average reductions in CMRglc of 17% are similar to global average reductions documented with administration of 0.25-0.5 g/kg of alcohol. Documenting the clinical and neurometabolic effects of nutritional ketosis will yield fundamental knowledge as to its potential beneficial effects as a treatment for AUD and its underlying neural mechanisms.
The Application of Label-free Detection Using a Tapered Optical Fiber System for Head and Neck Cancer and Infectious Biomolecules
Authors: Collet Casey , Deng Cong , Ranathunga Chaminda , Banerjee Partha P. , Lin De-Chen , Sinha Uttam 
Published: September 2023

AbstractIntroductionHead and neck squamous cell carcinoma (HNSCC) is associated with high morbidity and mortality due to late detection. Tapered optical fiber sensors (TOFS) are biosensors with the potential application as a point-of-care device for detection of HNSCC biomarkers. TOFS uses optical fibers as transduction elements and antigen-antibody binding for the detection of target biomolecules. The present TOFS system was designed to achieve high specificity, sensitivity, and repeatability. To explore its application in HNSCC, we targeted the proinflammatory cytokine IL-8, known for its role in promoting tumorigenicity, metastasis, and angiogenesis in HNSCC. To validate our proof-of-concept experiment, a viral surrogate of SARS-CoV-2, Human Coronavirus OC43 (HCoV-OC43), was also tested.MethodsOur TOFS system contains four main parts: the tapered optical fiber, reservoir (cell), laser light source, and photodetector. The fiber is bitapered with a narrow waist region that anchors antibodies to detect target biomolecules. Light is transduced by the laser to the fiber where it travels through the down-taper region to the tapered waist followed by the up-tapered region and ultimately transmitted to the photodetector. The tapered waist facilitates the transformation of a single mode light to multiple modes, which reverts to a single mode of light as it continues through the up-taper region. Biomolecules introduced to the waist region alter the effective refractive index, which is reflected in the phase change of the wavelength. This is detected by the photodetector and quantified using Fouier analysis. Our tapered fibers were designed with antigen-antibody complexes targeting IL-8 and HCoV-OC43 to validate our TOFS design across two different antigens.ResultsTOFS with tethered mouse anti-human IgG (28nm) bound to dissolved IL-8 (14 nm) produces a measurable phase shift. As little as 10pg/ml or 7.1X105IL-8 molecules/μl was detected by the prototype device and the phase change represented in real-time the binding dynamic of IL-8 to the tethered IgG. To validate our proof-of-concept experiment, HCoV-OC43 dissolved in saliva was detected with a sensitivity of 50 viruses/mL.ConclusionsTOFS device is a highly sensitive system capable of detecting proteins, viruses, and other biomolecules. Selectivity of the system is guaranteed by specific antigen-antibody binding, supported by the detection of IL-8 and HCoV-OC43 at the femtomolar level. The long-term goal for TOFS is its application as a point-of-care device used for detection, monitoring, and surveillance of HNSCC as well as detection of other pathogens in the clinical setting.
Swine influenza A virus isolates containing the pandemic H1N1 origin matrix gene elicit greater disease in the murine model
Authors: Curran Shelly J. , Griffin Emily F. , Ferreri Lucas M. , Kyriakis Constantinos S. , Howerth Elizabeth W. , Perez Daniel R , Tompkins S. Mark 
Published: September 2023

ABSTRACTSince the 1990’s, endemic North American swine influenza A viruses (swFLUAV) contained an internal gene segment constellation referred to as the triple reassortment internal gene (TRIG) cassette. In 2009, the H1N1 pandemic (pdmH1N1) virus spilled back into swine, but did not become endemic. However, the pdmH1N1 did contribute the matrix gene segment (pdmM) to the swFLUAVs circulating in the pig population; which replaced the classical swine matrix gene (swM) found in the TRIG cassette, suggesting that the pdmM has a fitness benefit. Others have shown that swFLUAV containing the pdmM have greater neuraminidase activity and transmission efficiency compared to viruses containing the swM gene segment. We hypothesized that the matrix gene could also affect disease and utilized two infection models, resistant BALB/c and susceptible DBA/2 mice, to assess swFLUAV pathogenicity. We infected BALB/c and DBA/2 mice with a panel of H1 and H3 swFLUAVs containing the swM or pdmM gene and measured lung virus titers, morbidity, mortality, and lung histopathology. H1 influenza strains containing the pdmM gene caused greater morbidity and mortality in both resistant and susceptible murine strains, while H3 swFLUAVs caused no clinical disease. However, both H1 and H3 swFLUAVs containing the pdmM replicated to higher viral titers in the lungs and pdmM containing H1 viruses induced greater histological changes compared to swM H1 viruses. While the surface glycoproteins contribute to swFLUAV pathogenicity, and other genes also influence disease, these data suggest that the origin of the matrix gene also contributes to pathogenicity of swFLUAV viruses in mice.
CellPolaris: Decoding Cell Fate through Generalization Transfer Learning of Gene Regulatory Networks
Authors: Feng Guihai , Qin Xin , Zhang Jiahao , Huang Wuliang , Zhang Yiyang , Cui Wentao , Li Shirui , Chen Yao , Liu Wenhao , Tian Yao , Liu Yana , Dong Jingxi , Xu Ping , Man Zhenpeng , Liu Guole , Liang Zhongming , Jiang Xinlong , Yang Xiaodong , Wang Pengfei ,   The X-Compass Project Consortium, Yang Ge , Wang Hongmei , Wang Xuezhi , Tong Ming-Han , Zhou Yuanchun , Zhang Shihua , Chen Yiqiang , Wang Yong , Li Xin 
Published: September 2023

AbstractCell fate changes are determined by gene regulatory network (GRN), a sophisticated system regulating gene expression in precise spatial and temporal patterns. However, existing methods for reconstructing GRNs suffer from inherent limitations, leading to compromised accuracy and application generalizability. In this study, we introduce CellPolaris, a computational system that leverages transfer learning algorithms to generate high-quality, cell-type-specific GRNs. Diverging from conventional GRN inference models, which heavily rely on integrating epigenomic data with transcriptomic information or adopt causal strategies through gene co-expression networks, CellPolaris employs high-confidence GRN sources for model training, relying exclusively on transcriptomic data to generate previously unknown cell-type-specific GRNs. Applications of CellPolaris demonstrate remarkable efficacy in predicting master regulatory factors and simulating in-silico perturbations of transcription factors during cell fate transition, attaining state-of-the-art performance in accurately predicting candidate key factors and outcomes in cell reprogramming and spermatogenesis with validated datasets. It is worth noting that, with a transfer learning framework, CellPolaris can perform GRN based predictions in all cell types even across species. Together, CellPolaris represents a significant advancement in deciphering the mechanisms of cell fate regulation, thereby enhancing the precision and efficiency of cell fate manipulation at high resolution.
Neuronal aging is associated with declined autophagy caused by reduced functionality of cGAS-STING signaling
Authors: Passarella Sergio , Brandes Karina , Dankert Evelyn , Cavalli Paola , Kröger Andrea , Dieterich Daniela C. , Landgraf Peter 
Published: September 2023

ABSTRACTThe lifelong maintenance of cognitive abilities in an increasingly aging human society is one of the major challenges of future research and medical services. For this, a better understanding of the cellular aging processes in the mammalian brain is a fundamental requirement. In particular, the functioning of postmitotic neurons, which require special strategies for lifelong functionality, is still elusive in many details. Among many other hallmarks of neuronal aging, the impairment of autophagy as an essential element of cellular homeostasis is of particular importance. However, the mechanisms for regulating these processes have not yet been fully elucidated. Establishing anin vitromodel from primary cortical cells of the mouse brain, which shows the characteristic features of cellular senescence that are also observed in the total brain, we found the accumulation of dsDNA in the cytosol of neurons. Since dsDNA is a trigger for the activation of the cGAS-STING signaling and its primordial function is a non-canonical activation of autophagy, we analyzed its impact on aging neurons. We were able to demonstrate that the age-dependent downregulation of cGAS- STING signaling in neurons leads to an inhibition of autophagy at different levels. In contrast, activation of STING led to a complete rescue of autophagy in old neurons. Additionally, we found no evidence for age dependent cGAS-STING mediated IFN-I production. Hence, we propose that the primary function of cGAS-STING signaling in neurons is to maintain autophagy rather than contribute to age-related inflammation, and thus represents a target for therapeutic intervention.
SHIP1 modulation and proteome characterization of microglia
Authors: Ahat Erpan , Shi Zanyu , Chu Shaoyou , Bui Hai Hoang , Mason Emily R. , Soni Disha M. , Roth Kenneth D , Chalmers Michael James , Oblak Adrian L , Zhang Jie , Gutierrez Jesus A , Richardson Timothy 
Published: September 2023

AbstractMicroglia, the resident macrophage in brain, has gained significant attention due to their involvement in neurodegenerative diseases. Disease associated microglia (DAM) have been identified at sites of amyloid-beta plaques and neurodegeneration. Understanding microglial states in the aging brain has become crucial, especially with the discovery of numerous Alzheimer’s disease (AD) risk and protective variants in genes such asTREM2, CD33, APOE, ABCA7, PLCG2,andINPP5D, which are essential to microglia function1. Here we present a thorough examination of microglia-like cell lines and primary mouse microglia at the proteomic and transcriptomic levels to help illuminate the roles these genes and the proteins they encode play in various cell states. This analysis serves as a guide to the exploration of potential therapeutic targets in the context of neurodegeneration. INPP5D, which encodes the SHIP1 protein, is essential for microglia function. SHIP1 has emerged as a target of interest having been nominated as a therapeutic target by three teams within the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD)2. In this study, we compared the proteomic profiles of wildtype, SHIP1 heterozygous knockout, and homozygous knockout primary microglia. Our findings revealed significant proteomic alterations only in the homozygous knockout of the SHIP1 gene, revealing its impact on the microglial proteome. Additionally, we compared the proteomic and transcriptomic profiles of BV2 and HMC3 cells with primary mouse microglia because these cell lines are often used as microglial cellular models. Our results demonstrated a substantial similarity between the proteome of BV2 cells and mouse primary cells, while notable differences were observed between BV2 and human HMC3 cells, with some shared characteristics. Since SHIP1 functions as a lipid phosphatase that modulates phosphatidylinositol (PI) species, we conducted lipidomic analysis to quantify different phosphatidylinositols (PIs), phosphatidylinositol monophosphate (PIPs), and polyphosphoinositides (PPIs) in the HMC3 and BV2 cells. Under basal conditions, PI(3,4,5)P3 and PI(3,4)P2 species were detected at extremely low levels, making confident quantification challenging; however, PIP species within the overall pool were significantly changed upon SHIP1 overexpression in HMC3. This in-depth proteomic analysis of both mouse and human microglia, complemented by targeted lipidomic studies, enhances our understanding of these cellular models. The similarities between primary mouse microglia and the BV2 cell line is especially encouraging, supporting the use of this model for further investigations into the role that SHIP1 and other potential drug targets may play in the regulation of microglial states.
Undergraduates’ reactions to errors mediates the association between growth mindset and study strategies
Authors: Chouvalova Anastasia , Navlekar Anisha S. , Mills Devin J. , Adams Mikayla , Daye Sami , Anda Fatima De , Limeri Lisa B. 
Published: September 2023

ABSTRACTBackgroundStudents employ a variety of study strategies to learn and master content in their courses. Strategies vary widely in their effectiveness for promoting deep, long-term learning, yet most students use ineffective strategies frequently. Efforts to educate students about effective study strategies have revealed that knowledge about effective strategies is by itself insufficient for encouraging widespread and lasting changes. An important next step is to uncover factors that influence the decisions students make about study strategy use. We explored the association between beliefs about intelligence (mindset, universality, and brilliance) and study strategies. The most effective study strategies are error-prone, and beliefs about intelligence carry implications for whether errors are a normal and even beneficial part of the learning process (e.g., growth mindset) or signs of insufficient intelligence (e.g., fixed mindset). Therefore, we hypothesized that beliefs about and reactions to errors would mediate a relationship between beliefs about intelligence and study strategies. We tested this hypothesis by surveying 345 undergraduates enrolled in an introductory biology class at a public, research-active university in northwestern United States.ResultsConfirmatory factor analysis indicated that the internal structure of all measures functioned as expected in our sample. We fit a structural equation model to evaluate our hypothesized model. We found that mindset, but not universality nor brilliance, predicts variance in both beliefs about errors and reactions to errors. In turn, adaptive reactions to errors (but not beliefs about errors) are associated with the use of highly effective study strategies and spacing study sessions. There was a significant indirect relationship between growth mindset and spacing of study sessions.ConclusionsOur results provide evidence for a mechanism explaining the association between students’ mindset beliefs and academic outcomes: believing that intelligence is improvable is associated with more adaptive reactions to making errors, which correlates with choosing more error-prone and therefore more effective study strategies. Future interventions aimed at improving students’ study strategies may be more effective if they simultaneously target reacting adaptively to errors and emphasize that intelligence is improvable.
Differential mutation accumulation in plant meristematic layers
Authors: Amundson Kirk R , Marimuthu Mohan Prem Anand , Nguyen Oanh , Sarika Konsam , DeMarco Isabelle J , Phan Angelina , Henry Isabelle M , Comai Luca 
Published: September 2023

AbstractThe upper plant body is formed by the continued growth of shoot apical meristems. In angiosperms, meristems are organized in three cell layers that tend to remain clonally isolated. Somatic variants emerge when mutant cells overtake part or all of a meristem. During sexual reproduction, only one layer, the L2, contributes to the next generation by forming gametes. The L2 is known to frequently invade and replace the L3, while L1-L2 separation is persistent. The role of different meristem layers in mutation accumulation is unknown. We discovered a potato periclinal chimera in which the L2 and L3, but not the L1, are marked by a chromosomal translocation. This enabled the identification of plants regenerated from leaf protoplasts originating from either the L1 or L2+L3. Leveraging these layer-specific clones, we identified and compared mutations that accumulated in the layers in the clonal parent for several decades. Here we show that the L1 accumulates mutations at 1.9 times the rate of the L2, indicating that plants might protect the germline by mechanisms that reduce the rate of mutation accumulation in the L2. In contrast to these layer-specific mutations, we found no evidence of somatic mutation fixation in all three meristem layers. Our findings highlight how periclinal chimeras are formed by independent mutational processes in which a mutation-prone epidermal layer could increase clonal variation.
The anticancer chemotherapy drug 5-Fluorouracil has positive interaction with antibiotics and can select for antibiotic resistance inStaphylococcus aureus
Authors: Henderson Sara R. , Aras Leila H. , Evans Benjamin A. 
Published: September 2023

AbstractAntibiotic resistance is a major global issue in healthcare and understanding the drivers of resistance is key in developing effective strategies to counter it. Many non-antibiotic drugs, such as cancer chemotherapy drugs, can have antimicrobial properties but their effects on bacteria in the context of infection and drug resistance have only recently begun to be explored. Here we investigate the antimicrobial properties of the cancer drug 5-fluorouracil (5-FU) on the common human commensal and pathogenStaphylococcus aureus. 5-FU can be metabolized byS. aureusand ultimately results in the inhibition of ThyA, involved in the folate synthesis and thymine synthesis pathways. Bacterial growth was inhibited by 5-FU, and the drug had additive or synergistic interactions with the antibiotics trimethoprim and sulfamethoxazole. The addition of thymidine overcame the inhibitory effects of 5-FU. Strains ofS. aureusevolved in the presence of 5-FU developed mutations in the thymidine kinase genetdk, likely inhibiting the thymine salvage pathway. In mixtures of clinical trimethoprim-resistantS. aureusstrains and sensitive strains, the presence of 5-FU conferred a large fitness advantage to the resistant strains and selected for them over the sensitive strains. Together these data show that 5-FU has antimicrobial effects againstS. aureuswith these effects targeting the same pathway as existing antibiotics, and that the use of 5-FU in patients may be selecting for antibiotic-resistant bacteria.
1.7 GHz long-term evolution radiofrequency electromagnetic field with efficient thermal control has no effect on the proliferation of different human cell types
Authors: Goh Jaeseong , Suh Dongwha , Jeon Sangbong , Lee Youngseung , Kim Nam , Song Kiwon 
Published: September 2023

AbstractLong-term evolution (LTE) radiofrequency electromagnetic field (RF-EMF) is widely used in communication technologies. As a result, the influence of RF-EMF on biological systems is a major public concern, and its physiological effects remain controversial. In our previous study, we showed that continuous exposure of various human cell types to 1.7 GHz LTE RF-EMF at specific absorption rate (SAR) of 2 W/Kg for 72 h can induce cellular senescence. To understand the precise cellular effects of LTE RF-EMF, we elaborated the 1.7 GHz RF-EMF cell exposure system used in the previous study by replacing the RF signal generator and developing a software-based feedback system to improve the exposure power stability. This refinement of the 1.7 GHz LTE RF-EMF generator facilitated the automatic regulation of RF-EMF exposure, maintaining target power levels within a 3% range and a constant temperature even during the 72-h exposure period. With the improved experimental setup, we examined the effect of continuous exposure to 1.7 GHz LTE RF-EMF at up to SAR of 8 W/Kg of adipose tissue-derived stem cells and Huh7, HeLa, and B103 cells. Surprisingly, the proliferation of all cell types, which displayed different growth rates, did not change significantly compared with that of the unexposed controls. However, when the thermal control system was turned off and the subsequent temperature increase induced by the RF-EMF was not controlled during continuous exposure to SAR of 8 W/Kg LTE RF-EMF, cellular proliferation increased by 35.2% at the maximum. These observations strongly suggest that the cellular effects attributed to 1.7 GHz LTE RF-EMF exposure were primarily due to the induced thermal changes, rather than the RF-EMF exposure itself.