bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substrate recognition in lysine deacetylases (769.7)
Authors: Toro Tasha , Painter Richard , Garrett Destane , Watt Terry 
Published: June 2021

Protein acetylation is a widely used cell signaling mechanism which reversibly regulates many cellular processes. Lysine deacetylases (KDACs) catalyze the hydrolysis of ε‐N‐acetyl lysine residues to generate an unmodified lysine and acetate. Perturbations in this process have been linked to diseases, including cancer and inflammation. Thousands of acetylated proteins have been identified, but little is known about how proteins are deacetylated. We aim to understand how individual KDACs recognize their preferred substrates. Assays performed using standard commercial reagents and acetylated peptides as substrates suggest that KDACs and their variants have unique specificity profiles. To better understand this in a biologically relevant context, we have engineered model proteins which more closely resemble natural KDAC substrates. Each is a fixed scaffold that contains a single acetylated lysine in a defined variable sequence and secondary structure. Binding and activity for KDAC‐substrate pairs are used to determine KDAC substrate preference and specificity. By combining these results with structural data and molecular modeling, we will gain insights into the mechanism of KDAC substrate recognition.Grant Funding Source: Supported by Louisiana Cancer Research Consortium, NIH #8G12MD007595‐05, DoD W911NF‐13‐1‐0129
Qualitative evaluation of barriers to appropriate gestational weight gain among participants in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) (807.3)
Authors: Kim Loan , Koleilat Maria , Whaley Shannon 
Published: June 2021

Although recent numbers show a slowing or a leveling off of obesity rates in US, the current high rate of obesity is still a cause for great concern. Women of reproductive age who are low‐income are particularly vulnerable for becoming obese because of excessive gestational weight gain (GWG) and failing to lose the weight after delivery. In 2009 the Institute of Medicine revised its 1990 recommendations and released new GWG recommendations. Our formative study was designed to examine challenges and barriers women experience in maintaining appropriate weight gain during pregnancy. We conducted eight focus groups with a total of 45 Latina, white and black pregnant women (ages 18‐45) in the WIC program. Focus group interviews were designed to elicit culturally relevant information about how best to adapt evidence‐based intervention approaches to assist WIC participants to gain weight within IOM weight gain guidelines. We will present salient elements for adapting the IOM guidelines to develop, pilot and evaluate a generalizable and sustainable intervention to prevent excessive GWG among WIC participants in Southern California.Grant Funding Source: USDA
Calculation of total meal δ13C from individual food δ13C (813.2)
Authors: Casperson Shanon , Schoeller Dale , Johnson LuAnn , Whigham Leah 
Published: June 2021

Variations in the isotopic signature of carbon in biological samples can be used to distinguish dietary patterns and monitor shifts in metabolism. But for these variations to have meaning, the isotopic signature of the diet must be known. We sought to determine if knowledge of the 13C isotopic abundance (δ13C) of individual foods can be used to reliably calculate the δ13C of a mixed meal. Aliquots of 60 individual foods and 21 meals comprised of those foods were freeze‐dried, ground, weighed, and analyzed using an isotope ratio mass spectrometer. The δ13C of the individual foods were then used to calculate the δ13C of meals comprised of those foods and compared to the analyzed δ13C of the corresponding meal. The calculation was weighted such that the contribution of individual foods to the isotopic signature of the meal was relative to the caloric contribution of the food item to the total caloric content of the meal. The measured δ13C (‐23.76‰) and calculated δ13C (‐23.72‰) of the meals did not differ (‐0.04‰, 95% CI = ‐0.30 to 0.22‰) with limits of agreement (+/‐ 2SD) of ‐1.20 ‐ 1.12‰, and the difference was not dependent upon the magnitude of the δ13C by Bland‐Altman regression (slope = ‐0.17, p = 0.88). In conclusion, approximation of the isotopic signature of whole meals can easily and accurately be calculated when the analysis of each meal is not feasible. These results will aid in the characterization of individual dietary intake.Grant Funding Source: Supported by he United State Department of Agriculture, Agricultural Research Service
A novel method for detecting dietary (and other) toxicities: quantifying the adverse effects of added sugar consumption (814.8)
Authors: Ruff James , Hugentobler Sara , Suchy Amanda , Sosa Mirtha , Tanner Ruth , Morrison Linda , Gieng Sin , Shigenaga Mark , Potts Wayne 
Published: June 2021

The ultimate function of an organism’s physiology is the performance of complex behaviors that facilitate reproduction. Here we use Organismal Performance Assays (OPAs) to quantify declines in Darwinian fitness of house mice due to experimental exposures. OPAs are sensitive phenotyping approaches that use semi‐natural conditions to challenge the physiology of differentially treated animals in direct competition with each other. Using OPAs we demonstrated that consumption of human‐relevant levels of added sugar (25% kcal) decreases reproduction of male mice by 25% while doubling the mortality rate of females relative to starch‐fed controls. Furthermore, we showed that many clinical measures associated with proximate effects of added sugar consumption were not predictive of organismal‐level effects. We expand upon these studies by using OPAs to test for differential health consequences of the two most common forms of added sugar. We report that females fed a diet containing an equal ratio of fructose and glucose monosaccharides (modeling high fructose corn syrup; HFCS) experienced a mortality rate 1.9 times higher and produced 26% fewer offspring than those fed sucrose (fructose‐glucose disaccharide). This experiment provides evidence that fructose and glucose monosaccharides (HFCS) are more deleterious to mammalian health than isocaloric sucrose.Grant Funding Source: Supported by NIH and NSF
Mouse embryonic stem cell differentiation into cardiomyocytes is inhibited by ethanol but only after the embryoid body stage (844.3)
Authors: DeKrey Gregory , Worley Jones Sarah , Terry Alex , Gardiner Catherine , Vaughn Brittney 
Published: June 2021

Ethanol up to 0.5% is recommended for use as a solvent in mouse embryonic stem cell (mESC) differentiation assays such as the Embryonic Stem Cell Test. However, lower concentrations have been shown by some to alter mESC differentiation. In this study, we further explored the dose‐ and time‐dependent affects of ethanol on mESC differentiation into cardiomyocytes using the hanging drop culture method and J1 mESC. Among control cultures (no ethanol), rhythmically contracting cells were observed in cultures after 11 days at a frequency of 蠅64%. With continuous ethanol exposure, a significant (p 蠄 0.05) decrease in the fraction of cultures containing contracting cells was observed by 蠅68% at ethanol concentrations of 0.3% and higher and was accompanied by a 蠅30% loss of cells. With ethanol exposure during the first two days of culture only (the embryoid body stage), no significant change in the frequency of contracting cells per culture, or number of cells, was observed after 11 days at ethanol concentrations up to 0.5%. These results suggest that ethanol concentrations below 0.5% can reduce the frequency of contracting cells, at least in part, by reducing the number of cells during differentiation, and that the most sensitive time‐frame for ethanol toxicity is after the embryoid body stage.Grant Funding Source: Supported by NSF DUE‐0622421
Understanding variation in salt sensitivity in HumMod, a human physiological simulator (857.11)
Authors: Pruett William , Husband Leland , Hester Robert 
Published: June 2021

Understanding variation between humans is a critical step in maximizing the efficiency of clinical trials. We studied the chronic blood pressure response to salt loading in a population of virtual patients created in HumMod, an integrative mathematical model of human physiology. Patients differed in the parameterization of their cardiovascular and renal systems. Baseline mean pressure was 96±6 at an intake of 180 mmol Na+/day, and after one week of 250 mmol Na+/day, mean pressure was 96±6.6. 10% of individuals experienced pressure increase of more than 8 mmHg over this period, with the greatest increase measuring 23 mmHg. Sensitivity analysis confirmed that the individual correlates of chronic resting blood pressure differed from those of salt loading hypertension. Chronic pressure was affected more by the loop of Henle and distal tubule, and the efferent arteriolar resistance. Salt‐sensitivity was located in the proximal tubule, the afferent arteriole, and ANP production. Renin production was important in both cases. Sensitivity analysis confirmed that no single factor was uniquely responsible for salt sensitivity, indicating model robustness. Rather salt sensitivity represents a confluence of small divergences whose combined effect reaches physiological significance. Used in this way, the model represents a powerful tool for analyzing pooled effects and their impact on variance in human populations.Grant Funding Source: Supported by NSF EPS‐090378 and NIH HL‐51971
Blood lactate accumulation in forced submerged turtles that can and cannot shunt (879.11)
Authors: Rana Rahul , Williams Cassondra , Hicks James 
Published: June 2021

Freshwater turtles are capable of remaining underwater for over four months. This is in part due to their ability to reduce their metabolism in order to survive long periods of anoxia. Another unique ability freshwater turtles possess is the ability to shunt blood, or cause blood to deviate from the normal cardiovascular circuit due to pulmonary and vascular resistance changes. Although the functional significance of cardiac shunting is not well understood, one hypothesis for its function is that hypoxemia, induced by cardiac shunting, causes a reduction in metabolism. To test this hypothesis, levels of blood lactate, a product of anaerobic metabolism, were measured in animals that could and could not shunt. Atropine was given to the turtles to eliminate the ability to shunt. Higher blood lactate levels in turtles that cannot shunt would support the relationship between cardiac shunting and reduced metabolism. Red‐eared sliders were anesthetized and surgically fitted with catheters inserted into a blood vessel in the neck. The turtles were forcibly submerged for one hour. Blood samples were taken through the catheter. Alternatively, blood samples were collected from the tail vein before and after the submersion. Preliminary data showed no difference in lactate levels between turtles that can shunt and those that cannot. Lactate data were also analyzed to determine the aerobic dive limit (ADL) during forced submersions. The ADL is the duration of a submergence at which a significant increase in blood lactate concentration is observed. Results suggest turtles that were capable of shunting had an ADL falling between 20‐30 minutes.Grant Funding Source: Supported by NSF (1121324‐IOS)
Changes in tracheal system structure and function within an instar in the caterpillar, Manduca sexta (879.23)
Authors: Greenlee Kendra , Pedersen Paul , Back Barbarah 
Published: June 2021

Juvenile grasshoppers and caterpillars are less tolerant of hypoxia as they grow between molts. One possible explanation is that substantial soft tissue growth occurs between molts, compressing the tracheal system when the exoskeleton can expand no further. In grasshoppers, femoral air sacs become compressed, as they age between molts. Juvenile insects periodically molt their exoskeletons to enable the expansion of larger cuticular structures within. Respiratory structures are part of the exoskeleton and must also molt to grow larger. However, the mechanism for the decrease in hypoxia tolerance in caterpillars is unknown. To test the hypothesis that the caterpillar tracheal system becomes compressed during the intermolt period (instar), we used synchrotron x‐ray imaging to record tracheal system structure and function. Caterpillars at the beginning and end of each instar were placed in 21% and 1% oxygen. Maximum and minimum diameters of two major tracheae, one in the head and one in the hind segment were measured, along with body size and mass. Body mass and length increased logarithmically from hatchling to fifth instar, while head width increased only when insects molted. Maximum tracheal diameter also increased after molting, most significantly from the fourth to the fifth instar. In support of our hypothesis, both minimum and maximum tracheal diameters varied with stage differently depending on the instar. Minimum tracheal diameter decreased depending on the instar, because only older caterpillars exhibit tracheal compression in hypoxia. In older instars, head tracheae were larger than hind tracheae. In addition, in contrast to our previous work, tracheae in both the head and hind segments scaled with mass to the 0.3 power. Together, these data demonstrate that the decreased hypoxia tolerance within an instar is due to the fixed size of major tracheae and provide a comprehensive view of how the caterpillar respiratory system changes in structure and function within an instar.Grant Funding Source: Supported by NSF IOS 0953297
Deep‐diving sea lions exhibit extreme bradycardia in long‐duration dives (879.3)
Authors: McDonald Birgitte , Ponganis Paul 
Published: June 2021

Heart rate and peripheral blood flow distribution are the primary determinants of the rate and pattern of oxygen store utilization and ultimately breath‐hold duration. We investigated dive heart rate (ƒH) in five California sea lions (Zalophus californianus) during maternal foraging trips by instrumenting them with digital electrocardiogram (ECG) loggers and time depth recorders. In all dives, dive ƒH (50 ± 9, range 28‐81 beats min‐1) decreased compared to surface rates (113 ± 5 beats min‐1), with all dives exhibiting an instantaneous ƒH below resting (<54 beats min‐1). Typical instantaneous ƒH profiles of deep dives consisted of 1) an initial rapid decline in ƒH resulting in the lowest instantaneous ƒH of the dive at the end of descent, often below 10 beats min‐1, 2) a slight increase in ƒH during the bottom portion of the dive, 3) a gradual increase in ƒH during ascent with a rapid increase prior to surfacing. Extreme bradycardia and the associated reductions in pulmonary and peripheral blood flow during late descent of deep dives should a) contribute to preservation of the lung O2 store, b) increase dependence of muscle on the myoglobin‐bound O2 store, c) conserve the blood O2 store, and d) help limit the absorption of N2 at depth. This ƒH profile during deep dives of sea lions may be characteristic of deep‐diving higher vertebrates that dive on inspiration.Grant Funding Source: Supported by the Office of Naval Research
The conserved SKN‐1/Nrf antioxidant response has complex interactions with the heat shock response (880.4)
Authors: Tang Lanlan , Choe Keith 
Published: June 2021

Numerous inducible gene pathways have been defined as coordinating defense and repair in response to one of many types of stress. A major challenge now is to begin understanding how these pathways interact to optimize homeostasis, mitigate competition for common substrates, and avoid incompatibilities. In animals ranging from nematodes to mammals, the transcription factor SKN‐1/Nrf controls the expression of over 50 detoxification and antioxidation genes in response to oxidants and electrophiles. Surprisingly, we find that while SKN‐1/Nrf activity is beneficial for survival of oxidants and reactive small molecules, it is strongly detrimental to survival of heat stress. Genome‐wide chromatin‐immunoprecipitation and microarray data from the genetic model Caenorhabditis elegans suggest that SKN‐1/Nrf negatively regulates several genes within the heat shock response, including heat‐shock transcription factor 1 (HSF‐1). We also find that high temperature has complex effects on the SKN‐1/Nrf pathway; it causes accumulation of the factor in the nucleus, but interferes with induction of many target genes. Therefore, our early work suggests that there may be multiple interactions between conserved responses to oxidants and heat that influence signaling and functional outcomes of both pathways.Grant Funding Source: NSF grant IOS‐1120130
AltitudeOmics: pulmonary gas exchange efficiency in humans with and without a PFO following 16 days of acclimatization to 5,260 m (885.2)
Authors: Elliott Jonathan , Laurie Steven , Goodman Randall , Beasley Kara , Kern Julia , Subudhi Andrew , Roach Robert , Lovering Andrew 
Published: June 2021

A PFO is a source of intracardiac shunt causing impaired pulmonary gas exchange efficiency, defined by an increased alveolar‐to‐arterial PO2 difference (AaDO2). Prior studies investigating human acclimatization to high altitude (HA) have not investigated differences between subjects with a patent foramen ovale (PFO+) and those without (PFO−), yet prevalence of PFO in the general population is ~40%. Twenty‐one (11 PFO+) healthy lowlanders were studied at rest and at 70, 100, 130, and 160W of cycle ergometer exercise at sea level (SL), in acute hypoxia at 5,260 m (ALT1), and after 16 days of acclimatization to 5,260 m (ALT16). Exercise data were compared at the highest iso‐workload, within an individual, achieved at SL, ALT1 and ALT16. During exercise at SL, PFO+ subjects demonstrated a wider AaDO2 compared to PFO− subjects, however on ALT1 the AaDO2 was not different between PFO− and PFO+ subjects. At ALT16, unlike PFO− subjects, AaDO2 in PFO+ subjects was not different from ALT1. Surprisingly, at ALT16 the PFO+ group did not demonstrate an increase in resting minute ventilation and consequently, did not increase either alveolar PO2 or arterial PO2 relative to ALT1. Taken together, our data suggest that 1) intracardiac shunt in PFO+ subjects results in significantly worse pulmonary gas exchange efficiency after acclimatization to HA and 2) these subjects demonstrate physiological changes consistent with a reduced ability to acclimatize to HA.Grant Funding Source: Supported by: Department of Defense #W81XWH‐11‐2‐0040
Hypoxia augments intracellular hydrogen sulfide in LPS‐stimulated murine macrophages (888.3)
Authors: DeLeon Eric , Olson Kenneth 
Published: June 2021

Hydrogen sulfide (H2S) is an important signaling molecule, yet it has been technically difficult to measure H2S production, metabolism or distribution at the cellular and sub‐cellular level in tissue. As H2S has been implicated in hypoxic signaling, we hypothesized that H2S produced during an induced inflammatory response would be augmented under hypoxic conditions. Intracellular H2S production was monitored via silicate nanoparticles, PEBBLEs (Photonic Explorers for Bioanalysis with Biologically Localized Embedding). PEBBLES were synthesized with a hydrophilic core that traps fluorescein mercuric acetate (FMA), an analyte‐sensitive dye that becomes irreversibly quenched when bound to sulfur moieties, and a hydrophobic shell permeable to small lipophilic molecules, such as H2S. FMA‐loaded PEBBLES are thus able to provide a historical account of intracellular H2S production. Murine bone marrow‐derived macrophages (BMDM) avidly ingest PEBBLES (BMDM+P) and remain viable as determined by confocal microscopy for an extended period (72 h). Cells incubated in normoxic conditions and treated with Lipopolysaccharide (LPS) showed a slight decrease in fluorescence intensity above the control over 48hrs, which could be blocked by the pre‐treatment with aminooxyacetic acid (AOA) and proparglycine (PPG). However, cells incubated in hypoxic conditions showed much larger decreases in fluorescence intensity, particularly when pre‐treated with LPS, and were less affected by the inhibitors. This supports the hypothesis that LPS stimulates H2S production in BMDM and that this is considerably augmented by hypoxia.Grant Funding Source: Supported by NSF DGE‐1313583 (ERD) and NSF IOS‐1051627 (KRO)
The effects of high fat diet to alter glucose‐induced modulation of 5‐HT3 receptor responses in GI‐vagal afferents is reversible (905.3)
Authors: Troy Amanda , Browning Kirsteen 
Published: June 2021

5‐hydroxytryptamine (5‐HT) released from enterochromaffin cells activates gastrointestinal (GI) vagal afferent neurons. Previous studies in this lab have shown that (i) glucose modulates this 5‐HT induced response and (ii) that relatively short periods of exposure to a high fat diet (HFD) disrupt this glucose dependent modulation. The aim of this study was to investigate the reversibility of this loss of glucose modulation.Sprague‐Dawley rats were placed on HFD (60% kcal from fat) for 3 days. Thereafter, normal chow was restored (18% kcal from fat). Nodose ganglia were removed and 5‐HT3 receptor (5‐HT3R) distribution was assessed in acutely dissociated GI‐projecting vagal afferent neurons following exposure (30min) to different glucose concentrations (1.25‐20mM).The ability of glucose to traffic 5‐HT3Rs was restored after 2 weeks recovery on control diet although earlier timepoints showed no recovery. Specifically, after 2 weeks recovery on control diet, the relationship between extracellular glucose concentration and membrane‐associated 5‐HT3R density was linear, ranging from 27.8% in 1.25mM to 33.9% in 20mM (n=19‐22; p<0.05 vs earlier timepoints; P>0.05 vs no HFD exposure). These results suggest that while the effects of HFD exposure are reversible, the time course of recovery is much longer than the initial exposure period.Grant Funding Source: NIH DK078364, NSF IOS1148978
Modeling the epigenetic influence of climate on upper respiratory tract proportions with two groups of Macaca mulatta (918.12)
Authors: Pagano Anthony , Laitman Jeffrey 
Published: June 2021

Many studies have focused on population differences in upper respiratory tract (URT) morphology and evolutionary adaptation to climate. However, epigenetic influence of local climate on cranial development has not received much attention. This study used two samples of adult male Macaca mulatta raised in outdoor colonies in California (n=7; CA, a warmer climate) and Oregon (n=8; OR, a colder climate). Postmortem whole heads underwent CT and three‐dimensional landmark coordinate data were collected from axial slices for Generalized Procrustes Analysis. This showed a measurement artifact constrained to Principal Component 1 (PC1; roughly 60% of shape variance) with much overlap between CA and OR groups in PC2 (10.4%). However, they tended to separate on PC 3 (7.38%), on which OR specimens exhibited longer nasal roofs, taller and narrower choanae, narrower piriform apertures, increased length and angulation of the cartilaginous Eustachian tube, shorter basicrania, and less external basicranial flexion and facial kyphosis. Centroid size was larger (p<0.0009) among the OR sample but body weight was higher among the CA group (p<0.024), suggesting a larger URT relative to body size in the colder habitat. Results indicate that local climate may exert subtle epigenetic influence on URT morphology, warranting further study.Grant Funding Source: National Science Foundation