bluuebunny/crossref_metadata_2025 huggingface dataset:
The Covid-19 pandemic and its concomitant benefits: improved hygiene habits
Authors: Macaraan Willard Enrique R
Published: June 2021

In an editorial, the editor has explored how state response to the pandemic has collateral damages not only in the public health in general but also in economy and education. Ironically, it also shows that the adjustments and adaptations in peoples’ behavior have resulted in improved habits in personal hygiene and self-care. Not all is bad though as people have (re)learned the basic value of handwashing and preventive measures to avoid any diseases and spread of germs. In the long run, this is going to be beneficial to prevent any repeat of the pandemic of this magnitude.
The environment in the post-pandemic scenario: sustaining the gains
Authors: Macaraan Willard Enrique R
Published: June 2021

In a recent correspondence, the authors noted how temporary the experience of improved air quality in the Philippines during the pandemic. They argued that beyond the crafting of policies and guidelines, there must be a solid attitudinal change in the way a person looks, behaves and lives with his/her surroundings. I support that stance and would further argue that community-based approaches can reinforce that desired change and outcome especially in remote villages and communities where group/communal identity is far more normative than individuated identification.
EVALUATION OF ANNUAL RADIATION EXPOSURE OF STAFF IN A CARDIAC CATHETERIZATION DEPARTMENT IN SAUDI ARABIA
Authors: Sulieman A , Mayhoub F , Ibrahim H Salah , Omer H , Alkhorayef M , Abolaban Fouad A , Al-Mohammed H , Khandaker M U , Bradley D A
Published: June 2021

The objective of this study is to estimate the annual effective dose for cardiologists and nurses by measuring Hp(10) and Hp(0.07) during cardiac catheterization procedures. A total of 16 staffs members were working in interventional cardiology during 1 year at a tertiary hospital. The occupational dose was measured using calibrated thermo-luminescent dosemeters (TLD-100, LiF:Mg,Ti). The overall mean and range of the annual Hp(10) and Hp(0.07) (mSv) for cardiologists were 3.7 (0.13–14.5) and 3.2 (0.21–14.7), respectively. Cardiologists were frequently exposed to higher doses compared with nurses and technologists. The exposure showed wide variations, which depend on occupation and workload. Staff is adhered to radiation protection guidelines regarding shielding the trunk, thyroid shield, thus appropriately protected. Lens dose measurement is recommended to ensure that dose limit is not exceeded.
AI meets narratives: the state and future of research on expectation formation in economics and sociology
Authors: Svetlova Ekaterina
Published: June 2021

This article presents contemporary concepts of economic beliefs in economics and sociology: (a) behavioural accounts; (b) learning; (c) narrative approaches; and (d) Science and Technology Studies-inflected integrative accounts. The review argues that cutting-edge research on expectations in both disciplines has paid insufficient attention to the fact that human agents are supported and partly substituted by modern technology while forming their beliefs. Thus, this article discusses how models, algorithms and artificial intelligence co-determine and profoundly change the theoretical and empirical understanding of expectation formation, and outlines a joint research agenda for studying economic expectations.
Effects of moisture and temperature on Salmonella survivability in beef tallow, white grease, and chicken rendered fat
Authors: Molitor April , Yucel Umut , Vipham Jessie , Jones Cassandra , Trinetta Valentina
Published: June 2021

High moisture levels introduced to fats after the rendering process can lead to Salmonella presence and growth. Limited research on strategies to eliminate pathogens in these environments are available. Rendered fat characteristics, such as water activity and fatty acids composition, may contribute to Salmonella survivability. The purpose of this research was to evaluate the effects of moisture levels (0%, 0.5%, 1%, and 3%), storage temperatures (48 and 76 ˚C), and fat characteristics on the growth and survival of Salmonella in beef tallow, white grease and poultry fat samples. Samples were inoculated with a high (~108 CFU/mL) and a low (~105 CFU/mL) Salmonella cocktail (S. Senftenberg, S. Newport, S. Thompson and S. Infantis). Samples were stored for up to 5 days at 48 and 76 ºC. Remaining population was evaluated daily with and without enrichment step. Death rates were calculated using Weibull model for each temperature and moisture level. Only temperature had an effect (P < 0.05) on Salmonella inactivation, while no effect between moisture and/or inoculum level were observed. When all products were challenged at 76 ˚C, counts were below detectable limits after 6 hours. At 48˚C a progressive decline in Salmonella population was observed within 3 days for both beef tallow and white grease when high inoculum was used for the challenge study. Salmonella was below detectable limit within 4 days for both fat types when a low inoculum was instead applied. This research identified the effect of moisture and temperature in rendered fat samples contaminated with Salmonella and underlined the need to use time–moisture–temperature data to minimize microbial growth during transportation and storage.
Poplar PsnICE1 enhances cold tolerance by binding to different cis-acting elements to improve reactive oxygen species-scavenging capability
Authors: Wang Yan-Min , Zhang Yi-Ming , Zhang Xin , Zhao Xin , Zhang Yu , Wang Chao , Wang Yu-Cheng , Wang Liu-Qiang
Published: June 2021

Low temperature is a major stress that severely affects plant growth and development. Inducer of CBF expression 1 (ICE1) plays a key role in plant cold tolerance by regulating the expression of cold stress-responsive genes. In the present study, we characterized the function and underlying regulatory mechanism of PsnICE1 from Xiaohei poplar (Populus simonii × Populus nigra). PsnICE1 was significantly induced in response to cold stress in the roots, stems and leaves. PsnICE1 proteins were found to localize to the nucleus and exert transactivation activity via their N-terminal transactivation domain. Compared with non-transgenic poplar, transgenic poplar overexpressing PsnICE1 showed substantially enhanced tolerance to cold stress, with higher survival rates and antioxidant enzyme activity levels and reduced reactive oxygen species (ROS) accumulation. In contrast, plants with RNA inhibition-mediated silencing of PsnICE1 showed the opposite phenotype. PsnICE1 can bind to H-box element and abscisic acid-responsive element (ABRE), and more importantly, it mainly binds to IBS1 (a newly discovered cis-acting element) and E-box elements to regulate stress-related genes involved in ROS scavenging. Overall, these results indicated that PsnICE1 functions as a positive regulator of cold tolerance and serves as a potential candidate gene for plant cold tolerance improvement via molecular breeding.
The Use of Eponyms in Education: Ethics, History, and Constructivism
Authors: Barger John Bradley
Published: June 2021

The use of eponyms (personal names used as nouns) in anatomy and medicine has a long and complicated history. Eponyms have been gradually removed from most curricula in favor of descriptive terms as specified in the Terminologica Anatomica. However, a number of eponyms remain in current use, usually given as an alternate term after the preferred term has been defined. I argue that the use of eponyms in normal anatomy and medical curricula should be completely removed. I define three primary arguments for the removal of eponyms. 1. Some eponyms honor scientists who made discoveries through unethical means, notable Nazi scientists in the Third Reich. 2. Many eponyms originated in 18th‐ and 19th‐ century Europe, giving the impression that only male European scientists contributed to the history of medicine. 3. From a pedagogical perspective, eponyms reinforce the misconception that “anatomy is pure memorization.” If we value constructivism and long‐term knowledge retention, systematic names are more valuable to the novice student than the apparently arbitrary eponyms applied to medical and anatomical entities. All of the arguments outlined above are only relevant to the perspective of the anatomy/medical educators. If one is teaching ethics or history of medicine, then the use of eponyms is a great way to highlight the ethical and historical debates necessary to those courses.

Support or Funding Information

None

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Anatomy Observational Outreach: a Multimodal Activity to Enhance Anatomical Education in Undergraduate Students
Authors: Gonzalez‐Sola Maryvi , Hyder Aneesah , Rosario Martin G
Published: June 2021

Undergraduate students often have difficulty relating Anatomy and Physiology (A&P) course contents to their future careers, leading to a lack of interest and degree completion. The purpose of the Anatomy Observational Outreach (AOO) was to raise students' interest in STEM and Allied Health fields, help students make the connection and application between the information presented in A&P labs and real‐world activities, as well as to effectively encourage students to pursue graduate degrees in Allied Health Careers. The outreach consisted of 100 undergraduate A&P students from Texas Woman's University's biology, nursing, kinesiology, health studies, physical therapy, and occupational therapy departments. The methodology consisted of a 15‐minute orientation, graduate student panel Q&A session, 30‐minute cadaver and organ prosections, 30‐minute Anatomage table demonstration, anatomical models, and x‐rays. To measure the impact of the outreach, students were given identical 10‐question pretests and post‐tests, of which each question accounted for 1 point. The results of the students' post‐tests demonstrated a 98% increase in anatomical knowledge and an 84% increase in interest in graduate degrees in STEM and Allied Health fields. Moreover, 81% of students felt all of the activities and tools were useful, while 19% concluded the cadaver prosections were the strongest sole educational aids. It was also found that of the 100 students in attendance, 55% were ethnic minorities and 90% were gender minorities. We conclude that the AOO yielded distinguished results in the depth, retention, and application of A&P knowledge, along with increased interest, excitement, and motivation for pursuing tertiary STEM and Allied Health degrees among undergraduates. The future goal for the AOO is to establish a biannual “Anatomy Week” to encourage and inspire students and minority scholars to further their tertiary education in STEM and Allied Health fields.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Altered Gut Motility in Mice Lacking Neuropilin 2 in Smooth Muscle
Authors: Bielenberg Diane R. , Doyle Claire , Vasquez Evalynn , Pelton Kristine , Cristofaro Vivian , Sullivan Maryrose P. , Adam Rosalyn M.
Published: June 2021

Introduction/Objectives

Profound changes in gut motility and colonic smooth muscle contraction are observed in inflammatory bowel disease states such as colitis. However, the mechanisms that contribute to altered motility and contractility under these circumstances are incompletely defined. Recent data from our group have identified the smooth muscle of the gastrointestinal tract as a major site of expression of neuropilin 2 (Nrp2) in vivo. Nrp2 and the related molecule neuropilin 1 are 130–140 kDa transmembrane receptors for the class 3 semaphorin (SEMA3) family of axonal guidance regulators and for members of the vascular endothelial growth factor (VEGF) family that regulate angiogenesis. Based on recent data from our group implicating Nrp2 as a novel regulator of bladder smooth muscle contractility, the objective of this study was to determine the functional significance of Nrp2 in gastrointestinal smooth muscle.

Methods

Two mouse models were used to explore a role for Nrp2 in gastrointestinal motility: (i) SM22alpha‐Cre; Nrp2 fl/fl mice to enable inducible smooth muscle‐specific deletion of Nrp2 in vivo under controlled conditions and (ii) wild type Balb/c mice exposed to dextran sodium sulfate (DSS) to evoke acute colitis. Gut tissues were subjected to isometric tension testing to characterize contractility. Gut transit was evaluated by charcoal meal assay. Nrp2 levels were assessed by immunohistochemical staining and immunoblot analysis of tissues and of primary colonic smooth muscle cells exposed to inflammatory cytokines.

Results

Smooth muscle‐specific deletion of Nrp2 led to an increase in force generation of colonic rings, upon exposure to electrical field stimulation or treatment with the cholinergic agonist, carbachol. Nrp2 deletion also led to elevated gut transit as assessed by charcoal meal assay. In response to colitis, Nrp2 levels were found to decrease in the distal colon, in parallel with elevated contractility of distal colon rings. In addition, treatment of primary human colonic smooth muscle cells with IL‐4, representative of the TH2 inflammatory milieu associated with DSS colitis, decreased Nrp2 levels while treatment with TNF‐a, characteristic of the TH1 response in colitis increased Nrp2 levels.

Conclusions

These observations suggest that dynamic alterations in Nrp2 under conditions of inflammation may underlie altered contractility of intestinal smooth muscle, resulting in dysmotility. Moreover, these findings suggest that Nrp2 may represent a novel therapeutic target for restoration of normal gut motility.

Support or Funding Information

Harvard Digestive Diseases Center P&F Grant (RMA); R01 DK104641 (RMA, DRB, MPS)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Methocinnamox: Sustained Antagonism of the Antinociceptive Effects of Morphine and Not Spiradoline in Rats
Authors: Gerak Lisa R , Latham Elizabeth A , Woods James H , Disney Alex , Husbands Stephen M , France Charles P
Published: June 2021

The opioid epidemic continues in the US. Currently available pharmacotherapies for opioid abuse and overdose include mu opioid receptor agonists (methadone and buprenorphine) and antagonists (naltrexone and naloxone), and while each treatment can be effective, they have limitations. A novel mu opioid receptor antagonist, methocinnamox (MCAM), has a long duration of action in blocking the abuse‐related and toxic effects of opioids, and its antagonist effects are not surmounted by subsequent administration of mu opioid receptor agonists. Consequently, MCAM might overcome the limitations of other antagonists, although other problems could emerge with long‐term blockade of mu opioid receptors (e.g. prescription opioids would be ineffective for treating pain). The current study measured antinociception using a warm water tail withdrawal procedure in rats and examined the persistence, surmountability, and selectivity of antagonism by MCAM. In 1 group of 8 rats, morphine dose‐effect curves were determined 1 day after MCAM administration and periodically thereafter, and in a different group of 8 rats, a dose‐effect curve for the kappa opioid receptor agonist spiradoline was determined 1 day after MCAM administration with morphine dose‐effect curves determined periodically thereafter. Morphine (1.78–17.8 mg/kg) and spiradoline (1–10 mg/kg) dose‐dependently increased the latency for rats to remove their tails from water maintained at 50°C. MCAM (1–10 mg/kg) attenuated the antinociceptive effects of morphine in a dose‐ and time‐dependent manner, with 10 mg/kg MCAM producing a 30‐fold rightward shift in the morphine dose‐effect curve 1 day after it was administered. For at least 37 days after administration of the largest dose of MCAM, doses of 178–560 mg/kg of morphine were needed to produce a maximal antinociceptive effect. In contrast, the spiradoline dose‐effect curve was not changed 1 day after administration of 10 mg/kg MCAM, although in the same rats the antinociceptive effects of morphine were attenuated 4 days later (i.e. 5 days after MCAM administration). Thus, MCAM produces a sustained and selective antagonism of the antinociceptive effects of mu opioid receptor agonists. Under these conditions, antagonism by MCAM was surmounted by very large doses of morphine, although it remains to be determined whether the antinociceptive effects of those doses of morphine are mediated by mu opioid receptors. Nevertheless, the selectivity of MCAM in antagonizing the effects of mu opioid receptor agonists suggests that pain could be treated through mechanisms other than mu opioid receptors in patients that are taking MCAM for opioid abuse or overdose.

Support or Funding Information

Supported by NIH (R01DA005018; R01DA07315) and the Welch Foundation (AQ‐0039).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Manganese exposure augments misfolded α‐synuclein‐induced proinflammatory M1 microglial phenotype and inflammasome activation
Authors: Kondru Naveen , Manne Sireesha , Hepker Monica , Malovic Emir , Jin Huajun , Anantram Vellareddy , Kanthasamy Arthi , Kanthasamy Anumantha G
Published: June 2021

Sustained microglial activation is a key player in the immunopathogenesis of several neurodegenerative disorders including Parkinson's disease (PD). Chronic exposure to the environmental toxicant manganese (Mn) has been implicated as a risk factor for PD. We have previously demonstrated that misfolded and aggregated human α‐synuclein (αSynPFF) induces microglial activation. Recently, we have shown that chronic Mn exposure induces neuroinflammation by impairing mitochondrial dynamics. In this study, we determined whether Mn exposure alters the specific RNA transcripts in response to the αSynPFF proteostatic challenge. We systematically characterized the transcriptome of mouse microglia in response to Mn and/or αSynPFF using RNA sequencing. Treating a mouse microglial cell model with αSynPFF significantly induced both cytokine and interferon‐g signaling pathways. In contrast, Mn treatment caused distinct changes to pathways related to cellular senescence and apoptosis. Intriguingly, co‐treatment with Mn and αSynPFF caused profound enrichment of transcripts, including IL‐6, IL‐12b, IFN‐β, IL‐1α, and IL‐1β CXCL2, CXCL3, CXCL10, CCL5‐R, and Nos2, that signify the proinflammatory M1 microglial phenotype. These targets were further validated by real‐time qRT‐PCR, immunoblotting, and immunocytochemistry. As anticipated, cotreatment with Mn and αSynPFF lead to significant upregulation of the mRNA expression of IL‐6, Nos2, IL‐1α, and IL‐1β in a synergistic manner when compared to either treatment alone. Additionally, Mn and αSynPFF co‐treatment elicited NLRP3 inflammasome activation when compared to either treatment alone or untreated control cells. Taken together, these findings identify that environmental toxicants, such as Mn, perturb microglial homeostasis, thereby leading to transformation to a pro‐inflammatory M1 microglial phenotypic state. Importantly, our study suggests that the environmental toxicant Mn can augment αSynPFF‐induced neuroinflammatory processes in microglia to accelerate neurodegeneration.

Support or Funding Information

NIH grants ES026892, NS088206, and W. Eugene Linda Lloyd Endowed Chair

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
This hyperoxia mouse model using the wavelet transform analysis of flowmotion signals helps to look further into microvascular dysfunction
Authors: Rodrigues Luis Monteiro , Silva Henrique , Ferreira Hugo , Gadeau Alain‐Pierre
Published: June 2021

The use of animal models still presents many difficulties mostly because (a) no single model accurately recreates one disease, (b) the use of so many models impair comparison of results and (c) extrapolation to human is very limited. We have been dedicated to develop the potential use of oxygen as a challenger to study microcirculatory function and regulatory mechanisms. In the present study we show how this hyperoxia mouse model helps to identify different events associated to angiogenesis, following an hindlimb ischemia procedure, and test its discriminative capacities in detecting relevant differences in microvascular function between healthy and non‐healthy mice. Animals (n=66) were divided in three groups ‐ Control (C) with 33 C57/BL6 non‐transgenic male mice, part of which (9) submitted to a hindlimb ischemia (HLI) procedure, a genetically modified diabetic group (DB) including 8 transgenic C57BLKsJ‐db/db obese diabetic mice and the corresponding internal control of 8 age‐matched C57BLKsJ‐db/+ mice, and a transgenic cardiac hypertrophy group (CH) with 9 BALB/c mice prone to develop cardiac failure and 8corresponding age‐matched internal controls. Animals were anesthetized with a ketamine ‐ xylazine mixture and perfusion data collect by Laser Doppler Flowmetry during baseline rest (Phase 1), while breathing a 100% oxygen atmosphere (Phase2) and during recovery (Phase 3) and compared. Laser Doppler (LD) imaging and flowmetry were used as assessment instruments allowing to follow up all the processes regarding the HLI recovery. The wavelet transform (WT) component's analysis was allowed to further distinct between groups. Hyperoxia by itself revealled that new vessels are not functionally equivalent to those in the non‐operated limb but that recovery, also involves this limb, suggesting a cooperation mechanism probably centrally mediated. The WT analysis suggests that cardiorespiratory, myogenic and endothelial components act as main markers. In DB group db/+ animals behave as the Control group, as expected, but WT analysis shown significant differences for myogenic and the endothelial components. Noteworthy was the increase of the sympathetic components in the db/db set, as in the NHE1‐OE animals, in both cases reported as a main component of these pathophysiological processes. In conclusion, this hyperoxia‐mouse model, including the WT component analysis of LDF signal, seems to be reproducible, robust and discriminative, providing a deeper look into these different expressions of microcirculatoru pathophysiology in different experimental conditions

Support or Funding Information

This work was supported by national funds from FCT I.P, within the project UID/DTP/04567/2016.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Limitations of Pulse Transit Time to Estimate Blood Pressure
Authors: Sklarsky Amanda , Garvin Nathan M , Pawelczyk James A
Published: June 2021

INTRODUCTION

Pulse transit time (PTT) is inversely related to blood pressure. Because PTT can be measured non‐invasively and with relative ease, it has received attention as a method to estimate blood pressure in mobile health applications. However, both vessel diameter and distensibility affect pulse wave velocity and PTT independent of blood pressure. In question is the utility of a simplified form of the Moens‐Korteweg equation when these factors are ignored.

OBJECTIVE

We tested whether or not PTT alone would be sufficient to overcome between‐subject and within‐subject variation in vascular tone to derive estimations of blood pressure that are sufficiently accurate for health monitoring.

METHODS

Both systolic BP (Finapres) and PTT (time between the R‐wave of the ECG and SBP peak) were determined in 17 healthy, college age men and women during three conditions that elicit large changes in sympathetic activity and blood pressure: static handgrip exercise (3 min at 30% maximum voluntary contraction), 2 min of post‐exercise circulatory arrest of the exercising limb, and cold nociception (3 min of hand immersion in an ice water slurry). HR, BP and PTT were recorded beat‐to‐beat and averaged in 30 second epochs. Regression analysis was used to relate SBP to PTT. Subject ID, autonomic test and the phase of testing (e.g., rest, intervention and recovery) were included as categorical predictors of BP to test the sensitivity of SBP estimation to individual variation, test specificity, and autonomic state, respectively.

RESULTS

Compared to resting conditions, SBP increased by an average of 47.1 ± 4.5 mmHg during SHG, 34.6 ± 4.4 mmHg during PECA, and 32.9 ± 4.1 mmHg during CPT (mean ± SE). The regression model accounted for 73% of the BP variance (P<0.0001); the SE of the intercept was 3.3% (8.5 mmHg). Autonomic state and intra‐individual variance accounted for more of the variance in the model than PTT and type of autonomic test.

CONCLUSION

Individual calibration reduces the error associated with PTT estimation of blood pressure. Changes in autonomic state can be sufficient to affect blood pressure estimations by more than 10 mmHg. This finding raises questions about simplifying the Moens‐Korteweg equation to estimate BP in mobile health applications, and suggests that autonomic state and its effect on vascular tone must be considered.

Support or Funding Information

Huck Institutes of the Life Sciences

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
A Potential Link between Glycine Metabolism, Glutathione and Diabetes
Authors: Jog Ruta , Chen Guohua , Wang Jian , Leff Todd
Published: June 2021

Type 2 diabetes (T2D) is accompanied by alterations in amino acid metabolism. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance and T2D identifying glycine as a biomarker of T2D and raising the possibility that altered glycine metabolism plays an active role in the etiology of the disease. The goals of our study are to determine if altered glycine metabolism plays a functional role in the development of diabetes. The glycine cleavage system (GCS) is the only biochemical route that degrades glycine in humans and loss‐of‐function mutations of GCS cause hyperglycinemia. Here, we show that the expression of the rate‐limiting enzyme of GCS, Glycine Decarboxylase (GLDC), is upregulated in livers of hyperinsulinemic mouse models of diabetes, and in hepatoma cell lines insulin stimulates transcription of the GLDC gene. We identified the insulin responsive transcription factor Sterol regulatory element binding protein 1c (SREBP‐1c) as the primary mediator of this insulin stimulatory effect. We also observed that altering GLDC expression levels strongly affected intracellular glutathione levels and levels of reactive oxygen species (ROS). Our findings suggest a working model in which Srebp1c‐mediated regulation of GLDC is responsible for the reduction of glycine levels seen in insulin resistant states and may play function as a compensatory mechanism to increase glutathione production as a defense against diabetes‐induced oxidative stress.

Support or Funding Information

This work is supported by NIH R21AG050741, and the Michigan Diabetes Research and Training Center.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Lactobacillus rhamnosus GG improves skeletal muscle fatigability in a mouse model of hyperhomocysteinemia
Authors: Majumder Avisek , Singh Mahavir , George Akash K , Homme Rubens P , Metreveli Naira , Tyagi Suresh C
Published: June 2021

Hyperhomocysteinemia (HHcy) can occur due to insufficiency in cystathionine‐β‐synthase (CBS), activity causing skeletal muscle fatigability however it is still unclear whether this effect is mediated via reduced intracellular calcium release or lower ATP production or both. Consumption of Lactobacillus rhamnosus GG (LGG) as a probiotic supplementation has been shown to improve overall exercise performance and the physical strength. Based on this understanding, we hypothesized that LGG administration might improve the muscle functions in a mouse model of HHcy via improving the calcium release from the sarcoplasmic reticulum (SR) compartment and thus inducing the ATP production in the muscle tissue. To study this we used 4 experimental groups of mice as follows: Group‐I: WT mice (C57BL/6J); Group‐II: genetically heterozygous CBS deficient mice (CBS+/−) + High Methionine Diet (HMD), Group‐III: CBS+/− + HMD + LGG (orally @ 2.5x105 CFU/d for 12 weeks), and Group‐IV: WT + LGG. Data revealed that CBS mice had significantly high tHcy levels, and lower body weight in comparison to the age‐matched WT mice, unlike the LGG treated CBS+/− mice. Whole animal muscle fatigability measurements (by swim‐test performance and grip strength test) showed that HHcy induced muscle fatigability in CBS+/− mice compared to WT mice and it was noticed that LGG supplementation was able to improve this effect. Moreover, when we measured the excitation‐contraction coupling via muscle myobath experiment, we found that the soleus muscle of CBS mice produced lower contraction force and showed longer relaxation duration as compared to the WT mice, and these effects were also seemed to be mitigated via LGG consumption. Finally, we found reduced ATP production and calcium release were also improved in the CBS mice group by LGG supplementation. In conclusion, this work highlights the therapeutic potential of LGG towards reversing the harmful metabolic effects of HHcy mediated skeletal muscle dysfunction.

Support or Funding Information

NIH (HL‐74815, HL‐139047, AR071789)

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Patterns of Dental Morphology and Disparity in the Eocene Herbivore Lineage Esthonyx (Mammalia, Tillodontia)
Authors: Luongo Ricki A , Cozart Hannah K , Ahrens Heather E
Published: June 2021

The extinct clade Tillodontia includes numerous species representing relatively common, specialized herbivores of the Paleogene. The Eocene (56 – 33.8 mya) fossil record of the Bighorn Basin, Wyoming contains abundant fossils of the tillodont lineage, Esthonyx. Due to the abundance of specimens and their specialized diet, Esthonyx provides a valuable case study in phenotypic variation during climatic change over an extended temporal scale. Our objective was to quantify morphological disparity along the tooth row and assess variation between species and through time. To evaluate patterns of dental variation within Esthonyx, we used landmark‐based geometric morphometrics. Twelve landmarks representing prominent cusps and additional anatomical features in occlusal view of the lower fourth premolar and three molars were digitized for analysis. Principal components analysis indicated that the majority of shape variation, though very slight, occurred within the trigonid. Along the tooth row, p4 and m3 possessed greater disparity than m1 and m2; however, those differences were not significant. When dental loci were examined by both species and temporal unit, distinct species groupings and temporal shifts were difficult to distinguish because of the well‐conserved dental morphology within the lineage. In total, these results indicate that the lower dentition of Esthonyx is relatively conservative both along the tooth row, as well as between species and through time. The lack of evidence for morphologic change during significant climatic events may indicate low capacity for evolution and could have ultimately led to the extinction of this lineage.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The Influence of Gravitational Gradients on American Alligators (Alligator Mississippiensis)
Authors: Knoche Lucas , Young Bruce , Kondrashova Tatyana
Published: June 2021

Background

Cranial fluids of vertebrae mammals are composed of arterial blood, venous blood, and cerebrospinal fluid that can be altered by orthostatic pressures; head‐down postures can elevate intracranial pressure and carotid/jugular luminal area while head up postures produce opposite effects. Previous studies on aquatic and terrestrial snakes showed cardiovascular variation while arboreal snakes showed little cardiovascular variation during orthostatic transitions. Little experimental work regarding orthostatic transitions has been done on alligators. Alligators are known to have unique blood flow patterns due to active regulation of blood flow. The purpose of this study is to investigate the effects of gravitational tilt on vessel luminal diameter and ICP in alligators.

Methods

Live adult alligators (n = 5, 165 – 183 cm total length) were subjected to gravitational tilts between 45° head‐up to 45° head‐down in 15° increments. Short (30 s) and long (120 s) duration tilts were performed to assess barostatic reflex and ICP using ocular ultrasonography, respectively. Vascular ultrasonography was also used to assess luminal diameter of the carotid artery and jugular vein. Instantaneous heart rate was inferred from EKG recordings throughout tilts.

Results

Throughout orthostatic transitions, ocular ultrasonography revealed an increase in optic nerve sheath diameter (head down tilts) and a decrease in optic nerve sheath diameter (head up tilts). Head down tilts resulted in jugular and carotid dilation while head up tilts resulted in various jugular luminal diameters and minimal change in carotid diameter. Heart rate increased at the onset of all orthostatic transitions. There was no evidence for a barostatic response.

Conclusions

Ocular ultrasonography was used to non‐invasively assess intracranial pressure of reptiles. There was a linear relationship between orthostatic transitions and intracranial pressure due to redistribution of CSF. Compared to previous studies, orthostatic transitions produced similar results on vessel flow and diameter. Variations of vessel flow and diameter may be attributed to unusual patters of heart rate or blood shunts in the cephalic venous system. Increases in heart rate in all rotations may be due to a fear response. Additional studies are needed to further understand the underlying regulatory mechanisms that give rise to the alligator's heart rate and blood flow patterns.

Support or Funding Information

Funding: The Influence of Gravitational Gradients on American Alligators (Alligator Mississippiensis) project has been funded by A.T. Still University's Masters in Biomedical Sciences program.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
CRISPR/Cas9 Knockout‐Based Genome Wide Screening for Pathways Associated with Organochlorine Pesticide Toxicity in Human Dopaminergic Neurons
Authors: Russo Max , Sobh Amin , Tagmount Abderrahmane , Zhang Ping , Vulpe Christopher , Liu Bin
Published: June 2021

Environmental exposure to organochlorine pesticides (OCP) has been implicated as a risk factor for Parkinson's disease (PD), a devastating movement disorder characterized by massive loss of dopamine (DA) producing neurons in the substantia nigra and clinical symptoms including bradykinesia, rigidity and tremor. PD is the second most prevalent neurodegenerative disease and >95% of PD cases are usually not clinically diagnosed until after the age of sixty. OCPs are highly persistent in the environment and are extremely bio‐accumulative. Altered iron distribution in the brain and accumulation in the substania nigra is also observed in PD and may play a role in PD pathogenesis. To gain insight into the role of OCP exposure and iron dysregulation in PD pathogenesis, we carried out a genome wide (Brunello library, 19,114 genes, 76,411 sgRNA) CRISPR/Cas9 screen in SH‐SY5Y human dopaminergic neuronal cell line exposed to sub toxic doses of dieldrin or iron over one month to identify cellular components which modulate their toxicity. NGS sequencing of sensitive and resistant clones identified multiple genes, which when mutated significantly altered sensitivity to dieldrin or iron. Pathway analysis of the dieldrin data set implicated the protein degradation pathways previously implicated in inherited forms of PD centered on Parkin2 and SCNA. These results suggest a potentially common pathogenesis of idiopathic and inherited forms of PD. Additionally, the dieldrin results also suggested a potential role for the mTOR pathway, which is a signaling pathway that integrates both intracellular and extracellular signals and serves as a central regulator of cell metabolism, growth, proliferation and survival, is significantly involved in dieldrin associated toxicity. Fe toxicity on the other hand was shown to significantly alter dopamine receptor 2 (D2) signaling pathways. Together, these studies provide potentially novel insight into the dopaminergic toxicity associated with PD. Currently, we are conducting targeted validation of candidate genes identified in this study. Our work represents one of the first to apply genome wide CRISPR screens in a neuronal cell line and may reveal how an environmental toxicant and iron dysregulation in the brain contribute to PD. Additionally, this work may allow us to identify molecular mediators of neurodegeneration as potential therapeutic targets and/or diagnostic biomarkers.

Support or Funding Information

University of Florida Opportunity Fund.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Modulatory effects of fibronectin on calcium oxalate crystallization, growth, aggregation, adhesion on renal tubular cells, and invasion through extracellular matrix
Authors: Thongboonkerd Visith , Khamchun Supaporn
Published: June 2021

Fibronectin, an extracellular matrix (ECM) protein, has been thought to be involved in pathogenic mechanisms of kidney stone disease, especially calcium oxalate (CaOx) type. Nevertheless, its precise roles in modulation of CaOx crystal remained unclear. We thus performed a systematic evaluation of effects of fibronectin on CaOx monohydrate (COM) crystal (the major causative chemical crystal in kidney stone formation) in various stages of kidney stone pathogenesis, including crystallization, crystal growth, aggregation, adhesion onto renal tubular cells, and invasion through ECM in renal interstitium. The data showed that fibronectin significantly decreased crystallization, growth and adhesive capability of COM crystals in a dose‐dependent manner. In contrast, COM crystal aggregation and invasion through ECM migration chamber were significantly enhanced by fibronectin in a dose‐dependent fashion. Sequence analysis revealed two and six calcium‐binding and oxalate‐binding domains, respectively. Saturation of fibronectin with oxalate prior to crystal modulation assays could abolish all the effects of fibronectin, whereas saturation with calcium had minimal interference. These data strongly indicate the dual functions of fibronectin, which serves as an inhibitor for COM crystallization, crystal growth and adhesion onto renal tubular cells, but on the other hand, acts as a promoter for COM crystal aggregation and invasion through ECM. Moreover, its crystal modulatory activities are mainly due to oxalate‐binding capability.

Support or Funding Information

This study was supported by Mahidol University research grant and the Thailand Research Fund (IRN60W0004 and IRG5980006).

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Study the Effect of Irisin on Prostate Cancer Cells
Authors: Ko Fu‐Hsuan , Huang Feng‐Ting
Published: June 2021

According to the World Health Organization, prostate cancer is the second most common type of cancer and the fifth leading cause of cancer‐related death in men around the world. Epidemiological studies demonstrate that exercise can improve survival and reduce recurrence of prostate cancer. Studies indicate that humans' exercise serum has a growth inhibitory effect on prostate cancer cell proliferation, but which factor plays a major role is not clear. Recently, myokines secreted by skeletal muscle are believed to take part in cancer suppression. Irisin, an exercise‐induced myokine, promotes the “browning” of white adipocytes to brown‐like adipocytes. Several studies have demonstrated that irisin can inhibit cell progression in various cancer cells including those of breast cancer, lung cancer, and osteosarcoma. However, the underlying mechanisms of irisin's inhibitory effects on prostate cancer growth are not yet completely understood.

Our present study reveals that human recombinant irisin expressed in the E. coli system can inhibit cell migration and invasion of two prostate cancer cell lines, PC3 and 22Rv1. Irisin suppresses the proliferation of prostate cancer cells in a dose‐dependent manner, in addition to inducing cell cycle arrest and apoptosis in prostate cancer cells. These findings support the possibility of irisin treatment as a new therapeutic strategy against prostate cancer.

Support or Funding Information

This study was supported by the Department of Biochemical Science of Technology of National Taiwan University and the Taiwan Ministry of Science and Technology.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Ceranib‐2 inhibits HIF1‐α gene expression and induces apoptosis in HepG2 cells
Authors: ERKASAP NILUFER
Published: June 2021

The aim of this study to investigate the apoptotic effect of novel anti‐cancer drug ceranib‐2 in human liver carcinoma cells (HepG2). HepG2 cells plated at 1 × 105 cell/well in 24 well plates. Cell were treated with ceranib‐2 at 0,1, 1, 5, 10, 25 and 50 μM concentrations for 24 and 48 hours. Cell viability measured using 3‐(4,5‐d‐methylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide thyazolyl blue (MTT). HepG2 cell viability were decreased by 58 % after 24 and 48 hours ceranib‐2 treatment at concentration 10 μM. mRNA abundance of acid ceramidase (ASAH), caspase‐3, caspase‐8, HIF1‐α, and TNF‐ α conducted by Real time PCR (qRT‐PCR). Ceranib‐2 at 10 μM concentration increased mRNA abundance of caspase‐3 and no change were detected on caspase‐8 level vs control group (p<0.05) after 24 hours' treatment. No difference detected on caspase‐3 and caspase‐8 mRNA level after 48 hours' treatment with ceranib‐2 at 10 μM concentration. mRNA abundance of ASAH were reduced after 48 hours treatment with 10 μM ceranib‐2 (p<0.05). HIF1‐α expression was low after 24 hour compared to the control group (p<0,0001). TNF‐α mRNA were increase after 24 and 48 hours (p<0.05). Low abundance of ASAH in treated cells showed that 10 μM ceranib‐2 could inhibit ceramidase after 48 hour and this may trigger elavating ceramide concentration. We also observed that inhibition of ceramidase with ceranib‐2 inhibits HIF1‐α expression. Inhibition of HIF1‐a expression might induce apoptosis by reducing cell viability in HepG‐2 cells via ceranib‐2. In conclusion, ceranib‐2 may have anti‐cancer effect at 10 μM concentration in HepG2 cells. Finally, we have shown that inhibition of ASAH with ceranib‐2, induces apoptosis in HepG2 cells.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Sex Differences in the Stages of Cocaine Use Disorder and the Influence of the Mesolimbic Dopamine System
Authors: Mauterer Madelyn I , Jones Sara R
Published: June 2021

Traditional drug abuse research has primarily focused on male behavior and neurobiology; however, recent work in the field has revealed distinct differences between male and female cocaine responsivity. Specifically, females appear to be more vulnerable to the effects of cocaine, a phenomenon that has been shown to fluctuate with the reproductive cycle in both clinical and preclinical studies. For example, in human studies, women report greater subjective effects of cocaine during the follicular phase of the menstrual cycle, while in rodent studies, mice and rats exhibit greater cocaine taking behavior and preference during the estrus phase of the estrous cycle. Increased sensitivity to cocaine reward has been shown using many behavioral assays including those used to measure initiation of cocaine use, motivation for drug, extinction, and reinstatement. Increased cocaine taking behavior in females has been manipulated further to study the effects of social interaction, natural reward, exercise, and stress on intravenous cocaine self‐administration. Altogether, sex differences, both between males and females and across the stages of estrous, appear to be mediated by differences in the mesolimbic dopamine system according to recent work implicating dopamine projections from the ventral tegmental area to the nucleus accumbens core (NAc).

Here, intravenous cocaine self‐administration is used to assess drug taking behavior during the stages of drug addiction including initiation of use (acquisition), escalation, motivation, extinction, and reinstatement. Females in estrus showed faster times to acquisition of cocaine self‐administration and greater motivation to self‐administer cocaine using the behavioral economics protocol Threshold. Female cocaine abuse vulnerability further appears to be mediated by underlying neurobiological differences in cocaine taking between sexes and estrous stage. Females in estrus exhibit less synaptogyrin 3 expression in the NAc compared to their non‐estrus counterparts, a significant finding as decreased synaptogyrin expression in the NAc is associated with higher breakpoints in progressive ratio in males and is associated with dopamine transporter function. Furthermore, using ex vivo fast scan cyclic voltammetry (FSCV) in the NAc, females also exhibit greater dopamine transporter sensitivity to cocaine than males. Overall, these results add to the growing body of literature suggesting that females exhibit greater vulnerability to cocaine use and abuse across the stages of addiction and that these effects are due to an inherent neurobiological difference that this linked to the reproductive cycle and the mesolimbic dopamine system.

Support or Funding Information

T32AA007565, P50DA006634

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.