bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Role of AT1a Receptors in The Proximal Tubules of The Kidney in Renal Ischemia‐Reperfusion Injury in Mice
Authors: Zhang Jianfeng , Li Xiao C , Zhuo Jia L 
Published: November 2023

It is well recognized that the renin‐angiotensin system via angiotensin II (ANG II) plays an important role in the pathogenesis of renal ischemia‐reperfusion injury, but the mechanisms involved remain incompletely understood. The present study used global (Agtr1a−/−or AT1a‐KO) and conditional proximal tubule‐specific AT1a‐KO (PT‐AT1a‐KO) mouse models to test the hypothesis that deletion of AT1a receptors globally or selectively in the proximal tubules of the kidney attenuates renal ischemia‐reperfusion injury. Three groups (n=6–8/per group) of adult male C57BL/6J (WT), AT1a‐KO, and PT‐AT1a‐KO mice were subjected to sham surgery or bilateral kidney ischemia for 40 min, followed by reperfusion recovery for 7 days. Basal systolic blood pressure (SBP) was 25 ± 3 mmHg lower in AT1a‐KO mice (p<0.01) and 13 ± 3 mmHg lower in PT‐AT1a‐KO mice, respectively, than in WT mice (p<0.05). 7 days after renal ischemia‐reperfusion, there were no differences in SBP, 24 h urine and urinary sodium excretory responses in all strains, compared with their respective basal levels. However, kidney wt. to body wt. ratio was significantly increased in AT1a‐KO and PT‐AT1a‐KO mice (p<0.05). Renal ischemia‐reperfusion injury and recovery was assessed by Masson Trichrome staining and compared between WT, AT1a‐KO and PT‐AT1a‐KO mice. No significant glomerular, tubulointerstital, and peri‐vascular fibrotic responses were observed in sham controls of all strains. However, significant fibrotic responses were observed in the glomeruli, cortical tubulointerstitial and peri‐vascular tissues in WT mice 7 days after renal ischemia reperfusion injury (p<0.01). Unexpectedly, glomerular, tubulointerstital, and peri‐vascular fibrotic responses to renal ischemia reperfusion injury were significantly worsen, rather than attenuated, in global AT1a‐KO mice (p<0.01). By contrast, deletion of AT1a receptors selectively in the proximal tubules markedly attenuated glomerular, tubulointerstital, and peri‐vascular fibrotic responses in PT‐AT1a‐KO mice 7 days after renal ischemia‐reperfusion injury (p<0.01). These results indicate that AT1a receptors in the proximal tubules of the kidney play an important role in renal ischemia‐reperfusion injury, and that deletion or blockade of AT1a receptors in the proximal tubules may attenuate renal ischemia‐reperfusion injury.Support or Funding InformationThis work was supported in part by grants from NIDDK & NIGMS (2R01DK067299 & 1R01DK102429) to Dr. Zhuo.
Chronic amphetamine exposure causes long‐term effects on dopamine uptake
Authors: Ferdous Nafisa , McCowan Talus J , Carvelli Lucia 
Published: November 2023

The dopamine transporter (DAT) is a plasma membrane transporter that clears released dopamine from the synaptic cleft; therefore it is an important regulator of extracellular levels of dopamine. DAT is also the main molecular target of many drugs of abuse, most notably the psychostimulants cocaine and amphetamine. Amphetamine (AMPH) is a substrate of DAT and competes for reuptake with dopamine. Several groups have shown that acute AMPH treatments alter the function and the number of DAT on the cell membrane. However, no data is available regarding the long‐term effects of AMPH on DAT activity. Data collected in our laboratory suggest that parental AMPH exposure affects dopamine uptake in C. elegans dopaminergic neurons isolated from progeny. These results led us to hypothesize that reduced dopamine reuptake in subsequent generations, as a result of parental AMPH exposure, is caused by down‐regulation of DAT. In order to overcome the complexity of multicellular organisms and the challenges of primary cell isolation and culture, where very few cells differentiate into dopaminergic neurons, we investigated the long‐term effects caused by AMPH in simplified systems. Initial experiments were carried out in LLC‐PK1 cells, stably transfected with human DAT. Cells were pre‐exposed to AMPH for 15 hours and uptake assays, carried out after cells had doubled, showed a significant decrease in dopamine uptake compared to control (untreated cells). These data suggest that changes caused by AMPH were maintained after one cell cycle. We repeated the same experiment using the human neuroblastoma SH‐SY5Y cells which can be differentiated into authentic dopaminergic neurons. Prior to the uptake assay one group of undifferentiated SH‐SY5Y cells was exposed to AMPH for 15 hours and the other group was treated with control solution. The cells were then allowed to grow and cross generations before they were treated with Retinoic Acid (RA) to induce differentiation. Uptake assays carried out 5 days after RA initiated differentiation revealed a significant decrease in dopamine uptake in AMPH treated groups with respect to control. These results suggest that parental AMPH pretreatment down regulates the expression or activity of DAT. We are currently investigating whether chronic exposure to AMPH in progenitor cells alters DAT expression in daughter cells.Support or Funding InformationCOBRE P20 GM104360
Fumarate Regulates Hif1α, Superoxide, and Matrix in Zebrafish and Mouse Models of Diabetic Kidney Disease
Authors: You Young‐Hyun , Liu Chao , Huang Wei , Miller Yury I , Sharma Kumar 
Published: November 2023

We have recently found that fumarate, a TCA cycle metabolite, is increased in early type 1 diabetes and may play a key pathogenic role in enhancing matrix accumulation and stimulation of Hif1α, key features of diabetic kidney disease (DKD). Administration of a single IP injection of fumarate to non‐diabetic BL6 mice induced TGF‐β, SMAD3 and fibronectin in mice kidney cortex as compared with PBS‐injected control. Fumarate exposure to HEK293 cells led to an increase in HIF1α and TGF‐β expression, along with stimulation of collagen I, fibronectin, and α‐SMA. The role of fumarate was further explored in a zebrafish model of acute hyperglycemia. We found that 2% and 3% high glucose exposure for 24–48h decreased superoxide production in the pronephros of larval zebrafish, as measured by OX‐DHE fluorescence. A 2–3% glucose treatment also leads to a significant reduction in the expression of a zebrafish ortholog of the fumarate hydratase gene (fh) and protein. Exposure of zebrafish to 7.5–10 uM fumarate for 24h led to reduction of superoxide production and an increase in Hif1α and Collagen1a1a expression in zebrafish larvae. In conclusion, similar to what we previously observed in diabetic mice, fumarate enhances matrix stimulation and reduces superoxide production, possibly, via Hif1α activation in zebrafish. Taken together, our findings demonstrated that fumarate regulation has an important role in the development of DKD and may constitute a therapeutic target for the management of DKD.Support or Funding InformationThis work was supported by grants from NIH to K.S..
Females Have Altered Hemodynamics during Exercise Recovery with Caffeine Consumption
Authors: Grigoriadis Georgios , Bunsawat Kanokwan , Hilgenkamp Thessa Irena , Baynard Tracy 
Published: November 2023

BACKGROUNDCaffeine consumption alters blood pressure (BP) and heart rate (HR) via sympathetic stimulation and arterial stiffness, as well as smooth muscle contraction. HR and BP recovery from a stimulus, such as exercise, can provide insight into aspects of autonomic control. Sex differences have been reported for HR recovery (HRR) and BP recovery (BPR); however, it is unclear if sex differences in recovery would still exist under an exacerbated adrenergic condition (e.g. caffeine).PURPOSETo examine sex differences in BPR and HRR with caffeine consumption following maximal exercise.METHODSTen male (25 ± 3 yrs; 25.3 ± 3.5 kg/m2) and 8 female (26 ± 3 yrs; 22.8 + 2.4 kg/m2) individuals participated in a randomized, crossover study, with 400 mg of caffeine or placebo capsules ingested on 2 separate days. Each visit consisted of a maximal treadmill exercise. Beat‐to‐beat BP collected at rest, 5 and 15 min into passive recovery using finger photoplethysmography. HRR was recorded at the standard 1 and 2 min post‐exercise. Systolic (SAP), diastolic (DAP), mean (MAP), and pulse pressure (PP) change values from baseline rest to 5 and 15 min post‐exercise are reported in the table.RESULTSHRR, DAP, and MAP were not different between sexes for either placebo or caffeine. A sex x condition interaction (p<0.05) for the change in SAP and PP from baseline rest to 15 min was found. At 15 min post‐exercise, females had an increase in PP (p<0.001), whereas PP decreased in males.CONCLUSIONCaffeine consumption did yield sex differences in BPR, with females having higher SAP and PP during the recovery period from maximal exercise versus males. The difference in SAP and PP with caffeine may be due to delayed parasympathetic activity in females compared to males.

MALE
FEMALE

PLACEBO
CAFFEINE
PLACEBO
CAFFEINE

ΔHRR1min
26 ± 11
26 ± 11
28 ± 12
31 ± 14

ΔHRR2min
48 ± 14
47 ± 12
48 ± 18
47 ± 15

ΔSAP5min
5 ± 10
−6 ± 11
0.7 ± 8
3 ± 10

ΔSAP15min
5 ± 11
−6 ± 12
−1± 6
4 ± 10

ΔDAP5min
−2 ± 8
−9 ± 9
−5 ± 6
−5 ± 9

ΔDAP15min
−1 ± 8
−9 ± 9
−4 ± 4
−5 ± 7

ΔMAP5min
1 ± 8
−8 ± 9
−2± 7
−1± 11

ΔMAP15min
2 ± 9
−8 ± 9
−2 ± 5
−1 ± 9

ΔPP5min
6 ± 7
3 ± 7
6 ± 6
8 ± 6

ΔPP15min
7 ± 6
3 ± 8
3 ± 6
9 ± 5*

MEAN ± SD;
Significant different between placebo and caffeine (p<0.001)
“I Can Hear Heart Sounds Too, How About You?” Familiarizing First‐Graders to Heart Sounds With Homemade Stethoscopes and Encouraging Heart Healthy Eating Habits From an Early Age
Authors: Taylor Jessica C , Prior Barry , Porter Johnny 
Published: November 2023

PurposeThe purpose of this outreach was to familiarize elementary students with the concept of heart sounds heard through rudimentary homemade stethoscopes, heart rate detected by radial pulse, and to present healthy eating habits to support heart health during PhUn week 2015.MethodsThe team coordinated with the three first‐grade teachers at Sacred Heart Catholic School in Hattiesburg, MS. There were approximately 65 children that participated in the event. Paper towel cores were collected prior to PhUn week 2015 and delivered to the school approximately two weeks before the event date. Students were placed into pairs and given instructions for listening to heart sounds with a paper towel core “stethoscope.” One member of each pair, the “patient,” jumped up and down for 20 counts. Upon ceasing to jump the other member of the pair, the “physician,” placed the paper towel core stethoscope on the patient's chest and listened for the classic lub‐dub heart sounds. The students were then asked to switch roles and repeat the exercise. Medical student volunteers also demonstrated using two fingers to palpate the radial pulse and guided the students to find their own pulses. Finally, students were asked to place foods into two categories to demonstrate the role of nutrition in heart health. Pre‐selected foods were placed on one of two boards containing the titles, “Eat these foods more often” and “Eat these foods less often.”ResultsApproximately, one‐third of the students engaged during PhUn week 2015 had previously participated in this activity one or two times. Observational data suggests that previous exposure to this exercise predisposes the children to greater success in 1) hearing the heart sounds, 2) finding the radial pulse more easily than their classmates and 3) to answering physiology‐related questions, even with a one‐year absence in exposure to the outreach. Additional observational data suggests that sharing nutritional information helps students to consider wise food choices at an earlier age. Upon completion of the activity all of the children were aware that the heart beats constantly, that the heart makes sounds when it beats and that it is important to exercise and eat healthy foods for heart health. The children could also demonstrate the approximate size of their hearts by showing a clenched fist to classmates.ConclusionsPhUn week is and continues to be an important avenue for introducing young students to physiology and increasing their scientific knowledge base. Also, repeated outreach exposures may increase students’ retention of physiologic concepts despite separation of the events by more than 12 months.
Measuring Brain Wave Activity in High School Students through Biopac Science Lab
Authors: Pawlak Robert , Evans LeVisa , Andreasen Nicholas , Anthis Taylor , Gurovich Alvaro N 
Published: November 2023

The American Physiology Society (APS) has made it a goal to increase the understanding of physiology and promote careers in physiology. One of the APS initiatives that engages students is Physiology Understanding Week (PhUn). In this year's project, we used the Biopac MP40 system to measure brain function across high schoolers at South Vermillion High School in Clinton, IN. The activity was divided into 2 different days reaching 47 high schoolers taking two advanced anatomy and physiology classes. During the first day, 6 Biopac MP40 were available to both classes and 4 students per system collected data measuring brain function during 4 different conditions. The 4 conditions tested for brain function were 1) resting with eyes closed, 2) resting with eyes open, 3) sing a song in their head with eyes closed, and 4) read and solve a riddle. The second day, students analyzed the collected data and presented their main findings. The goal was to quantify the change in brain function when the difficulty of tasks is increased. While one student was tested other students gave commands and recorded data for alpha, beta, and delta waves. This data was then taken to construct charts so that the students could analyze the data for themselves. This activity helped the students apply their knowledge of neuro‐physiology to draw conclusion while expanding their knowledge of the brain. This interactive method enabled students to be more involved in their studies while taking an interesting new approach to physiology: a ‘PhUn’ approach.Support or Funding InformationSupported by IU AHEC 15/16 #PIU535 and APS PhUn week program
Teaching Reaction Time using Applied Technology in High School Students
Authors: Anthis Taylor N , Brown Carson , Cole Shelby N , Crecelius Arick , Pawlak Robert , Jarrett Steven , Miller Breena , Gurovich Alvaro N 
Published: November 2023

This project was designed to educate High School students on the importance of understanding neuro muscular physiology. Forty‐seven students from 2 upper anatomy/biology classes at South Vermillion High School in Clinton, IN learned how proprioception and nerve conduction velocity influence reaction time. The primary information was presented to the students in a PowerPoint and then demonstrated using an applied technology system (Biopac MP40). The Biopac MP40 is integrated with a laptop computer, and is used to show data by reading electrical impulses released by muscles. The Biopac MP40 synchronized two signals to determine a student's reaction time. It uses an acoustic signal, via headphones and the electrical signal sent by the electrodes placed on the student's arm to determine their reaction time. Twelve 4‐student small groups collected data from themselves. One student was the subject and the other three controlled the Biopac MP40 and wrote down the collected data. Finally, during a second day of this activity, students were asked to analyze and present the collected data, especially focusing on the difference between sex and arm dominance. This interactive method enabled students to be more involved in their studies while taking an interesting new approach to physiology: a ‘PhUn’ approach.Support or Funding InformationSupported by IU AHEC 15/16 #PIU535 and APS PhUn week program
7th Grade Students at Moanalua Middle School Have PhUn with Exercise Physiology
Authors: Ho Dao H. , Pierce Lisa M. , Washington Michael A. , Campbell Carmen E. , Murata Lee‐Ann M. , Hernandez Claudia A. , Criman Erik T. , Peebles Melina , Uyehara Catherine F.T. 
Published: November 2023

Researchscientists from the Department of Clinical Investigation at Tripler ArmyMedical Center (Honolulu, HI), brought PhUn to the classroom of Ms. MelinaPeebles at Moanalua Middle School (Honolulu, HI). Twenty‐eight 7th grade students spent the morning learning about science as a career choice, the importance of exercise in maintaining good health, and how cells, muscles, and the cardiovascular system all play a role in exercise physiology. The students participated in four activities, each relating to muscle physiology: 1)identifying different organelles of a cell and their functions, 2) learning about static and rhythmic exercise, 3) learning how exercise, such as dancing to music, affects heart rate, and 4) understanding how the cardiovascular system works to deliver oxygen to muscles. The pace and variety of the activities kept the students attentive, and excited about learning the “ins and outs” of exercise physiology. Some examples of how we made the activities engaging and educational for the students include: using a model of the heart and circulatory system to explain oxygen delivery to muscles, using stethoscopes and cell phone apps to measure heart rate, and using “shrinky dink” film to allow students to make their own key chain of a cell. Overall, PhUn day at Moanalua Middle School was a great success.Support or Funding InformationThe views expressed in this abstract are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.
A Day of Hands‐on Physiology Demonstrations Increases Understanding of and Excitement towards Physiology in a Native American Indian Population of Middle and High School Students
Authors: Becker Bryan K , Schiller Alicia M , Zucker Irving , Godfrey Maurice 
Published: November 2023

PurposeTo provide middle and high school students from Native American Indian reservations from Nebraska and South Dakota with interactive physiology activities to increase their understanding and familiarity with physiology and excitement toward science.MethodsAn activity‐based “Physiology Day” was held for approximately 300 middle and high school students from various Native American Indian reservations from Nebraska and South Dakota. Students rotated through 9 stations in small groups to complete hands‐on activities over diverse areas of physiology such as respiration, digestion, cardiovascular control, special senses, and more. Prior to completing any of the activities, students were given a questionnaire to determine their baseline familiarity with and attitudes toward physiology and science. Following the activities, the students were given a second questionnaire to gauge both the effectiveness of the various demonstrations and the students’ self‐perception of their understanding of basic physiological concepts and excitement toward science.ResultsAt the beginning of the day, 79% of students rightly identified Physiology as being the study of how the body works; however a large proportion of students (18%) identified physiology as the study of physics. Following the day of activities the proportion of students correctly defining physiology increased to 89%. When asked to evaluate the level of current understanding of physiology, only 1% of students identified as “knowing a lot” 64% identified as “knowing a little”, and over one third (35%) said they “know nothing” about physiology. Following the day of activities, students self‐evaluating that they “knew a lot” about physiology increased to 24%, “knowing a little” increased to 69% and “knowing nothing” dramatically decreased to 7%. All 9 of the activities ranked high in satisfaction and effectiveness with 82–94% of respondents saying they learned something or enjoyed the activity. We conclude that our hands‐on physiology demonstrations and activities are effective means by which to engage middle and high school students increasing both their knowledge and excitement toward physiology.Support or Funding InformationSEPA (RR032178) (OD011071)
Re‐evaluation of the effect of the phosphatase inhibitor okadaic acid on aquaporin 2 phosphorylation and trafficking
Authors: Day Jack , Ueberdiek Lars , Cheung Pui W , Bouley Richard , Brown Dennis 
Published: November 2023

Aquaporin‐2 (AQP2), the vasopressin (VP)‐sensitive water channel, plays an important role in water reabsorption. Accumulation of AQP2 on the plasma membrane in kidney collecting duct principal cells increases water permeability and is necessary for urine concentration. AQP2 trafficking is tightly regulated by phosphorylation and dephosphorylation, and the role of each of four phosphoserine residues (pS256, pS261, pS264 and pS269) has been intensively studied. Recent work in our laboratory has shown that erlotinib (Erl), an epidermal growth factor receptor (EGFR) inhibitor, induces AQP2 membrane accumulation in the absence of VP. Western blot analysis using selective phospho anti‐AQP2 antibodies showed a VP‐like effect. Here, we investigate how phosphatase inhibition affects trafficking and intracellular location of AQP2 in the presence of VP and erlotinib. We performed immunohistochemistry and western blotting on LLC‐PK1 cells stably expressing WT AQP2. Cells were treated with okadaic acid (OA, 1 μM), a phosphatase inhibitor specific for PP1 and PP2A, for 10 minutes before treatment with either VP (10 nM) or Erl (2 μM). Interestingly, OA treatment alone did not significantly increase AQP2 membrane accumulation in our cell model, in contrast to a previous report in CD 8 cells (Valenti et al 2000), but did modify its intracellular distribution into a perinuclear position. Despite the lack of AQP2 membrane accumulation, western blot analysis showed that OA alone increases phosphorylation at all four phosphorylation sites. The VP or Erl induced AQP2 membrane accumulation is not affected by OA, but unexpectedly, pretreatment with OA did not inhibit VP or Erl induced S261 dephosphorylation. This suggests that phosphoserines 256 and 269 are the main substrates of phosphatases inhibited by OA (i.e., PP1, PP2a) and that serine 261 is the substrate for an OA insensitive phosphatase activated by VP and Erl.Support or Funding InformationThe American Physiological Society supported this work