bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Cholesterol on the Biophysical Inhibition of Pulmonary Surfactant by Albumin
Authors: Veldhuizen Ruud , Milos Scott , Ruehlicke Jake , Yamashita Cory 
Published: November 2023

Pulmonary surfactant is a mixture of 85% phospholipids, 5–8% cholesterol and 5–8% surfactant proteins which forms a surface tension reducing lipid film at the air‐liquid interface of the alveoli. By reducing the surface tension to near 0mN/m values during compression (i.e. exhalation) surfactant maintains alveolar stability at low lung volumes and maintains proper lung compliance. The importance of surfactant is evident in Acute Respiratory Distress Syndrome (ARDS) in which the dysfunction of surfactant contributes to hypoxemia, regional areas of collapse and reduced lung compliance. Specifically, serum proteins, such as Albumin, leaking into the lung during ARDS have been shown to interfere with surfactant's ability to reach low surface tension. In addition, recent studies suggest that elevated cholesterol within surfactant also contribute to surfactant dysfunction in the setting of lung injury. Although the effects of cholesterol and serum proteins with surfactant have been studied independently, the interaction between the two has not previously been investigated. It was hypothesized that elevated levels of cholesterol within surfactant will make surfactant more susceptible to serum protein inhibition.MethodsBovine Lipid Extract Surfactant (BLES), a commercially available exogenous surfactant, was utilized and modified to generate samples with concentrations of 0, 2.5, 5 and 10% (w/w) cholesterol. Varying amounts of Bovine Serum Albumin (BSA) were subsequently added to each sample to attain concentrations of 0, 20, 30, 40 and 50 mg/ml. A constrained sessile drop surfactometer was used to determine the minimal achievable surface tensions during dynamic compression/expansion cycles.ResultsSamples with various levels of cholesterol, in the absence of BSA, reached minimum surface tension values of near 0mN/m during compression. At moderate levels of BSA (20 & 30mg/ml), minimum surface tensions were lower in surfactant samples containing cholesterol as compared to samples containing no cholesterol. Finally, at high BSA values, all surfactant samples had surface tension values that were higher than those at the lower BSA concentration but were not significantly different among the sample with different cholesterol concentrations.DiscussionContrary to the hypothesis, values of up to 10% cholesterol within surfactant do not appear to increase the susceptibility of surfactant to serum protein inhibition. In fact, the results suggest that cholesterol mitigates the effect of moderate levels of BSA on surfactant function. It is concluded that cholesterol within surfactant contributes to its resistance against inhibition by albumin.Support or Funding InformationCanadian Institutes for Health Research.
Increased Alveolar Size Persists in a Rodent Model of Bronchopulmonary Dysplasia
Authors: Centanni Ryan , Haraldsdottir Kristin , Braun Rudolf , Barton Greg , Goss Kara , Eldridge Marlowe , Pegelow David 
Published: November 2023

IntroductionBronchopulmonary dysplasia (BPD) is a chronic lung disease associated with premature birth. Hallmark pathologic features of BPD include increased alveolar wall thickness and reduced pulmonary vascular cross sectional area. Measurement of mean linear intercept (MLI) is a tool used to quantify alveolar size, where a higher MLI is suggestive of reduced alveolar surface area. Previous studies have shown an increased MLI in lungs from a BPD rat model in early postnatal life. However, it is unknown if these pathological changes last into adulthood. The purpose of this study was to quantify alveolar size using the mean linear intercept (MLI) technique in lung tissue sections from 7 and 14 day and 1 year old control and BPD rats.MethodsSprague Dawley rat pups were placed in hyperoxic (HYP, 85% O2) or normoxic (NORM, 21% O2) chambers within 12 hours of birth for a total of 14 days, then were moved to room air housing. At 7 and 14 days and 1 year of age, rats (n=2 rats per time point per exposure) were sacrificed and lung tissue sections were placed on slides and stained with hematoxylin and eosin (H&E). 9 images from each lung cross section were collected and analyzed. Alveolar air space was determined using the MLI method where horizontal grids were placed on images and intersections with the tissue were counted. For each image, MLI was calculated using the following equation: Lm = number of intersections/(grid length (um) × number of lines). The 9 values were averaged, giving an MLI score for each animal. Two‐way ANOVA was used to determine the main effect for age (7, 14, 360 d), condition (NORM vs HYP), and the interaction between age and condition. Statistical significance was defined as p < 0.05.ResultsHYP rats have a significantly greater MLI (p=0.01) compared to NORM rats at all time points. At 7 days, HYP rats had a 43% increase in MLI compared to NORM. At 14 days, HYP rats had an 18.5% increase. At one year, HYP rats had a 47% increase.ConclusionMean linear intercept is significantly increased a rat model of BPD, which persists well into adulthood. Enlargement of the distal airspaces likely plays a role in the diminished gas exchange observed in BPD.Support or Funding InformationNHLBI, R01 HL115061‐03, Suppl (Eldridge) & NHLBI, R01 HL115061 (Eldridge)
Mesenchymal and Epithelial Specific Deletion of Rac1 Prevents Lung Morphogenesis
Authors: Danopoulos Soula , Krainock Michael R. , Al Alam Denise 
Published: November 2023

BackgroundEpithelial‐mesenchymal interactions control specification, budding and branching in the developing lung. It is the spatio‐temporal expression of various signaling molecules in the different tissue compartments that drive the patterning of the lung. Our previous work demonstrated that the inhibition of Rac1 in mouse lung explants result in impaired branching morphogenesis and vasculogenesis. This role was primarily due to impaired mesenchymal cell proliferation and differentiation following Rac1 inhibtion. Therefore, we sought to determine the effect of epithelial and mesenchymal Rac1 deletion in vivo on lung development during the pseudoglandular and saccular stages.MethodsTo assess the effect of loss of epithelial or mesenchymal Rac1 on lung development in vivo, Rac1f/f animals were used to conditionally inactivate Rac1 using a Shh‐Cre or Dermo1‐Cre driver respectively. The lungs were then harvested from E13.5, E14.5 and E18.5 mutant (Cre+, Rac1f/f), heterozygous (Cre+,Rac1f/+), and control (Cre−,Rac1+/+) littermates. Upon collection, the lungs were either fixed and processed for embedding and histology, or were used for the extraction of RNA and gene expression analysis. Moreover, human lung explants were cultured in presence or absence of Rac1 inhibitor.ResultsEpithelial deletion of Rac1 resulted in lung hypoplasia starting at E13.5 and up to E18.5. During the early pseudoglandular stage the mutant lungs displayed dilated epithelial tips, and expressed high levels of Fgf10 and Wnt inhibitors. The mesenchymal deletion of Rac1 resulted in lungs that also appeared hypoplastic starting at E14.5 until E18.5. However, these mutant lungs displayed severe hypercellularity starting at E14.5. At E18.5, mesenchymal deletion of Rac1 resulted in severe reduction in saccular spaces. Transcription levels of Wnt inhibitors appeared decreased in the E14.5 mutants. Interestingly, both epithelial and mesenchymal Rac1 deletion resulted in embryonic lethality past E18.5. Using Wnt reporters, we showed that epithelial Rac1 deletion increased Wnt signaling, while mesenchymal Rac1 deletion decreased Wnt signaling. Moreover, we demonstrated that Rac1 is expressed in human fetal lung at different gestational stages. This expression is higher in the mesenchyme as compared to the epithelium. Treating human lung explants with Rac1 inhibitor resulted in impaired explant branching and growth.ConclusionIn summary, both epithelial and mesenchymal Rac1 are required for proper lung development, with opposing effects on Wnt signaling. Moreover, Rac1 seems to play an important role in human lung development. The precise mechanism by which epithelial vs mesenchymal Rac1 act, and the differential signaling molecules it regulates in each compartment require further investigation.Support or Funding InformationThis work is supported by the AHA.
Effects of Corn Oil, Compared to Extra Virgin Olive Oil, Intake on Lipoprotein and Subfraction Cholesterol Levels in Men and Women: Results from a Randomized, Controlled Feeding Study
Authors: Maki Kevin C , Lawless Andrea L , Kelley Kathleen M , Kaden Valerie N , Geiger Constance J , Palacios Orsolya M , Dicklin Mary R 
Published: November 2023

The aim of this analysis was to compare the effects of consuming foods prepared with corn oil (CO) versus extra virgin olive oil (EVOO) on fasting lipoprotein and subclass cholesterol levels in adults with elevated (130–199 mg/dL) low‐density lipoprotein cholesterol (LDL‐C) at baseline. A randomized, double blind, controlled‐feeding, crossover study design was used with an evaluable sample of 54 men and women with mean (SEM) baseline LDL‐C 147 (4.2) mg/dL. Subjects underwent two 21‐d controlled‐feeding periods, separated by a washout of ≥21 d. Feeding periods included 4 tbsp (~54 g) per day of CO or EVOO in 3 foods (muffin, dinner roll, yogurt). Fasting lipoprotein and subclass cholesterol levels were measured at baseline and at the end of each feeding condition. Density gradient ultracentrifugation (Vertical AutoProfile‐2 method, Atherotech Diagnostics Laboratory, Birmingham, AL) was used to assess total LDL‐C, small LDL3+4‐C, large LDL1+2‐C, intermediate‐density lipoprotein cholesterol (IDL‐C), total high‐density lipoprotein cholesterol (HDL‐C), large HDL2‐C, small HDL3‐C, total very low‐density lipoprotein cholesterol (VLDL‐C), large VLDL1+2‐C, and small VLDL3‐C. Total LDL‐C changed by a median of −8.6% during the CO condition versus −0.6% during EVOO feeding (P<0.0001). The larger reduction in total LDL‐C with CO was mainly attributable to changes (P<0.01 for CO vs. EVOO) in large LDL1+2‐C (−10.4%) and IDL‐C (−17.0%). CO feeding did not alter VLDL‐C, but EVOO raised the concentration by a mean of 10.7% (P<0.002 for CO vs. EVOO), due mainly to increased cholesterol in small VLDL3 particles (25.3%). Changes in both LDL‐C and VLDL‐C contributed to the more favorable median change in non‐HDL‐C with CO (−6.5%) compared with EVOO (0.8%; P<0.0001 for CO vs. EVOO). No significant differences between conditions in total HDL‐C, HDL2‐C or HDL3‐C responses were observed. In summary, foods made with CO produced more favorable effects than EVOO on atherogenic lipoprotein cholesterol (LDL, VLDL, non‐HDL) levels.Support or Funding InformationFunded by ACH Food Companies, Oak Brook, IL and PepsiCo., Purchase, NY
Interplay between Substrate Stiffness and TGF‐b1 on Cellular Traction Force and Migration of MDA‐MB‐231 Cells
Authors: LIN PO‐YEN , Chu Yeh‐Shiu , Lai Yi‐Ting , Lo Chun‐Min 
Published: November 2023

TGF‐β1 has been known to activate downstream signaling pathways of breast cancer cells and facilitate their invasive behaviors. In addition, our preliminary results show that MDA‐MB‐231 cells cultured on rigid substrates display higher traction forces and cell migration speed in comparison to cells cultured on more compliant substrates. The concept that a rise of contractile force due to increased ECM rigidity or TGF‐β1 induced scattering migration of MDA‐MB‐231 cells is intriguing, but the cross talk between ECM rigidity and TGF‐β1 remains to be elucidated. The goal of this study is to investigate the effect of substrate rigidity on TGF‐β1 induced changes of cell migration and traction forces of MDA‐MB‐231 cells. Collagen‐coated polyacrylamide substrates with a variety of Young's moduli (3.1, 7.4, and 10 kPa) were combined with fluorescence confocal imaging and digital image analysis to characterize a variety of cellular responses to substrate rigidity. Images of cell movement and the displacement of fluorescent beads embedded in polyacrylamide gels were taken every five minutes. Compared with control group without TGF‐β1 treatment, MDA‐MB‐231 cells on 7.4 kPa and 10 kPa gels demonstrated higher migration speed and smaller traction forces after TGF‐β1 treatment. However the addition of TGF‐β1 has little effect on traction forces or migration speed of MDA‐MB‐231 cells cultured on 3.1 kPa gels. Our results indicate that TGF‐β1 induced changes of scattering migration and traction forces are substrate rigidity dependent.Support or Funding InformationThis work was supported by the Ministry of Science and Technology, Taiwan.(Grant number: NSC 102‐2628‐B‐010‐010‐MY3)
Women's Empowerment and Food Security Status: A Global Comparative Study of Women Living in Rural and Urban Areas
Authors: Sinclair Kate , Ahmadigheidari Davod , Dallmann Diana , Melgar‐Quiñonez Hugo 
Published: November 2023

In recent decades, many efforts have been made to empower women, nonetheless, many gaps in gender equality still exist. These gender disparities have negative consequences not only for women but also for their families and society as a whole. Empowering women plays a vital role achieving and maintaining a food secure state. The objective of this study was to examine the association between indicators that are considered to contribute to women's empowerment and food security (FS).A sample of 15,334 rural women and 10,098 urban women was obtained from the 2015 Gallup World Poll, which is a nationally representative survey of individuals 15 years and older in 150 countries. The Food Insecurity Experience Scale within this dataset was used to categorize by FS status (i.e. Secure and Insecure) as the dependent variable, while women's empowerment indicators were used as independent variables. Crosstabs analyses and binary logistic regressions, for both rural and urban areas, were carried out using SPSS 23 Complex Sample.Several socio‐demographic characteristics, including education, marital status, employment status and income, were found to show significant differences between women living in rural and urban areas by FS status. Also, rural women were at a higher risk of being food insecure. Findings from the logistic regression show that rural women with higher levels of social support (OR 0.697), education (OR 0.175), control over life (OR 0.513), and personal health index (OR 0.402), had significantly higher odds of being food secure. Similar results were found among women living in urban areas in terms of education (OR 0.241), personal health index (OR 0.209) and control over life (OR 0.445). Finally, urban women who perceived being treated with respect (OR 0.438) also had higher odds of being food secure.The results confirm that the determinants of food security are highly complex, they do not act autonomously, and their effects are intertwined. Nonetheless, it is clear that factors contributing to women's empowerment play a key role in FS. Women's access to education is invaluable and should be prioritized worldwide as a means of improving FS. Shifting social norms to allow women to take control of life decisions is essential in achieving FS. Insuring one is able to maintain a good health status is pertinent to FS. As other studies have shown, strengthening social support is also a valuable tool to combat food insecurity, especially among rural women. Finally, living in urban areas provides increased and diverse opportunities for women compared to living rural areas. Addressing this opportunity gap in the future will be helpful in ensuring women's empowerment and FS for all.
The Critical Role of SENP1‐Mediated GATA2 DeSUMOylation in Graft Arteriosclerosis by Promoting Endothelial Activation
Authors: Qiu Cong , Wang Yuewen , Zhu Xiaolong , Song Lin , Zhang Haifeng , Qin Lingfeng , Tellides George , Min Wang , Yu Luyang 
Published: November 2023

Immune rejection mediated graft arteriosclerosis (GA) is the major cause of graft failure after allograft transplantation. The pathological process of GA starts from endothelial cell (EC) activation marked with inducible expression of endothelial adhesion molecules, which results in neointima formation, vasomotor dysfunction and consequent vascular occlusion. However, the comprehensive regulatory mechanism of EC activation during GA remains unclear. In the current study, dramatic but endothelium‐specific induction of SENP1, the major protease of small ubiquitin‐like modifier (SUMO) system, was observed in clinical graft rejection specimens by immunofluorescence staining, synchronized with endothelial activation mediated vascular remodeling. Of note, GATA2, the master transcriptional factor regulating expression of adhesion molecules, had similar expression pattern as SENP1. According to the correlation of endothelial SENP1 in GA, SENP1 endothelial conditional knockout mice (SENP1‐ecKO) were generated and subjected to an aorta transplantation model of GA. Endothelial SENP1 deficient graft maintained a better vessel function and had limited leukocyte recruitment and neointima formation during GA progression. Induction of endothelial adhesion molecules in early stages of GA was clearly diminished in the absence of endothelial SENP1 and this effect was confirmed in cultured mice aortic ECs as well as human EC bearing SENP1 deSUMOylase inactive mutant, indicating the regulatory effect of SUMOylation on EC activation. Indeed, constitutive SUMOylation of endothelial GATA2 was identified in SENP1‐ecKO graft and cultured EC, which was directly mediated by inflammation induced SENP1. Mechanistically, SUMOylated GATA2 demonstrated weakened stability and DNA binding onto promoters of adhesion molecule genes, resulting in dampened EC activation and consequently leukocyte‐endothelial adhesion and transmigration. More importantly, endothelial overexpression of GATA2 reversed the retarded GA progression in SENP1‐ecKO graft, further supporting the critical axis of SENP1‐GATA2 in endothelial inflammation. Taken together, we conclude that inflammation mediated SENP1 boosts GA by regulating GATA2 SUMOylation and consequent EC dysfunction.Support or Funding InformationThis work was supported by National Natural Science Foundation of China (Grant No. 81270357, 81422005 and 31470057), and Zhejiang Provincial Natural Science Foundation of China (Grant No. LR14H020002)
The role of mammalian polymerase theta in DNA repair
Authors: Sfeir Agnel 
Published: November 2023

Following telomere de‐protection chromosome ends are fused either by a Ligase 4‐dependent classical NHEJ process (C‐NHEJ) or using an alternative NHEJ pathway (alt‐NHEJ) mediated by Ligase 3 and PARP1. We recently investigated the differences in sequence fidelity between the two end‐joining reactions, and identified Polymerase theta (Polθ; encoded by Polq) as a critical alt‐NHEJ factor that introduces random nucleotides at fusion junctions. Polq inhibition suppresses alt‐NHEJ at telomeres that have lost shelterin protection, and blocks translocations at non‐telomeric loci. In parallel, loss of Polq results in increased rates of homology directed repair (HDR). Interestingly, depleting Polq in cells carrying mutations in the breast‐cancer susceptibility genes (Brca1 or Brca2) exacerbates chromosomal aberrancies and reduces cellular survival, suggesting that Polθ‐mediated alt‐NHEJ compensates when HDR is impaired.Polθ is an atypical A‐family DNA polymerase with an N‐terminal helicase‐like domain, a large central domain harboring a Rad51 interaction motif, and a C‐terminal polymerase domain capable of extending DNA strands from mismatched or even unmatched termini. In vitro experiments identified an evolutionarily conserved loop in the polymerase domain that is essential for synapsing DNA ends during end joining. To address the mechanism by which this low‐fidelity polymerase orchestrates double‐strand break repair we employed CRISPR/Cas9 gene editing and established cell lines with key Polθ mutations (PolqΔhelicase, PolqΔRAD51, PolqΔpolymerase, and PolqΔloop). Here we report on the impact of these mutations on Polθ function in promoting alt‐NHEJ and suppressing HDR, and address the importance of Polθ‐mediated alt‐NHEJ in survival of HDR defective cells.
Quality Control In 40S Ribosome Maturation
Authors: Karbstein Katrin 
Published: November 2023

While much is known about how ribosomes faithfully translate mRNAs into protein, how ribosomes are assembled within cells remains poorly understood. With ~ 2,000 ribosomes synthesized every minute ribosome assembly is the major metabolic activity of a growing cell. Given its profound energy requirements, ribosome assembly is tightly regulated in response to extracellular stimuli. In addition to providing sufficient numbers of ribosomes, cells must also ensure that the produced ribosomes are correctly assembled. This is important to safeguard their catalytic activity and extraordinary fidelity. We are exploring cellular mechanisms to ensure proper assembly of nascent 40S subunits.Support or Funding InformationR01 GM086451
MCAT2015: A New Focus On Biochemistry
Authors: Oyewole Saundra Herndon 
Published: November 2023

The 5th comprehensive review of the Medical College Admissions Test (MCAT), informed by the AAMC‐Howard Hughes Medical Institute's “Scientific Foundations for Future Physicians (SFFFP)” and the AAMC “Behavioral and Social Science Foundations for Future Physicians” reports, resulted in major revisions to the MCAT. Both reports focused on the competencies that entering medical students need to be successful in medical school and in medical practice. Among the changes in the MCAT is the addition of biochemistry as one of the science content areas. Biochemistry concepts were added based on data presented in the SFFFP report, survey data from medical school respondents, and input from stakeholders at various outreach events regarding the importance of biochemistry. The data suggest that knowledge of biochemistry fundamentals is increasingly important to the academic success of entering medical students.This presentation will provide an overview of the entire exam, with a focus on the importance of scientific inquiry and research skills as students apply their knowledge to answer questions based on passages describing research protocols. Students will be required to analyze data presented in various formats (tables, graphs, etc.) in order to answer passage‐based questions. This exam includes biochemistry content covered in many first semester biochemistry courses. The format of questions requires a deeper understanding of research methods and data analysis than the former MCAT. In addition, the new MCAT covers cellular and molecular biology content that is taught in introductory biology sequences. The speaker served on the MR5 Committee that made the recommendations for the new MCAT.