bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fracture Property Experimentation On Hadrosaurid Dinosaur Wavy Enamel Reveals Energy‐Robbing Crack Deflection and Channeling To Localize Damage: A Rare Case of Mammalian‐Like Dental Sophistication In Reptiles
Authors: Erickson Gregory M , Kuhn‐Hendricks Stephen M , Krick Brandon A 
Published: November 2023

Reptiles rarely approached the biomechanical sophistication of feeding or dietary diversity seen in mammals. Their teeth are typically non‐occluding, semi‐conical structures with simplistic parallel‐crystalite enamel surrounding an orthodentine core. Conversely, most mammals possess multi‐cusped teeth that are drawn across one another during mastication and self‐wear to their functional morphology. Mammalian enamel is complex ‐‐ a fiberglass‐like composite composed of bundles of hydroxyapatite crystals known as prims, surrounded by compliant proteinacous sheaths. Among the most sophisticated prism architectures is the modified radial enamel (MRE) of grazing ungulates whose coarse tooth surfaces enable grinding of tough, abrasive‐laden plant matter. MRE conveys exceptional fracture toughness and controlled fracture propagation minimizing damage to the brittle enamel crests. Hadrosaurid (duck‐billed dinosaurs) are notable in independently evolving self‐wearing grinding dentitions and complex wavy enamel (WE) composed of folded layers of hydroxyapatite crystals whose biomechanical import is unknown. We tested the hypothesis that WE served an analogous role to ungulate MRE by: 1) tribologically modeling the effects on hadrosaurid occlusal surfaces should a section of enamel become fractured; 2) introducing enamel fractures to the teeth of hadrosaurids, outgroups lacking WE, and horses and bison using Vickers‐tipped indenters; 3) testing for controlled‐crack propagation using Watson's Two‐Sample Test of Homogeneity; and 4) contrasting the results in comparative ecological contexts. Removal of enamel sections leads to aberrant self‐wear to hadrosaurid chewing pavements (= “wave mouth” in equine veterinary science) inhibiting functionality. Non‐WE enamels show isotropic fracturing and catastrophic damage to the enamel shells. WE and MRE three‐dimensionally limit damage in enamel crests through energy‐robbing crack deflection at kinks in the enamel fabrics or prism boundaries and channeling perpendicular to the enamel‐dentine junction. Hadrosaurid WE represents an alternative reptilian solution for damage resistance in grazing taxa, one that evolved millions of years earlier than in mammalian ungulates. Our findings add to a growing body of evidence that material properties are preserved in fossil teeth and can be used to explore dental form and function throughout the fossil record and to develop biologically‐inspired industrial materials.Support or Funding InformationNSF EAR 0959029 awarded to GME
The nuclear lamins are major determinants of nuclear architecture
Authors: Goldman Robert , Adam Stephen A. , Goldman Anne E. , Shimi Takeshi , Kittisopikul Mark , Jaqaman Khuloud , Turgay Yagmur , Medalia Ohad 
Published: November 2023

The major structural components of the nuclear lamina are the Type V intermediate filament proteins, the nuclear lamins. There are four nuclear lamin isoforms (Lamins A, C, B1 and B2), which interact along with their binding partners to form a molecular interface between the inner nuclear envelope membrane and chromatin, the nuclear lamina in mammalian cell nuclei. Evidence has accumulated that the lamins play important roles in DNA replication, transcription, chromatin organization, DNA damage repair, the regulation of nuclear size and shape, and the disassembly and reassembly of the nucleus during mitosis. In addition, hundreds of mutations have been discovered in the gene encoding lamins A and C that cause a wide range of human diseases known as the “laminopathies”. Our studies of the nuclear phenotypes resulting from these mutations have provided important insights into the structure and function of both the A‐ and B‐type lamins in normal cells; especially those mutations which cause typical and atypical forms of premature aging (progeria). To date our observations of progeria nuclei demonstrate that the lamins play regulatory roles in the positioning and epigenetic modifications of chromatin and in premature replicative senescence. These studies have also revealed that the A‐ and B‐type lamins form different networks within the lamina. Expanding on this finding we have carried out 3D‐Structured Illumination Microscopy (3D‐SIM) analyses to show that the 4 lamin isoforms assemble into different filamentous meshworks within the lamina of normal human diploid and mouse embryonic fibroblasts. These findings are now being correlated with higher resolution images obtained by cryo‐EM tomographic analyses. 3D‐SIM is also revealing a close association between lamin filaments in the NL and peripheral domains of heterochromatin. These associations appear to be altered in the nuclei of cells in which one or more lamins are depleted.Support or Funding InformationThis work is supported by National Institutes of Health grants GM106023 and the Progeria Research Foundation.
Single molecule transcription factor dynamics in mammalian cells and the syncytial Drosophila embryo
Authors: Darzacq Xavier , Mir Mustafa 
Published: November 2023

Formation of the large protein complexes regulating transcription such as the pre‐initiation complex (PIC) is the result of equilibrium in between the frequency at which its principal components assemble and disassemble. To date a lot of information has been collected on how the off rate of a specific interaction is regulated. Here I will concentrate on two mechanisms controlling the on rate of proteins assembly at the level of their ability to sample the nucleoplasm using efficient strategies to search for their targets.During early development in the Drosophila embryo, cell fates are determined over the course of just 2 hours with exquisite spatio‐temporal precision. One of the key regulators of this process is the morphogen Bicoid that is enriched at the anterior of the embryo establishing polarity in a concentration dependent manner. Bicoid has also been suspected to play a role in the posterior where there are only a few molecules per nucleus but the lack of a mechanism for such an activation lead to much controversy. Here we use lattice light sheet microscopy to overcome the technical barriers of sample thickness and auto‐fluorescence to characterize the single molecule dynamics of Bicoid. We find that Bicoid binds to DNA transiently consistent with its concentration modulated activity. When analyzing the few molecules present in the posterior nuclei we observed a significant dynamic change affecting the on rates of binding as well as massive clustering of bicoid molecules. In the context of a concentration dependent model for bicoid activity, this data is consistent with a locus dependent and regulated transcriptional function in the drosophila embryo posterior. Different mechanisms of regulation as well as current experiments to sort them apart will be discussed.Support or Funding InformationFunding was provided by the National Institute of Health grants (U54‐DK107980) and (U01‐EB021236) to XD. California Institute for Regenerative Medicine (CIRM, LA1‐08013 to XD)
Using kinase regression to elucidate host signaling pathways that control infection
Authors: Kaushansky Alexis , Arang Nadia , Kain Heather S. , Glennon Elizabeth K. , Dudgeon Denali R. , Walter Emily N.F. , Gujral Taranjit S. 
Published: November 2023

Intracellular pathogens have extensive needs from their host cells. For example, Plasmodium parasites are dependent on hepatocyte infection for life cycle progression. During their residence within the hepatocyte, malaria parasites rely on their host for protection against cell death and for the acquisition of nutrients that supports their development. Unfortunately, technical hurdles have led to only a sparse knowledge of molecular factors that regulate liver stage malaria infection. Here, we assessed 37 host‐targeted kinase inhibitors for their capacity to eliminate malaria‐infected hepatocytes. We used these data, along with pre‐existing activity profiles of each inhibitor against 300 host kinases, to inform a predictive computational model that identified host kinases which facilitate Plasmodium liver stage infection. Our predictions yielded 49 kinases, including five kinases previously described to impact infection and 44 novel regulators of infection that include multiple Receptor Tyrosine Kinases and members of the Protein Kinase C cascade. Our approach also facilitated the prediction of several novel host‐targeted kinase inhibitors of infection, including multiple compounds which have already been used in humans and are active against Plasmodium parasites in vitro and in vivo. Moreover, this straight‐forward approach facilitates a kinome‐wide assessment of critical host factors involved in infection by a wide range of pathogens. By comparing host regulators of infections by parasites, bacteria and viruses, we hypothesize multiple kinases that regulate cellular processes that underlie infection by a wide variety of pathogens. This suggests that host‐targeted kinase inhibitors could curtail a wide variety of infections.Support or Funding InformationR00AI111785
Tart Cherry Juice Improves Visual Sustained Attention and Subjective Memory Ability in Older Adults
Authors: Chai Sheau C , Davis Kristina , Wright Regina S , Zhang Zugui , Luo Jing , Lee Krystal 
Published: November 2023

Tart cherries or their bioactive components have been shown to improve neuronal‐behavioral performance and decrease levels of oxidative and inflammatory markers. However, the ability of tart cherries to improve cognitive function in older adults has not been investigated. Hence, a randomized placebo‐controlled trial was conducted to evaluate whether older adults consuming 16 fluid ounces (fl. oz) of tart cherry juice daily for 12 weeks would improve cognitive function. Thirty‐seven (N=37) older adults between the ages of 65–80 years were recruited. Participants were randomly assigned to consume tart cherry juice or placebo daily for 12 weeks. Subjective memory and objective cognitive performance was assessed using a validated questionnaire and a standardized battery of tests. Fasting blood samples were also collected to measure oxidative stress and inflammatory biomarkers. Statistical analysis was performed using a nonparametric one‐way ANOVA with Wilcoxon in SAS Version 9.2. Our findings indicate that perception of everyday memory ability (P=0.0268) and visual sustained attention (P<0.0001) increased significantly in the tart cherry group, as compared to the placebo group, from baseline to posttest. 8‐oxoguanine glycosylase, a DNA glycosylate enzyme that are necessary for the excision 8‐oxoguanine and repair of a damaged DNA was significantly increased in the tart cherry group compared with the placebo group. Inflammatory markers were not altered by tart cherry juice or placebo. The findings of the present study suggest that tart cherry juice may improve cognitive function through its anti‐oxidative properties.Support or Funding InformationCherry Marketing Institute
Femoral and L5 Spine Trabecular Bone Are Differentially Influenced by Dietary Calcium Restriction and Genetics in Growing Mice
Authors: Chanpaisaeng Krittikan , Reyes‐Fernandez Perla C. , Mace Sarah , Replegle Rebecca A. , Lan Xu , Fleet James C. 
Published: November 2023

Trabecular bone (Tb) has a high surface‐to‐mass ratio that makes it valuable for rapid exchange of calcium (Ca) ions in times of physiologic need (i.e. when dietary Ca intake is low). Previous studies showed there is heterogeneity in Tb structure at different skeletal sites and this might explain why certain sites are more vulnerable to osteoporosis. We hypothesized that peak Tb mass at the distal femur and lumbar spine is differentially regulated by dietary Ca intake, genetics, or their interaction. Sixty‐two (62) genetically distinct mouse lines were fed diets with basal (0.5%) or low (0.25%) Ca levels from 4 to 12 wks of age (n=8/diet/line). At termination, the right femur and L5 vertebrae were removed and Tb was analyzed by micro‐computed tomography (μCT). Means were adjusted for the confounding influence of body size by ANCOVA. The response of μCT parameters to dietary Ca restriction (RCR) was calculated and used as a separate parameter. On the basal diet, the L5 spine is more dense than femur, i.e. Tb mass (bone volume/total volume, BV/TV), number (Tb.N), and thickness (Tb.Th) were significantly higher, while separation (Tb.Sp) was lower. The Structural model index (SMI) indicates that Tb structure was more rod‐like in femur (i.e. a weaker structure) and more plate‐like in spine (i.e. a stronger structure). Low dietary Ca intake reduced BV/TV and made Tb structure more rod‐like at both sites. However, dietary Ca restriction had a differential effects on Tb bone at each site, e.g. there was more loss of Tb.N in the femur (RCR = −7.58% (femur) vs. −2.15% (spine)) suggesting there is a greater impact of low Ca intake on the structural integrity of femoral Tb compared to L5 spine Tb. There was a large phenotypic diversity across the 62 lines for all femur and spine parameters, suggesting that genetics is a major regulator of Tb. Consistent with this, the narrow sense heritability (h2) was high for all parameters at both sites (e.g. BV/TV in the basal diet group; h2 = 0.52 in femur and 0.56 in spine). Similarly, the RCR was significantly different among lines for all parameters, reflecting gene‐by‐diet (GxD) interactions, but the effect was more modest, e.g. BV/TV RCR, h2 = 0.37 for femur and 0.25 for spine. Lastly, there was a significant site‐by‐line interaction affecting the basal and RCR parameters that indicates site‐specific genetic effects on Tb. Our research is important because it demonstrates that a complex interaction exists between dietary Ca intake and genetics and this can influence development of peak Tb mass in the femur and L5 spine. Further genetic mapping studies will be conducted to identify the loci and candidate genes that account for these genetic and GxD effects.Support or Funding InformationSupported by NIH award ES019103 to JCF and Royal Thai Government Scholarship to KC
Hemoglobinopathies and Child Feeding Practices as Predictors of Anemia in Rural Laotian Children: Evidence from the Lao Zinc Study
Authors: Barffour Maxwell Adusei , Hinnouho Guy‐Marino , Wessells Kimberly Ryan , Brown Keneth H , Chanhthavong Bigphone , Ratsavong Kethmany , Sanchaisuriya Kanokwan , Kounnavong Sengchanh , Fucharoen Supan , Hess Sonja Y 
Published: November 2023

Understanding the genetic and nutritional determinants of anemia is critical in designing interventions. We compared differences in anemia by hemoglobinopathy status and child feeding practices, using baseline data of 6–23 month old children (n=900) from rural Khammouane district, Lao PDR, who are participating in the Lao Zinc Study. First, we explored the associations between anemia and two structural hemoglobin variants, namely a) Hemoglobin (Hb) E‐trait (defined as normal (HbAA), homozygote‐HbEE or heterozygote (HbEA)), and b) Hemoglobin F (defined as hereditary persistence of fetal hemoglobin (HPFH) if relative abundance ≥5%, or normal if otherwise). Next, on the basis of the results of the anemia‐hemoglobinopathy analyses, we evaluated the associations between anemia and child feeding practices, stratified by HbE‐trait. We defined breastfeeding (BF) as at least one‐time breastfeeding in the past month. Using World Health Organization (WHO) guidelines, adequate meal frequency (AMF) was defined as a minimum meal frequency of 2 (6–8 month) or 3 (9–23 month) if BF or 4 if non‐BF. Adequate dietary diversity (ADD) was defined as consumption of at least 4 of 7 food groups as specified by the WHO, in the past 24 hours. Consumption of animal source food (ASF) was defined as intake of at least 1 of 4 animal source foods in the past 24 hours. Anemia was defined as Hb <110 g/l. The distribution of children by HbE was 31% (HbAA), 57% (HbEA) and 12% (HbEE). Prevalence of HPFH was 15%. The prevalence of breastfeeding was 67%, AMF was 12%, consumption of ASF was 72% and ADD was 24%. Overall anemia prevalence was 51%, although prevalence differed by HbE status (40% for HbAA, 53% for HbEA and 70% for HbEE; p<0.001) and by HbF status (67% for HPFH and 48% if otherwise; p<0.001). In a multivariate logistic regression model including HbE, HbF and age, the odds of anemia was increased in children with HbEA (OR=1.7, P=0.001) and HbEE (OR=3.4; P<0.001) relative to the HbAA children. HbF was not associated with increased anemia risk after adjusting for HbE and age. In the HbE‐stratified analyses, we found no evidence of an association between anemia and either AMF or ASF, irrespective of HbE or BF status. However, in HbAA children, ADD was associated with a lower anemia prevalence in BF children (OR=0.44, P=0.037), but not non‐BF children (OR=1.64, P=0.303). Our data suggests that in this population, hemoglobinopathies, breastfeeding and complementary feeding practices are important predictors of anemia.Support or Funding InformationFunding for this research was provided by the Mathile Institute for the Advancement of Human Nutrition, the Micronutrient Initiative and the Bill & Melinda Gates Foundation.
Chestnut Leaf Extract Increases Sensitivity of Breast Cancer Stem Cells to Paclitaxel by Inhibiting Nrf2 Activity
Authors: WOO YAEJIN , Oh Jisun , Kim Jong‐Sang 
Published: November 2023

Tumor cells consist of various clonal subpopulations, thus displaying heterogeneous tumorigenicity. Only a subset of tumor cells, called cancer stem cells (CSCs), uniquely possesses high potency to initiate tumorigenesis and to locally or systematically disseminate tumor cells. Based on their properties, CSCs come to be a critical target for the development of chemotherapeutic strategies. Interestingly, it has been known that Nrf2‐mediated antioxidant enzymes are highly expressed in CSCs, which may be responsible for lowering the intracellular ROS level and the vulnerability to chemotherapeutic agents. As anticancer drugs usually utilize ROS as an arsenal for killing cancer cells, we hypothesized that suppression of Nrf2 activity may increase susceptibility of CSCs to anticancer drugs, improving their therapeutic efficacy. Our findings demonstrate that MCF‐7 CSCs having a CD44high/CD24low phenotype formed mammospheres and highly expressed Nrf2 compared to original MCF‐7 cells. In addition, total 89 kinds of Korean edible plant extracts were screened for the inhibitory activity against Nrf2 signaling pathway using an ARE‐luciferase assay system. Among these samples, Chestnut (Castanea crenata) leaf extract dramatically decreased nuclear translocation of Nrf2 and its downstream protein expression of antioxidant enzymes in MCF‐7 CSCs, and also attenuated the resistance to paclitaxel. These findings suggest that Chestnut leaf extract or its constituents could be utilized to increase therapeutic efficacy of anticancer agents through inhibition of Nrf2 signaling pathway.Support or Funding InformationThis study was supported by the National Research Foundation (Grant No. R2014R1A2A2A01005773, funded by the Ministry of Science, ICT and Future Planning; Grant No. 2013R1A1A2013362, funded by the Ministry of Education) Republic of Korea.
The impact of policies to reduce trans fat consumption: A systematic review of the evidence
Authors: Downs Shauna , Bloem Milan , Zheng Miaobing , Catterall Elise , Meertens Beth , Veerman Lennert , Wu Jason 
Published: November 2023

The consumption of industrially produced trans fatty acids (TFA) has been associated with an increased risk of heart disease. In recognition of this, countries, states and cities worldwide have implemented TFA policies (e.g., mandatory or voluntary limits, labeling) aimed at reducing their availability in the food supply. This study builds on a previously published review that examined the impact of TFA policies worldwide from 2000–2013. A systematic literature search of the peer reviewed and grey literature was conducted to identify additional studies examining the impact of TFA policies published between 2013 and 2016. Studies that were: 1) empirical, 2) examined a TFA policy and 3) examined the effect of the policy on TFA levels/availability pre and post policy intervention were included. Modelling studies examining the impact of TFA policies were also included. A total of 13 studies published between 2013 and 2016 were included in the review, including seven modelling and six studies examining ‘real world’ TFA policies. Overall, the modelling studies indicated that TFA bans would reduce heart disease risk, would benefit socioeconomically disadvantaged populations the most and would be cost saving. The ‘real world’ TFA policy studies all reported reductions in TFA. When combined with the findings of the previous review which included a total of 15 studies, there is strong evidence to suggest that mandatory TFA bans lead to the largest reductions in TFA levels and that whilst labelling policies also lead to reductions in TFA levels/intakes additional progress could still be made given that high levels of TFA remain in some products. The combined studies also show that reformulation of products to reduce TFA has had variable effects on saturated fat levels in these foods – in some cases saturated fat levels increased, in others they decreased and for some products they remained the same. Policies aimed at reducing TFA in the food supply are effective and will likely reduce the burden of diet‐related disease, particularly among the most vulnerable socioeconomic groups. Moving forward, national, regional or global approaches to reducing TFA should be adopted in order to further reduce the levels of TFA in the food supply.Support or Funding InformationNational Heart Foundation of Australia