bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between serum leptin, iron status, and dietary iron intake in young adults
Authors: McClung James P. , Lutz Laura J. , Hennigar Stephen R. , Karl J. Philip , Cable Sonya J. , Cropper Thomas L. , Gaffney‐Stomberg Erin 
Published: June 2021

Leptin,a hormone secreted by adipose tissue, is a regulator of energy intake and expenditure. Iron, an essential micronutrient, functions as a cofactor for proteins and enzymes involved inoxygen transport and energy metabolism. Dietary iron intake and adipocyte iron levels have been recently demonstrated to suppress leptin expression in animals. Additionally, recent studies indicate aninverse association between serum leptin and serum ferritin (SF) in humans, independent of body mass. However, associations between iron status and serum leptin have not been examined in healthy young adults. As such, the objective of this study was to explore relationships between serum leptin, iron status indicators (SF, soluble transferrin receptor[sTfR], transferrin saturation [TS], hemoglobin, and hepcidin), and dietaryiron intake in young adults (n = 513, males = 306, females = 207, age[mean ± SE] = 20.6 ± 0.1 yrs, body fat = 17.4 ± 0.5 %). Biomarkers were assessed in blood from fasted volunteers; dietary iron intake was assessed using food frequency questionnaires. Univariate line arregression indicated negative correlations (P < 0.05) between serum leptin and SF (r = −0.26), TS (r = −0.21), hemoglobin (r = −0.36), and hepcidin (r =−0.09), and a positive association (P < 0.05) between serum leptin and sTfR(r = 0.10). In fully adjusted (age, body fat percentage, inflammation, and race) linear regression models, serum leptin and hemoglobin were positively associated (P < 0.05) in men (β ± SE = 0.07 ±0.02), but not women (β = 0.01 ± 0.02), whereas serum leptin and dietary iron intake were negatively associated (P < 0.05) in men (β = −0.53 ± 0.24), but not women (β = 0.25 ± 0.21). Associations between serum leptin and other iron status indicators were not statistically significant in either sex in fully adjusted models. Taken together, these data suggest that associations between serum leptin, iron status, and dietary iron intake are not independent of body fatness in young adults. Future studies conducted in large cohorts with individuals with varying body composition are required to elucidate the potential link between iron status and appetite regulation.Support or Funding InformationResearch supported by USAMRMC.
Amelioration of Cardiometabolic Risk Factors With a Pecan‐rich Diet in Overweight and Obese Adults
Authors: McKay Diane L. , Eliasziw Misha , Chen C‐Y Oliver , Blumberg Jeffrey B. 
Published: June 2021

Evidence from in vitro and observational studies indicates tree nuts may reduce the risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus (T2DM), though support from controlled feeding trials is limited. Most nut intervention studies to date have counseled subjects to incorporate nuts into their usual diet, an approach that can neither control for inter‐individual variability in the background diet, nor fully account for the intake of other food/beverage components that can influence CVD and T2DM risk, e.g., antioxidants, fatty acids, and fiber. We conducted a 12 wk randomized, controlled, cross‐over feeding trial to examine the effects of pecans in overweight and obese men and postmenopausal women ≥45 y with central adiposity. Subjects (n=25) were randomized to either a diet resembling the average American diet (control) or the same diet with whole pecans (intervention) incorporated at ~15% of energy (1.5 oz/2000 kcal) for 4 wk, and then the opposite diet for the final 4 wk. Total fat and fiber in these isocaloric diets were similar, and all meals/snacks were provided. During the 2 wk run‐in and 4 wk washout periods, subjects were counseled to consume the control diet. A multivariate multilevel model was used to simultaneously analyze change in z‐scores of insulin, glucose, total cholesterol, triglycerides, and LDL. An interim analysis (n=18) yielded a mean increase of 0.11 SD in the control arm and a decrease of 0.23 SD in the intervention arm (mean difference between arms = 0.34 SD, P=0.047). Although differences in favor of the intervention arm were observed for all individual cardiometabolic risk factors, the sample size was too small for them to reach statistical significance. Preliminary evidence suggests a pecan‐rich diet may have a benefit in modifying cardiometabolic risk factors.Support or Funding InformationSupported by USDA and the National Pecan Shellers Association
Effectiveness of the Compensatory Reserve Index in Monitoring Blood Resuscitation in Baboons
Authors: Hinojosa‐Laborde Carmen , Nguyen Betty , Mulligan Jane , Grudic Greg , Convertino Victor 
Published: June 2021

BACKGROUNDThe Compensatory Reserve Index (CRI) is a machine learning algorithm that detects the body's ability to compensate for blood loss by analysing changes in arterial waveforms. Previous studies have shown CRI to be more accurate than traditional vital signs in estimating an individual's risk of hemodynamic decompensation. However, the effectiveness of the CRI in monitoring volume resuscitation has not been evaluated. The purpose of this study is to assess the ability of CRI to detect volume resuscitation incomparison to traditional vital signs.METHODSThis study compared systolic arterial pressure (SAP), heart rate (HR), stroke volume (SV), and CRI during whole blood resuscitation after 25% blood volume hemorrhage in baboons (n=12). The study was conducted at the Texas Biomedical Research Institute (San Antonio, TX)under an approved protocol by their Animal Care and Use Committee. Statistical analysis was performed using two repeated measures ANOVA and linear regression analysis.RESULTSSV, SAP, HR, and CRI were all sensitive to blood resuscitation. SV and SAP overshot baseline during resuscitation, but CRI did not. Target SAP for resuscitation is 80–90 mm Hg. The corresponding CRI value was approximately 0.25–0.30, which aligns with the transition from an unstable to a moderately compromised condition.CONCLUSIONSCRI can detect not only hemorrhage, but also blood resuscitation in baboons. CRI is equally effective as traditional vital signs for detecting blood resuscitation. The ease of tracking CRI makes it a potentially effective clinical tool for monitoring blood resuscitation.Support or Funding InformationFUNDING: US Army Medical Research and Materiel Command Combat Casualty Care Research Program
Predicting salt and diuretic sensitivity in a virtual population using topological data analysis
Authors: Clemmer John S. , Pruett W. Andrew , Hester Robert L. 
Published: June 2021

Salt sensitivity, with or without concomitant hypertension, is associated with increased mortality. In the clinical setting, determining salt‐sensitivity in patients is laborious and an expensive challenge with low patient compliance. A large subset of salt‐sensitive patients with hypertension are known to be resistant to diuretic therapy. Personalized medicine distinguishes specific subpopulations to better manage individual patients, but this concept has not been adequately applied to the treatment of hypertension. We hypothesized that topological data analysis (TDA) of physiological responses to salt loading in a computer‐generated cohort can predict patient salt‐sensitivity and responses to thiazide therapy. Using HumMod, an integrative mathematical model of human physiology, we studied the chronic blood pressure response to salt loading (500 mMol/day for 2 weeks) in a heterogeneous population of 4000 virtual patients created by varying cardiovascular and renal system parameters. A binned clustering algorithm distinguished salt‐sensitive ( >6 mmHg change in blood pressure after salt loading) and salt‐insensitive patient populations. One cluster of patients in the salt‐sensitive population, characterized by lower plasma sodium and glomerular filtration rate at baseline, had significantly greater fall in blood pressure in response to thiazide administration (−5.6±0.2 vs. −4.5±0.2 mmHg) which was associated with a blunted activation of the renin‐angiotensin system. We also determined that following an acute water loading simulation, urine volumes and salt output correlate with physiological sensitivity to high salt intake and diuretic therapy. This data suggests that TDA of physiological behavior in human populations could be used as a predictive tool and improve personalized medical treatment.Support or Funding InformationSupported by the National Science Foundation under Grant No. NSF EPS‐0903787 and the NIH P01 HL 51971.
Effects of Tolvaptan on Mechanosensory Primary Cilia
Authors: Sherpa Rinzhin T , Nauli Surya M 
Published: June 2021

Primary cilia are non‐motile sensory extensions present in a variety of cells. Over the past decades, studies have shown to associate the pathology of polycystic kidney disease (PKD) to defective in mechanosensory primary cilia (ciliopathy). We have previously shown that improving cilia length can enhance mechanosensory cilia function, which we termed “ciliotherapy”. Because tolvaptan is seen to be a potential therapy in PKD, we tested the hypothesis that tolvaptan can alter cilia length or function. In the present study, mouse and porcine renal tubule cells were grown to confluent monolayer. Once differentiated, tolvaptan was added to culture plates to achieve desired concentrations. Cilia length and function were measured with standard microscopy techniques using acetylated‐α‐tubulin and Fura‐2AM, respectively. Tolvaptan at 0.1 μM optimally increased cilia length and function. Cell cycle analysis showed no significant differences between control and tolvaptan treated cells. In summary, our studies indicate that tolvaptan may have a positive therapeutic effect on cilia function.Support or Funding InformationDepartment of Defense (PR130153)
An Experimental Test of Colony Size Effects on Mass‐Specific Metabolic Rate in a Social Insect
Authors: Waters James S , Ochs Alison , Toth Jack , Fewell Jennifer H. , Harrison Jon F. 
Published: June 2021

The metabolic costs of being an organism generally scale hypometrically, such that per‐gram metabolic rates decrease with increasing size. The drivers of this almost universal feature have yet to be clearly identified. Cohesive social groups, particularly the social insects, also show hypometric scaling with colony size. It is not known whether size is a causal factor or whether this relationship is only a correlation. We experimentally reduced the size of harvester ant colonies (Pogonomyrmex californicus), to test whether colony size is causally responsible for large colonies utilizing less energy per gram. We identified three potential parameters, all related to the organization of the work, that are candidate mechanisms for driving hypometric scaling of metabolism. Larger colonies had lower median (but not average) walking speeds, and more ants classified as stationary, potentially reducing locomotory costs. Larger colonies had reduced mass‐specific perimeters of the brood pile, consistent with reduced per‐capita brood rearing, a potentially expensive task. Finally, larger colonies had reduced network density and centrality, consistent with greater division of labor, specialization, and segregation of individuals, which may reduce metabolic costs by improving efficiency. A simulation model suggests that simple behavioral rules may cause reduced network densities that could reduce colonial metabolic rates by promoting specialization in task performance and activity levels.Support or Funding InformationThis research has been supported by Providence College, the James S. McDonnell Foundation, and the National Science Foundation under Grant No. 1110796.
Doublet Potentiation During In Vitro Cyclical Movement of Mdm Mouse Muscles
Authors: Enright Dory , Monroy Jenna A , Nishikawa Kiisa 
Published: June 2021

It has been observed that the addition of a stimulus (doublet) to a train of stimuli increases the force output of muscles, and that the effect of a doublet on force diminishes as muscle length increases. In natural movements such as running, muscles are activated at various lengths during cyclical motion. Thus, the increase in force due to the addition of a doublet during cyclical movements likely depends on the length at which a muscle is stimulated during the cycle (i.e. phase of activation). Recent work has suggested that the elastic protein, titin, may play a role in doublet potentiation. Using the muscular dystrophy with myositis (mdm) mouse, which is characterized by a deletion in the N2A region of titin, we investigated the role of titin in doublet potentiation during work loop experiments. We measured force output of soleus muscles from wildtype and mdm mice subjected to cyclical changes in length and stimulated at various phases. The length and force data were used to construct work loops, which were integrated to determine the work output of each muscle. Results show that the addition of a doublet increased muscle work at lower stimulation frequencies (p < 0.0001), and that at these same frequencies the relative increase in work was greater in wildtype compared to mdm muscles (p = 0.0003). In addition, both genotypes showed the largest increase in work when stimulated at the shortest lengths, and the smallest increase when stimulated at the longest lengths (p < 0.0001). These interactions between activation and length suggest that elastic elements play a role in doublet potentiation. Our work is consistent with the winding filament hypothesis, which suggests that titin contributes to active muscle force.Support or Funding InformationThis work was funded by the Anderson Endowment at Denison University, an APS UGSRF award to D.E.E., and NSF 1456868.
Maternal High Fat Diet Increases an Inhibitory Extrasynaptic Tonic GABAA Current in Dorsal Motor Nucleus of the Vagus Neurons Regulating Gastric Functions
Authors: McMenamin Caitlin A , Browning Kirsteen N 
Published: June 2021

The perinatal period is critically important in the development of autonomic neurocircuits innervating the gastrointestinal (GI) tract influencing gastric emptying and appetite regulation. Developmental alterations may affect these GI neurocircuits possibly contributing to the energy imbalance seen in obesity. Previous studies suggest there is an increased GABAergic inhibition of gastric projecting dorsal motor nucleus of the vagus nerve (DMV) neurons in the brainstem of rats fed a high fat diet (HFD) during the perinatal period, but the underlying neural mechanisms and the effects on gastric motility have yet to be clarified. The aims of this study was to assess the effects of perinatal HFD on (i) inhibitory synaptic inputs to gastric‐projecting DMV neurons and (ii) gastric tone and motility.Whole cell patch clamp recordings were made from gastric projecting DMV neurons in thin brainstem slices from Sprague‐Dawley rats (4–6 weeks of age) fed either a control or HFD (14 or 60%kcal from fat, respectively) from embryonic day 13.In the present study, perinatal HFD rats were not significantly heavier than age‐matched control rats (6 weeks; 232±17g vs 209±5g). Superfusion with the non‐selective GABAA receptor antagonist, bicuculline (50μM), induced a larger inward current in DMV neurons from perinatal HFD vs control animals (55.7±14.1pA vs 21.7±1.7pA, n=8, P<0.05), suggesting a greater overall tonic inhibition. While superfusion with the phasic (synaptic) GABAA receptor antagonist, gabazine (25μM), did not reveal any difference in the resulting inward current between perinatal HFD vs control DMV neurons (11.2±1.4pA vs 6.7±1.5pA, n=6, P>0.05), the addition of bicuculline into the bath uncovered a larger tonic (extrasynaptic) GABAA current in perinatal HFD vs control DMV neurons (36.4±3.47pA vs 20.8±2.24pA, n=6, P<0.05), suggesting that the greater overall inhibition of perinatal DMV neurons results from a larger tonic GABAA current.The studies imply that perinatal overnutrition increases the tonic GABAergic inhibition of gastric projecting DMV neurons via an increase in activation of extrasynaptic GABAA receptors. Such alterations in brainstem neurocircuit development as a consequence of maternal over‐nutrition may induce gastric dysmotility and dysregulated gastointestinal reflexes, hence influence offspring to develop obesity.Support or Funding InformationFunded by NIH 078364 and NSF IOS1148978
Quantification of javamide‐I and ‐II in twelve coffee drinks and their effects on sirtuin1/2/3 enzymes and p53‐acetylation in THP‐1 cells.
Authors: Park Jae 
Published: June 2021

Coffee is one of most consumed drinks worldwide. Javamide‐I (N‐coumaroyltryptophan) and‐ II (N‐caffeoyltryptophan) are phenolic amides found in coffee. However, the amounts of javamide‐I and‐ II have not been determined in daily consumed coffee drinks, and their effects on sirtuin1/2/3 enzymes are still unknown. Therefore, in this paper, javamide‐I and ‐II were isolated and quantified from coffee using a HPLC method, and their effects on sirtuin1/2/3 enzymes were studied. First, the chemical structures of isolated javamide‐I and‐ II were unambiguously confirmed using NMR spectroscopic methods. Then, their amounts were determined in 12 different coffee samples prepared using five beans, four ground and three instant coffees. Javamide‐I and ‐II were detected in some coffee samples at the ranges of 0.04–2.31 mg/g. Using javamide‐I and ‐II isolated from coffee, their effects on sirtuin1 (nuclear), sirtuin2 (cytoplasm) and sirtuin3 (mitochondria) were investigated in vitro. Javamide‐II showed higher inhibition activity against sirtuin1 (IC50 of 30 μM), 2 (IC50 of 8 μM) and 3(IC50 of 61 μM) than javamide‐I. Especially related to sirtuin2, javamide‐II exhibited noncompetitive inhibition of sirtuin2 with Ki = 9.6 μM. In a docking simulation, javamide‐II showed stronger binding pose to sirtuin2 than EX527. Also, javamide‐II was able to increase total acetylation levels and the acetylation of p53 in monocytic THP‐1 cells. In addition, differential effects of javamide‐I and ‐II analogues on inhibiting sirtuin1/2/3 will be also discussed in this study.Support or Funding InformationUSDA
Maternal Lipid‐based Nutrient Supplements (LNS) Did Not Reduce Depressive Symptoms During Pregnancy and Lactation in Rural Bangladesh
Authors: Matias Susana L , Mridha Malay Kanti , Khan Showkat Ali , Hussain Sohrab , Siddiqui Zakia , Vosti Stephen , Arnold Charles D , Dewey Kathryn G 
Published: June 2021

BackgroundMaternal depression is a major global burden affecting not only women but also their children. Maternal intake and serum levels of polyunsaturated fatty acids have been inconsistently associated with reduced perinatal depression.ObjectiveWe aimed to determine the effects of lipid‐based nutrient supplement (LNS), containing macro and micronutrients, including essential fatty acids (4.6 g of linoleic acid and 0.6 g of alpha‐linolenic acid), on maternal depressive symptoms at 36 weeks of gestation and 6 months postpartum.MethodsWe conducted a cluster‐randomized effectiveness trial in Bangladesh (the Rang‐Din Nutrition Study), where women received either iron & folic acid (IFA) or LNS during pregnancy and the first three or six months postpartum, respectively. Maternal depressive symptoms were assessed by trained interviewers using a validated Bangla version of the Edinburgh Postnatal Depression Scale (EPDS‐B) at 36 weeks of gestation (n=2937) and 6 months postpartum (n=3510) at local antenatal clinics. Outcomes included the EPDS score (range: 0–30) and prevalence of depressive symptoms, defined as an EPDS score ≥10.ResultsOverall median (interquartile range) EPDS scores were 2 (0–4) and 1(0–3) at 36 weeks of gestation and 6 months postpartum, respectively. Prevalence of reported maternal depressive symptoms was low in this population (2.1% at 36 weeks of gestation and 2.7% at 6 months postpartum). Cluster‐adjusted intention‐to‐treat analyses indicated no significant differences by treatment group in EPDS scores (square root back transformed Means ± SEs; 36 weeks of gestation: 1.4 ± 0.1 vs 1.5 ± 0.1 in the LNS and IFA groups, respectively, p=0.22; 6 months postpartum: 1.2 ± 0.1 vs 1.3 ± 0.1 in the LNS and IFA groups, respectively, p=0.12) or prevalence of depressive symptoms (36 weeks of gestation: 2.5% in the LNS and 2.0% in the IFA group, p=0.42; 6 months postpartum: 2.8% in the LNS and 2.6% in the IFA group, p=0.68). Per‐protocol analysis including only those who consumed the supplements regularly indicated lower EPDS scores in the LNS compared to the IFA group at 36 weeks of gestation (1.2 ± 0.1 vs 1.5 ± 0.1, respectively, p=0.01). No other significant differences by treatment group were observed in per‐protocol results.ConclusionIn Bangladesh, maternal LNS did not show an effect on reported depressive symptoms in late pregnancy and at 6 months postpartum. Reports of depressive symptoms in this population were less common than in other populations in Bangladesh, which may have limited our ability to detect effects of LNS.Support or Funding InformationU.S. Agency for International Development (USAID)'s Food and Nutrition Technical Assistance (FANTA) III Project, managed by FHI 360.
Regulation Of Homologous Recombination: Robustness Through Reversibility
Authors: Heyer Wolf‐Dietrich 
Published: June 2021

Homologous recombination is a critical pathway to maintain genome stability. The signature reactions in recombination of homology search and DNA strand invasion are carefully regulated. The Rad51‐ssDNA filament, which conducts the homology search, exists in a balance between assembly and disassembly, where specific motor proteins, such as Srs2 in yeast, lead to disassembly of the filament. This process reverses Rad51 filament formation as a mechanism of anti‐recombination. A second mechanism of anti‐recombination is the disruption of the primary DNA strand invasion product, the nascent D‐loop. While it has been thought that the disruption of D‐loops is being conducted by motor proteins and helicases, we showed that nascent D‐loop dissolution by Top3‐Rmi1 represents a distinct mechanism of anti‐recombination. Another level of regulation affects the outcome of recombination, the formation of crossover or non‐crossover products. The Synthesis‐Dependent Strand Annealing (SDSA) pathway of DNA double‐strand break repair envisions the disruption of the extended D‐loop after DNA synthesis to enable the annealing of the extended invading strand with the second end of the double strand break. Hence, different enzymes are needed to target the nascent D‐loop and the extended D‐loop to achieve anti‐recombination or anti‐crossover (= pro‐SDSA), respectively.The model that homologous recombination proceeds as a pathway of successive metastable reversible intermediates has an interesting genetic implication that provides an additional mechanistic explanation for synthetic lethality between mutations in different genes. Eliminating forward and backwards steps in a single reversible pathway simultaneously may lead to trapping of a toxic intermediate or depletion of an essential compound. Such genetic interactions have been observed in the recombination pathway and are likely applicable to additional reversible pathways.Support or Funding InformationWe are grateful for the funding from the National Institutes of Health and the Department of Defense.