bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global patterns in copepod thermal tolerance
Authors: Sasaki Matthew , Dam Hans G 
Published: June 2021

AbstractCopepods are key components of aquatic habitats across the globe. Understanding how they respond to warming is important for predicting the effects of climate change on aquatic communities. Lethal thermal limits may play an important role in determining responses to warming. Thermal tolerance can vary over several different spatial and temporal scales, but we still lack a fundamental understanding of what drives the evolution of these patterns in copepods. In this Horizons piece, we provide a synthesis of global patterns in copepod thermal tolerance and potential acclimatory capacities. Copepod thermal tolerance increases with maximum annual temperature. We also find that the effects of phenotypic plasticity on thermal tolerance are negatively related to the magnitude of thermal tolerance, suggesting a potential trade-off between these traits. Our ability to fully describe these patterns is limited, however, by a lack of spatial, temporal and phylogenetic coverage in copepod thermal tolerance data. We indicate several priority areas for future work on copepod thermal tolerance, and accompanying suggestions regarding experimental design and methodology.
A MRG-operated chromatin switch at SOC1 attenuates abiotic stress responses during the floral transition
Authors: Barrero-Gil Javier , Mouriz Alfonso , Piqueras Raquel , Salinas Julio , Jarillo José A. , Piñeiro Manuel 
Published: June 2021

Abstract
Plants react to environmental challenges by integrating external cues with endogenous signals to optimize survival and reproductive success. However, the mechanisms underlying this integration remain obscure. While stress conditions are known to impact plant development, how developmental transitions influence responses to adverse conditions has not been addressed. Here, we reveal a molecular mechanism of stress response attenuation during the onset of flowering in Arabidopsis (Arabidopsis thaliana). We show that Arabidopsis MORF-RELATED GENE (MRG) proteins, components of the NuA4 histone acetyltransferase complex that bind trimethylated-lysine 36 in histone H3 (H3K36me3), function as a chromatin switch on the floral integrator SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) to coordinate flowering initiation with plant responsiveness to hostile environments. MRG proteins are required to activate SOC1 expression during flowering induction by promoting histone H4 acetylation. In turn, SOC1 represses a broad array of genes that mediate abiotic stress responses. We propose that during the transition from vegetative to reproductive growth, the MRG-SOC1 module constitutes a central hub in a mechanism that tunes down stress responses to enhance the reproductive success and plant fitness at the expense of costly efforts for adaptation to challenging environments.
ANALYSIS OF HAND EXPOSURE AMONG NUCLEAR MEDICINE TECHNOLOGISTS IN SAUDI ARABIA
Authors: Alashban Yazeed , Shubayr Nasser 
Published: June 2021

Abstract
The increase in the amount of radioactive materials administered to patients as well as the number of procedures performed has focused attention on the issue of radiation exposure to the hands of workers in nuclear medicine departments worldwide. The study aims to estimate the equivalent doses to the hands of individuals in nuclear medicine departments in Saudi. A cross-sectional analysis was conducted for 404 annual dose records in 16 nuclear medicine departments from 2016 to 2019. The monitoring of individual doses to the hands was performed using a Harshaw ring dosemeters. During the study period, the average annual equivalent doses per handled activity ranged from 0.21 to 0.41 μSv/GBq. The estimated annual activities of radiopharmaceuticals ranged from 2 to 930 MBq per exam. The hand dose averaged over the 4-year study period was determined to be 1.81 ± 0.25 mSv. The collective annual hand dose increased by 265% from 2016 to 2019.
Characterization of Ion Channels in Progenitor Cells Isolated From CTEPH Patients
Authors: Firth Amy L. , Platoshyn Oleksandr , Cancino Eric , Yuan Jason X.‐J. 
Published: June 2021

The cellular and molecular mechanisms contributing to the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) remain poorly understood. This study characterizes ion channels present in multipotent mesenchymal progenitor cells (MPC) isolated from endarterectomized tissue from patients with CTEPH. A population of myofibroblast‐like cells expressing MPC markers (CD29, CD44, CD73, CD90, CD105, CD166) was identified. These cells formed CUF‐F‐like colonies and were capable of adipogenic, myogenic and osteogenic differentiation. Whole‐cell patch clamp technique was used to isolate K+, Ca2+ and nonselective cation currents (NSCC). Four kinetically different voltage‐dependent K+ currents (Kv) were recorded and inhibited by 4‐AP and TEA. In the absence of extracellular Ca2+, IBTX‐sensitive BKCa currents were detected at membrane potentials >+40mV. Many cells exhibited large NSCC, sensitive to H+ and La3+, but relatively insensitive to 2‐APB and niflumic acid, with a linear current‐voltage relationship reversing at 0 mV. No voltage‐dependent Ca2+ currents were detected. Enhanced expression and oscillatory activity of the Na+‐Ca2+ exchanger (NCX) was observed. The electrophysiological profile of these MPC may suggest a novel pathway for elevation of intracellular Ca2+. Large NSCC may elevate cytosolic Na+, activating the reverse mode NCX to further increase Ca2+ and contribute to remodeling of the pulmonary arteries in CTEPH patients.Funding source: NIH/NHLBI and CIRM Postdoctoral Fellowship
Sodium Dicarboxylate Transporters in Placental Cells
Authors: Hering‐Smith Kathleen S , Coleman‐Barnett Joycelynn , Yu Miao , Abdulnour‐Nakhoul Solange , Hamm L Lee 
Published: June 2021

Placental cells express a number of transporters of metabolic substrates. To determine the presence and regulation of dicarboxylate transporters, we used an established human placental cell line, JAR. NaDC1 and −3 are respectively low and high affinity dicarboxylate transporters most studied on the apical and basolateral membranes of renal proximal tubule and intestinal cells.Both NaDC1 and −3 were present in JAR cells by immunohistochemistry and immunobloting; in the latter, patterns and levels were similar to cultured kidney cells. In JAR cells, 14C‐succinate (Succ) uptake averaged 5.1 ± 0.1 pMol/well and increased to 6.3 ± 0.2 (p < 0.05) by lowering Ca2+ to μM levels. Succ uptake was also stimulated (to 6.5 ± 0.2) by exposure to an acid media (pH ~ 7.1) for 48 h; Succ transport after acidosis was not Ca2+ sensitive. 14C‐Citrate (Cit) transport averaged 6.9 ± 0.5 but was not stimulated by either condition. Substrate affinities for Succ and Cit were relatively low, more consistent with NaDC1 than NaDC3.The stimulation of Succ but not Cit transport by acute reduction in extracellular Ca2+ or prolonged acid media contrasts with prior findings of ours with several kidney cell lines. The complex pattern of regulation suggests the presence of multiple dicarboxylate transporters in these cells with distinct regulation. In conclusion, placental cells contain both NaDC1 and −3, and transport Succ and Cit, but with distinct patterns of regulation. Because Cit complexes Ca2+, regulation of Cit transport could be involved in the placental calcification which occurs late in pregnancy. Funding VA, NIH.
Effects of bilateral inhibition of retrotrapezoid nucleus on breathing in conscious rats
Authors: Takakura Ana C , Moreira Thiago S , de Paula Patricia M , Menani Jose V , Colombari Eduardo 
Published: June 2021

The last five years many studies suggested the retrotrapezoid nucleus (RTN) as the central respiratory chemoreceptors, however all experiments were performed in anesthetized animals. In the present study we sought to investigate a possible role of RTN neurons in the normal breathing in conscious rats. Male Holtzman rats (280–300 g) with bilateral stainless steel cannulas implanted into the RTN were used. In conscious rats, bilateral inhibition of RTN neurons with the GABA‐A agonist muscimol (100 pmol/50 nl) reduced resting ventilation (120±62, vs. saline: 928±77 ml/min/kg) and the increase in ventilation produced by hyperoxic hypercapnia (10% CO2) (962±174, vs. saline: 2654±231 ml/min/kg). However, muscimol into the RTN did not change the increase in ventilation produced by activation of peripheral chemoreceptors with hypoxia (8% O2) (1294±116, vs. saline: 1552±108 ml/min/kg). Bilateral injections of muscimol into the RTN slightly reduced resting MAP (Δ = −13±7, vs. saline: +3±2 mmHg), but did not affect the changes in MAP and HR produced by hyperoxia hypercapnia and peripheral chemoreceptor stimulation. In conclusion, RTN neurons activated by pCO2 presumably via their intrinsic chemosensitivity, provide chemical drive to breathe during resting or hypercapnia.Financial support: FAPESP and CNPq.
High muscle triglyceride content in obesity is not due to elevated lipogenic enzyme activity or to the suppression of lipolytic proteins
Authors: Li Minghua , Paran Christopher , Wolins Nathan E , Horowitz Jeffrey F 
Published: June 2021

We compared key factors that regulate intramyocellular triglyceride (IMTG) metabolism and IMTG trafficking between obese (OB) and lean (LN) women. Skeletal muscle biopsy samples from 8 OB and 9 LN women (BMI: 38±1 and 23±1kg/m2) were obtained after an overnight fast. Despite a nearly 2‐fold greater IMTG concentration in OB vs LN (75±15 vs 40±8 umol/g dw; p<0.05), we found protein abundance of the IMTG synthetic enzyme diacylglycerol acyltransferase 1 (DGAT1) to be lower in OB (p<0.01), with a similar trend for a lower DGAT activity in OB (370±47 vs 441±57 pmol/min/mg; p=0.18). Neither the protein level nor activity of the glycerol‐3‐phosphate acyltransferase (GPAT) was different between groups. We found no differences between groups in muscle adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL) protein abundance, and no differences in phosphorylation of specific sites known to affect HSL activity. Protein abundances of the IMTG trafficking proteins perilipin 2 and 3 were lower (p<0.05) in muscle from OB vs LN when expressed relative to IMTG content. Our findings indicate that the elevated IMTG content found in obese women was not due to an up‐regulation of key lipogenic proteins, or to the suppression of lipolytic proteins. The impact of lower levels of IMTG trafficking perilipins remains to be clarified.Supported by NIH Grant #R01 DK071955
Oxidative stress enhances myofibrillar protein degradation via calpain and caspase‐3
Authors: Smuder Ashley J , Kavazis Andreas N , Hudson Matthew B , Nelson W Bradley , Powers Scott K 
Published: June 2021

Oxidative stress has been shown to accelerate proteolysis and muscle fiber atrophy during periods of prolonged skeletal muscle inactivity. Currently, the mechanisms connecting oxidative stress to muscle protein degradation remain unknown. In this regard, calpain and caspase‐3 are proteases capable of degrading select myofilament proteins in skeletal muscle. However, it is unclear if oxidation of myofibrillar proteins increases recognition and degradation by these key proteases. Therefore, we tested the hypothesis that oxidative modification of myofibrillar proteins increases their susceptibility to degradation by calpain and caspase‐3. Myofibrillar proteins were isolated from skeletal muscle and exposed to in vitro oxidation to produce varying levels of protein modification. Modified proteins were then independently incubated with active calpain I, calpain II, or caspase‐3 and protein degradation was assessed via peptide mapping. Our results reveal that increased protein oxidation results in a stepwise escalation in the degradation of myofibrillar proteins by calpain I, calpain II, and caspase‐3. These findings provide a link to connect oxidative stress with accelerated proteolysis during disuse muscle atrophy.Supported by NIH RO1 HL087839 awarded to SKP
β‐Catenin mediates TGF‐β1‐induced myofibroblast differentiation in a matrix stiffness‐dependent manner: implication to aortic valve sclerosis
Authors: Chen Jan‐Hung , Chen Wen Li Kelly , Sider Krista , Simmons Craig 
Published: June 2021

IntroductionIn aortic valve sclerosis, myofibroblast differentiation and activation of the TGF‐ß1 and ß‐catenin pathways are observed in the fibrosa, the stiffer layer of the leaflet.ObjectivesTo investigate the roles of ß‐catenin and matrix stiffness in TGF‐ß1‐induced myofibroblast differentiation.MethodsSclerotic aortic valves were from pigs fed an atherogenic diet. Porcine aortic valve interstitial cells (VICs) were studied in vitro on collagen‐coated polyacrylamide gels with tunable stiffness.ResultsIn sclerotic valves, myofibroblasts colocalized with TGF‐ß1, Wnt3a, ß‐catenin, and pSmad2/3 in the fibrosa, which was significantly stiffer than the ventricularis (P=0.006). TGF‐ß1 induced pSmad2/3‐dependent ß‐catenin nuclear translocation in VICs more readily on matrices with fibrosa‐like stiffness (P<0.05). Degrading ß‐catenin pharmacologically inhibited TGF‐ß1‐induced myofibroblast differentiation (P=0.04) without altering pSmad2/3 activity. Conversely, increasing ß‐catenin stability with Wnt3a alone did not induce differentiation (P=0.73). However, combining TGF‐ß1 and Wnt3a caused greater myofibroblast differentiation than TGF‐ß1 treatment alone (P=0.004). These novel results suggest that myofibroblast differentiation in valve sclerosis involves matrix stiffness‐dependent cross‐talk between TGF‐ß1 and Wnt signaling pathways.Support: HSFO, NSERC.
Function of Angiostatin in Acute Lung Inflammation
Authors: Aulakh Gurpreet Kaur , Liu Lixin , Suri Sarabjeet Singh , Singh Baljit 
Published: June 2021

ALI is characterized by the migration of activated neutrophils into lungs and causes significant mortality. Although necessary, activated neutrophils also cause significant tissue damage. The mechanisms of neutrophils migration and pathogenesis of ALI are not fully understood. Angiostatin binds to ATP synthase and integrins, and inhibits angiogenesis. We investigated effect of subcutaneous administration of angiostatin in a mouse model of E. coli lipopolysaccharide (LPS) induced ALI. Immunohistochemistry showed higher expression of angiostatin/plasminogen in the airways and blood vessels in the inflamed lungs. Angiostatin expression was increased in inflamed lung extracts as well as bronchoalveolar lavage (BAL) supernatant (P<0.007). Angiostatin treatment of the LPS‐treated mice decreased total cell counts and protein concentration (P<0.05) but increased (P<0.05) apoptotic neutrophils in BAL and decreased (P<0.05) myeloperoxide in lung extracts. The protein and mRNA expression of cytokines and chemokines (IL‐1β, KC, MCP‐1 and MIP‐1α) was not altered in LPS+angiostatin mice. We conclude that angiostatin expression is increased in inflamed lungs and angiostatin treatment inhibits neutrophil migration into the inflamed lungs and lung inflammation. (Funding NSERC Discovery Grant)Grant Funding Source: NSERC Discovery Grant
Medical students using plastinated prosections as a sole learning tool perform equally well on identification exams as compared to those performing dissections over the same regions
Authors: Hoffmann Darren S , May Nikolas , Thomsen Timothy , Holec Megan , Andersen Kathleen H , Pizzimenti Marc A 
Published: June 2021

We sought to determine if small plastinated specimens would be sufficient to replace traditional dissection/prosection methods. A small group of pre‐M1 students (n=26) participated in labs and learned from dissection (D), or plastinated prosections (PP) of body regions/organs. Students who learned the heart from PP performed slightly better on the final identification exam than those who dissected the heart (67.0±6.2 PP vs. 60.3±8.6 D). The exam consisted of tags on both PP and non‐plastinated (NP) hearts. The difference between the groups was due to higher scores from PP students on NP heart tags (70.0±7.2 PP vs. 54.8±8.3 NP). Both groups performed equally on PP heart tags. Other control regions where both groups used the same learning modality had identical scores between groups. To assess differences in learning from PP vs. NP prosections, groups studied the axilla from PP or NP prosections. Students using PP slightly outperformed those learning from traditional NP prosections (51.1±7.9 PP vs. 43.0±6.8 NP). Interestingly, when asked to rank usefulness of the modalities (1–5 Likert scale), students ranked PP significantly lower than D or NP (3.36±0.4 PP vs. 4.36±0.2 NP and 4.46±0.4 D, p<0.05). Reasons ranged from physical properties of the stiffer plastinates to changes in engagement level. These data support use of PP in the medical‐level anatomy curriculum, but student response data indicate limitations.Grant Funding Source: University of Iowa OCRME
Effects of theobromine, a caffeine‐like substance found in cocoa and chocolate, on mood and vigilance
Authors: Judelson Daniel A , Griel Amy E , Miller Debra , Muñoz Colleen X , Kellogg Mark D , Lieberman Harris R 
Published: June 2021

Like caffeine (CAF), theobromine (ThBr) is a methylxanthine found in foods such as cocoa and chocolate that might influence mood. ThBr crosses the blood‐brain barrier and binds to adenosine receptors, suggesting it might share CAF's beneficial effects on mood and vigilance. Therefore, we assessed the effect of ThBr doses commonly found in foods on mood and vigilance parameters sensitive to CAF. CAF was tested as a positive control. Twenty‐four males (age = 23 ± 3 y) completed six double‐blind trials during which they consumed experimental beverages, completed self‐report mood questionnaires, and completed a two hour visual vigilance task. Three experimental beverages (100 mg, 200 mg, and 400 mg ThBr) used a cocoa vehicle; three matched control beverages (0 mg ThBr, 400 mg ThBr, and 100 mg CAF) used a non‐cocoa carrier. Mean salivary [ThBr] exhibited appropriate dose‐dependent differences (400 mg trials > 200 mg trial > 100 mg trial > 0 mg trials, p < 0.05). At every dose tested, ThBr failed to consistently affect mood state or vigilance, but 100 mg CAF expectedly decreased lethargy/fatigue and increased vigor (p < 0.05). These findings indicate ThBr does not influence mood and vigilance when administered in nutritionally‐relevant doses, despite sharing many of CAF's characteristics. Further research is needed to better understand the behavioral effects of cocoa and dark chocolate.Funded by The Hershey Company.
Synergy®, a prebiotic, but not genistein supplementation, either alone or with Synergy®, affects bone mechanical properties in ovariectomized rats
Authors: Legette LeeCole L , Martin Berdine R , Barnes Stephen , Weaver Connie M 
Published: June 2021

Osteoporosis primarily occurs among postmenopausal women, due to age deficiencies in calcium metabolism as well as estrogen‐related bone loss. Prebiotics and phytoestrogens can enhance calcium metabolism and inhibit post‐menopausal bone loss. Recent evidence suggests a combination of prebiotics and phytoestrogen consumption results in greater effects on bone health. A four week feeding study was conducted in 5 mo. old ovariectomized (OVX) Sprague Dawley rats to examine the effect of genistein and genistein + Synergy® (prebiotic) on calcium metabolism and bone health. There were six treatment groups (n=16/group): SHAM Control, OVX Control, OVX rats receiving daily estradiol injections, and OVX rats receiving an AIN 93M diet supplement with either 200 ppm genistein, 5% Synergy®, or 200 ppm genistein + 5% Synergy®. SHAM Control rats had significantly higher femoral bone density, as determined by underwater weighing, than all other OVX groups. A three‐point bending test showed increased bone breaking force (p<0.05) for SHAM Control, OVX rats receiving daily estradiol injections, and OVX rats on 5% Synergy® diet compared to other OVX groups. We conclude that prebiotic (Synergy®) supplementation but not phytoestrogen (genistein) improves bone biomechanical strength in ovariectomized rats.Grant Funding Source: General Mills
Signaling Lessons from Death Receptors
Authors: Dixit Vishva M. 
Published: June 2021

It was thought that receptors signaled either by serving as ion channels or by altering phosphorylation‐dephosphorylation events. Work in my laboratory in the mid‐nineties conclusively showed that death domain‐containing receptors signaled by an entirely new mechanism, specifically, adapter (FADD)‐mediated recruitment and direct activation of a death protease (FLICE/caspase‐8). Subsequent studies by my own and other laboratories showed that this was a universal mechanism deployed by death receptors.Further study of the NF‐kB inducing death receptor, TNFR1, has recently unveiled another new signaling mechanism, that we have termed “ubiquitin editing.” Ubiquitin editing is mediated by a highly conserved single polypeptide protein, termed A20, which contains both a ubiquitin hydrolase and a ubiquitin ligase domain. Initially, this seemed counterintuitive as it was akin to a molecule possessing both kinase and phosphatase activities –– the ultimate futile cycle! We found, however, that these seemingly contradictory activities actually act in concert to attenuate cytokine signaling.
Vitamin D2 enriched mushrooms stimulate innate immunity in LPS challenged rats
Authors: Babu Uma Suresh , Garthoff Larry H. , Calvo Mona S. 
Published: June 2021

Vitamin D (vit D) functions in both innate and acquired immunity. The high prevalence of poor vit D status is due in part to limited intake of naturally rich or vit D‐fortified foods. We exposed white button edible mushrooms to UVB light to markedly increase vit D2 content, creating a naturally rich food source. Our goal was to determine whether the higher vit D2 content of UVB exposed edible mushrooms is bioavailable and functional in modulating innate immune response in rats acutely challenged with lipopolysaccharide (LPS). For 10 wk, 300 weanling female rats were fed 1 of 5 diets, all formulated based on AIN93G to contain: 1) control levels of vit D; 2) no vit D; 3) no vit D +5% unexposed mushroom; 4) no vit D +2.5% UVB exposed mushroom, and 5) no vit D +5% UVB exposed mushroom (Research Diets, New Brunswick, NJ). After vit D analyses, dry powdered mushroom was added at the expense of non‐nutritive fiber. At wk 10, rats were challenged with either saline (control) or LPS and necropsies were performed at 3, 24 and 72 hrs when spleen cells were evaluated for alterations in natural killer cell activity (NK). NK activity was assessed by the standard 51Cr release assay using YAC‐1 cells as target cells and rat splenocytes as the effector cells (1:100 ratio). Independent of the saline or LPS challenge, the NK activity was higher in rats fed the highest level (5%) of vit D enhanced mushrooms when compared to the control fed or vit D deficient diets with 5% unexposed or no mushroom.ConclusionsVitamin D2 from UVB exposed white button mushrooms is bioavailable and effectively functions in innate immunity to stimulate NK activity in a rat model. Source of research support: The Mushroom Council and FDA