bluuebunny/crossref_metadata_2025_split huggingface dataset:
The mitohormetic response and an evaluation of a method for inducing oxidative damage
Authors: Zhang Yufeng , Humes Frances , Brasher Adam , Kavazis Andreas , Hood Wendy 
Published: June 2021

It has been proposed that mitochondria display a biphasic response to reactive oxygen species (ROS) accumulation referred to as mitohormesis. Under mitohormesis, low levels of ROS stimulate protection against oxidative damage, whereas high levels result in the accumulation of oxidative damage. The mechanisms that underlie improved function following low levels of ROS production are poorly understood. We evaluated the changes in mitochondrial performance in house mice following X‐irradiation, which induces ROS production. Eight mice were maintained as unexposed controls and 8 mice were assigned to each of 5 groups that varied in time between x‐ray exposure and mitochondrial isolation, including 1 hour, 1, 4, 7, and 10 days after x‐ray. We measured mitochondrial respiratory function (RCR), ROS production (H2O2), and oxidative lipid damage (4‐HNE) in the liver and the skeletal muscle from both hind legs and liver. In liver, RCR showed a right skewed U‐shape curve in which day 1 and day 4 mice had significantly lower RCR than both non‐irradiation control, and all other x‐rayed mice. H2O2 and 4‐HNE in liver displayed inverse U‐shaped curves, with both peaking on day 4. Similar trends that were not significant were observe for RCR, H2O2 and 4‐HNE levels in muscle. These data provide evidence that mitochondria become damaged in response to x‐ray, but recover within one week of exposure. This represents the protective effect that ROS exposure has on mitochondrial function. Ongoing measurements of oxidative damage repair, mitophagy, mitochondrial apoptosis, and biogenesis will provide more comprehensive understanding of the mitohormetic response. The value of x‐ray in inducing oxidative damage in experimental studies will be discussed.Support or Funding InformationThis research was funded by US National Science Foundation grant 1453784
RNA‐seq Analysis of the Effects of Cold‐Acclimation and Freezing on the Hepatic Transcriptome in the Freeze‐Tolerant Cope's Gray Treefrog, Hyla chrysoscelis
Authors: do Amaral M. Clara F. , Frisbie James , Goldstein David L. , Krane Carissa 
Published: June 2021

Cope's gray treefrog, Hyla chrysoscelis, is one of few freeze‐tolerant amphibians found in North America. This species is able to withstand freezing of its body fluids, partly by accumulating two cryoprotective compounds putatively synthesized by the liver: glycerol and glucose. Extracellular glycerol accumulates during cold acclimation, whereas somatic freezing triggers hepatic release of glucose, likely through glycogen catabolism. In this study we investigated how cold acclimation and freezing modulated hepatic gene expression in H. chrysoscelis. We hypothesized that pathways related to cryoprotectant production and stress tolerance would be upregulated to meet the physiological challenges encountered by these frogs during fall and winter. We generated a hepatic transcriptome using high‐throughput RNA sequencing and compared gene expression profiles among frogs that were warm‐acclimated, cold‐acclimated, and frozen. Sequences were annotated using Trinotate and Blast2GO, and the R package DESeq 2 was used to determine differential gene expression between treatments. We annotated approximately 34% of the transcriptome. Cold‐acclimated and frozen animals had more downregulated genes than upregulated. Contrary to expectation, expression of genes related to glycerol synthesis was unchanged from warm to cold conditions. Furthermore, glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) showed decreased expression in cold and frozen animals, suggesting a reduction in either gluconeogenic flux, glycolysis or both, which may impact cryoprotectant accumulation. On the other hand, glucose export from the liver may be promoted in both cold and frozen frogs as glucose‐6‐phosphatase (G6Pase) was upregulated in these conditions. However, glucose transporters 8 (GLUT8) and 10 (GLUT10), the sodium/glucose cotransporter 4 (SGLT4), and the glycerol channel aquaporin 9 (AQP9) were downregulated in frozen frogs, raising questions regarding the export of hepatic glucose and glycerol during freezing. Several genes involved in protein folding (e.g., heat shock proteins) and DNA repair were upregulated in cold and frozen frogs, although pro‐apoptosis genes were both up‐ and downregulated, whereas genes related to mitigating oxidative stress were downregulated in these groups. These results warrant further investigation of the different types of cellular insult that may be present in the liver during fall and winter. Our results suggest that hepatic genes are highly responsive to low temperatures. Furthermore, we found that control of cryoprotectant production and export, and of stress‐related gene expression, is in part accomplished by regulating transcription.Support or Funding InformationSupported by NSF IOS‐1121457 to CMK and DLG, Schuellein Chair in the Biological Sciences to CMK, and Schuellein Chair Postdoctoral Fellowship to MCFA.
Bicarbonate‐Stimulated Soluble Adenylyl Cyclase Is an Acid‐Base Sensor Present in the Cell Cytoplasm and Nucleus of Elasmobranch Fishes
Authors: Roa Jinae N , Tresguerres Martin 
Published: June 2021

Regulation of acid‐base stress (i.e. carbon dioxide [CO2], pH, and bicarbonate [HCO3−]) is essential for proper functioning of cells, organs, and whole‐animals; however, the mechanisms for sensing acid‐base stress are largely unknown in marine animals. One such sensing mechanism involves the evolutionarily conserved acid‐base sensor soluble adenylyl cyclase (sAC, adcy10), which is present and co‐expressed along with transmembrane adenylyl cyclases (tmACs, adcy1–9) in leopard shark and round ray acid‐base regulatory gill cells. Both sAC and tmACs produce the second messenger cyclic adenosine monophosphate (cAMP), but have different regulatory effects depending on species and tissue type. In isolated base‐secreting cells exposed to alkalosis, HCO3− activation of sAC led to translocation of the proton pump to the cell membrane, whereas forskolin activation of tmACs did not. Additionally, sAC is present in other shark tissues including the rectal gland, cornea, intestine, and white muscle where it likely regulates acid‐base status in response to tissue‐specific physiological acid‐base disturbances. Furthermore, sAC is present in the cell nucleus where it likely facilitates regulation of gene expression through protein kinase A (PKA) phosphorylation of target proteins.Support or Funding InformationJNR is supported by the William Townsend Porter Pre‐doctoral Fellowship from the American Physiological Society. This research was supported by NIH Training Grant in Marine Biotechnology (GM067550) to JNR and NSF grant IOS 1354181 to MT
Role of an Abscisic Acid‐Activated Protein Kinase in Drought Response in Soybean Revealed by RNA‐Seq
Authors: Sah Saroj Kumar , Popescu George , Reddy K. Raja , Klink Vincent , Li Jiaxu 
Published: June 2021

Glycine max (soybean) is the most important oilseed cereal crop, most widely grown in the world. It is the most important source of protein and oils for humans as well as for biodiesel production. Drought stress is the major environmental factor limiting the productivity of soybean. With the rapid growth of global population and environmental degradation, improving soybean yield is a crucial task to meet the human demand for food and energy. Soybean can survive drought stress if there is a robust and deep root system. Thus, there is a significant need for crop improvements that will increase stress tolerance. Abscisic acid is the essential hormone mediating abiotic stress responses in plants. We previously identified an abscisic acid‐activated protein kinase (AAPK) in broad bean and demonstrated that AAPK is a positive regulator that can enhance abscisic acid signaling. These results suggest that genetic engineering of the AAPK gene may have the potential to improve drought stress in crop plants. To this end, we have generated overexpression and RNAi lines of three AAPK homologous genes in soybean. We found an RNAi line of AAPK homologous gene a noticeable reduction in plant wilting in response to drought treatment. To understand the phenotype changes of this AAPK‐knockdown line, we conducted a genome‐wide transcriptomic analysis in roots of soybean at the early vegetative stage under drought stress. The analysis with an RNA‐Seq pipeline (using STAR aligner and edgeR analysis of differential gene expression) identified over 4000 gene transcripts that were differentially expressed as a response to drought stress in wild‐type samples and RNAi knockdown samples. Our ongoing study reveals the dynamic transcriptomic reconfiguration in soybean roots to acclimate drought stress and highlights the gene expression changes associated with signaling through AAPK. We expect that pathway analysis of the differentially expressed genes will reveal new signaling components associated with drought stress in soybean.Support or Funding InformationThis research was supported by MAFES (Mississippi Agricultural and Forestry Experiment Station) Special Research Initiative grants to Jiaxu Li and Vincent Klink. Saroj Sah is supported by a MAFES Director's Doctoral Fellowship awarded to Jiaxu Li and Raja Reddy. This material is based upon work that is supported by the National Institute of Food and Agriculture, U.S. Department of Agriculture, Hatch/Multi State project (Multistate No. NC1200; Project No. MIS‐153180) under Accession No. 232044. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture.
Rosehip (Rosa canina) extracts prevent AKT and MAPK‐mediated cell proliferation in triple negative breast cancer cells
Authors: Cagle Patrice , Martin Patrick 
Published: June 2021

Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, characterized by its lack of the human epidermal growth factor receptor‐2, the estrogen receptor, and the progesterone receptor. AKT and MAPK have been shown to promote cell proliferation and migration in triple negative breast cancer. Currently, the existing targeted therapy is of minimal benefit in TNBCs. Furthermore, adverse side effects and the emergence of drug‐resistant cancer cells are of great concern. Natural products have received growing interest in recent years as an alternative medicine with potential anti‐oncogenic properties. Rosehip extracts have been used as dietary supplements to relieve symptoms associated with gastrointestinal disorders and arthritis, and in our laboratory it has been shown to prevent cell proliferation in glioblastomas. This study investigated the efficacy of rosehip extracts in preventing proliferation of a triple negative breast cancer cell line (HCC1395). HCC1395 cells treated with rosehip extracts (1mg/mL–25ng/mL) demonstrated a significant decrease in cell proliferation. The observed decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when inhibitors of the MAPK (U0126, 10 μM) or AKT (LY294002, 20 μM) signaling pathways were utilized. Additionally, pretreatment of this cell line with rosehip extracts selectively decreased AKT, p70S6K, and MAPK phosphorylation suggesting these extracts prevent TNBC cell proliferation and migration by blocking the AKT and MAPK signaling mechanisms. Western blot analysis and apoptosis studies demonstrate that rosehip extracts inhibit cell proliferation without promoting apoptosis, but induce cell cycle arrest.To investigate the potential clinical application of rosehip extracts we examined whether rosehip extracts could enhance the chemotherapeutic properties of Doxorubicin (20μM), a chemotherapeutic agent used to treat breast cancer. Rosehip extracts demonstrated a greater anti‐proliferative effect than Doxorubicin alone and is equally effective in combination with Doxorubicin. These data suggest that rosehip extracts are capable of decreasing cell proliferation in a triple negative breast cancer cell line by blocking the AKT and MAPK signaling pathways and by regulating the cell cycle. Moreover, rosehip extracts demonstrate a greater inhibition of cell proliferation, when given alone and combination with Doxorubicin. This investigation demonstrates that rosehip extracts may serve as either an alternative or complimentary treatment to current chemotherapeutic regimens for triple negative breast cancer.Support or Funding InformationNational Science Foundation Graduate Research Fellowship Program Grant No. (NSF 13‐085)
New formulations for fortified‐blended foods: the MFFAPP Tanzania efficacy trial
Authors: Delimont Nicole M , Alavi Sajid , Lindshield Brian 
Published: June 2021

BackgroundFortified‐blended foods (FBFs) are micronutrient fortified, partially precooked blends of cereals and pulses that are the most commonly distributed micronutrient‐fortified food aid globally. Along with reformulation to improve FBF quality, it has been suggested that alternative commodities like sorghum and cowpea be considered for FBF formulation due to their drought tolerance, and local and regional availability in food aid receiving regions.ObjectivesOur primary objective was to determine whether newly formulated, extruded corn, soy, sorghum and cowpea‐based FBFs would result in equivalent or better hemoglobin and anemia outcomes compared with CSB+, the most commonly distributed FBF by the United States Agency for International Development. Secondary outcomes included evaluation of anthropometric and z‐score changes in height, weight, and mid‐upper arm circumference among groups.MethodsTwenty‐week, partially randomized cluster control trial located in the Mara region of Tanzania between February and July 2016. White sorghum cowpea (WSC‐1, WSC‐2), red sorghum‐cowpea (RSC), white sorghum‐soy (WSS), extruded corn‐soy blend (CSB14), or CSB+ were provided to 2186 children divided into two age groups (6–23 and 24–53 months) in seven clusters. A negative control received no FBF until study end. At 0, 10, and 20 weeks, health questionnaires, hemoglobin, and anthropometric measurements were collected. Anemia prevalence, height, weight, MUAC, WAZ, LAZ, and WHZ were calculated for each cluster at each time point. Differences in baseline socioeconomic factors, food intake and unadjusted outcomes were analyzed with SAS. Absolute anemia risk reduction was calculated for all FBFs and control compared to CSB+. Improvement and deterioration in HAZ and LAZ were also analyzed.ResultsNewly formulated FBFs were non‐inferior, or superior, to CSB+ in all outcome measures. At end line, there were significant absolute anemia risk reductions in all newly formulated FBFs compared to CSB+ in at least one age group; CSB14 and WSC‐1 anemia prevalence was significantly reduced in both age groups. In both groups, there were significant improvements in control, WSC‐2, and WSS consuming groups' HAZ scores from baseline to end line, and more children's HAZ scores improved than deteriorated compared to control in all FBFs groups.ConclusionResults suggest that sorghum and cowpea may be suitable alternatives to corn‐soy based FBFs. Socioeconomic and health factors will be analyzed in adjusted models for all outcomes.Support or Funding InformationUnited States Department of Agriculture (USDA) Foreign Agricultural Service under the Micronutrient Fortified Food Aid Products Pilot (MFFAPP) program, contract number #FFE‐621‐2012/033‐00.
Content Validity of the Abbreviated Women's Empowerment in Agriculture Index (A‐WEAI) in Ethiopia: A Mixed Methods Approach
Authors: Min‐Barron Marion , Coates Jennifer , Ghosh Shibani , Rogers Beatrice , Maluccio John 
Published: June 2021

The conceptual pathway between agriculture and nutrition through the vehicle of women's empowerment has garnered much attention as a means to reducing global malnutrition. Until recently, understanding this complex pathway was particularly challenging given that there was no widely accepted approach to measuring women's empowerment. In 2012, Feed the Future launched the Women's Empowerment in Agriculture Index (WEAI), which measures the empowerment, inclusion and agency of women within the agricultural sector. This research study assessed the internal validity of the Abbreviated Women's Empowerment in Agriculture Index (A‐WEAI), a second iteration of the WEAI, within the context of Ethiopian smallholder farming households. Through three phases of data collection, this study identified salient aspects of Ethiopian culture and social gender norms that influence the reliability and internal validity of the A‐WEAI as an indicator of Ethiopian women's empowerment. The first phase entailed 24 focus groups, which collected qualitative data on Ethiopian agricultural households' gender norms and understanding of the term ‘women's empowerment’. Within the second phase, 300 households responded to the quantitative A‐WEAI survey. These results were used to test content validity through principal component analysis and internal reliability through Cronbach's alpha. The last phase of data collection further assessed content validity through an expert panel survey that was used to construct a Content Validity Index (CVI). Results indicate that there are distinct Ethiopian gender norms in relation to agricultural engagement. Women most commonly defined ‘empowerment’ to mean ‘decision‐making’ and cited relationships to others (spouses, children, extended family, etc) as a strong influence on perceived levels of empowerment. To the best of our knowledge, neither the WEAI nor A‐WEAI has been assessed for content validity in any setting. Results from this study hold great significance as they contribute to understanding, for the first time, the content validity of the scale in general. This study also provides insights into the A‐WEAI's functioning in Ethiopia. Future research is needed to identify specific appropriate changes to the A‐WEAI such that women's empowerment is measured in an accurate, valid (both internally and externally) and reliable manner and thus useful in guiding policy.Support or Funding InformationThis research work was made possible by the support of the American people through the United States Agency for International Development (USAID) under Agreement No. AID‐663‐A‐11‐000‐17. The contents of this document are the sole responsibility of the researcher & do not necessarily reflect the views of USAID or the United States Government.
Avocado Consumption and Risk Factors of Heart Disease: a Systematic Review and Meta‐analysis
Authors: Mahmassani Hiya , Avendano Esther E , Raman Gowri , Johnson Elizabeth J 
Published: June 2021

BackgroundAvocados contain a variety of nutrients and phytochemicals that have individually been related to cardiovascular benefit.ObjectiveTo summarize the data related to avocado consumption (whole fruit, oil) and risk for cardiovascular diseases (CVD) using systematic review and meta‐analysis.DesignMedline, Cochrane Central, and CAB databases were searched through October 2016 for all language publications on avocado intake and heart health indices. We included studies of all designs that quantified the amount of avocado intake in adults. CVD risk factors of interest included serum lipids, blood pressure, body weight, blood glucose and insulin levels, inflammatory markers, and all clinical outcomes of CVD. Studies were eligible if participants were healthy or if cardiovascular risk factors such as obesity, dyslipidemia, diabetes, or hypertension were present at baseline. The minimum duration of follow‐up for blood lipid outcomes was set at 3 weeks.Two investigators independently screened citations and extracted data. Random effect models meta‐analysis was used when at least 3 studies reported the same outcome.ResultsOf the 17 studies (449 subjects) published between 1960 and October 2016 and eligible for our review, 6 studies reported quantitative data for meta‐analyses of avocado intake versus no avocado intake, 3 studies compared avocado plus other monounsaturated fats intake with a control diet, and 8 studies reported qualitative data. The funding sources included industry (5 studies) and government/academia (5 studies) and were not reported in 7 studies. Avocado intake non‐significantly decreased serum total cholesterol (TC) (6 trials, net change −3.97 mg/dL, 95% CI −9.43, 1.50); LDL‐C (6 trials, net change −4.22 mg/dL, 95% CI −11.32, 2.89); and triglycerides (6 trials, net change −20.69 mg/dL, 95% CI −43.32, 1.94). Avocado intake significantly increased HDL‐C (6 trials, net change 3.17 mg/dL, 95% CI 0.21, 6.13); decreased TC:HDL (4 trials, net change −0.45 (95% CI −0.68, −0.22) and LDL:HDL (3 trials, net change −0.19 (−0.38, −0.01). Body weight was unchanged with avocado intake (5 trials, net change 0.19 mg/dL, 95% CI −0.20, 0.57). The differences in outcomes of blood glucose, HOMA‐IR, BMI, systolic and diastolic blood pressure were reported in <3 studies and were not significant between avocado and control groups. None of the eligible studies reported incident clinical outcomes of CVD.ConclusionReviewed studies of avocado intake were unable to show a statistically significant decrease in serum TC, LDL‐C and triglycerides levels. However, avocado intake significantly increased serum HDL‐C levels and consequently decreased TC:HDL ratio and LDL:HDL ratio, indicating a potential association between avocado intake and reduced CVD risk.Support or Funding InformationThis study was supported by the Hass Avocado Board and USDA 1950‐51000‐087
Potential Effects of javamide‐I found in coffee on inflammatory chemokine MCP‐1 in rats fed a high fat diet.
Authors: Park Jae 
Published: June 2021

Javamide‐I is a phenolic amide found in coffee with potential health effects. Monocyte chemoattractant protein‐1 (MCP‐1) is a well‐known chemokine and its reduction is considered beneficial in suppressing the pathophysiological progression of cardiovascular, kidney and other diseases, commonly found in the obese. Therefore, in this paper, we investigated javamide‐I as a potential p38 MAP kinase inhibitor, because the kinase is critically involved in the expression of MCP‐1. At the concentration of 20 μM, javamide‐I significantly inhibited p38 MAP kinase alpha, beta, gamma and delta by 15–50% (P < 0.05), particularly p38 MAP kinase alpha (IC50 = 19.2 μM) and beta (IC50 =19.5 μM). We also found that monocytic THP‐1 cells treated with javamide‐I (10, 20 and 40 μM) led to significant inhibition of MCP‐1 production by 17–49% (P < 0.05) in the cells, suggesting that javamide‐I may decrease MCP‐1 expression via inhibiting p38 MAP kinase. Due to the positive in vitro data, the potential effect of javamide‐I on MCP‐1 expression was also investigated in an obesity‐induced rat model. For this study, animals were divided into three groups (n=10): a normal control diet (C), a high fat diet (HF), or a high fat diet supplemented with javamide‐I (2 mg per day) (HFS). After 16 weeks, blood samples were collected from the animals in each group and the plasma levels of MCP‐1 protein were determined. As expected, the average MCP‐1 level of the HFS group was significantly lower than that of the HF group (P < 0.05), although the average MCP‐1 level of the HF group was found to be higher than that of the C group (P < 0.05). In summary, the data suggest that javamide‐I found in coffee may inhibit MCP‐1 expression, possibly via inhibiting p38 MAP kinase and its supplementation could suppress plasma MCP‐1 expression critically involved in several inflammatory diseases.Support or Funding InformationUSDA (1235‐51000‐054‐00D)