bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is The Cardiac Baroreflex Gain Altered in Spontaneously Hypertensive Rats?
Authors: Bonagamba Leni G.H. , Amorim Mateus R. , Moraes Davi J.A. , Machado Benedito H. 
Published: November 2023

There is evidence that a reduction in the baroreflex gain contributes to the high blood pressure in SHR. In the present study performed in conscious freely moving rats, we hypothesized that the baroreflex gain was not altered in SHR. To address this question we used two methods for evaluation of the cardiac baroreflex: a) the sequence analysis technique, and 2) the peak of changes in heart rate in response to increase (phenylephrine, PHE) and decrease (sodium nitroprusside, SNP) in mean arterial pressure (MAP) of Wistar (n=15) and SHR (n=21). The sequence analyses were used to evaluate the cardiac baroreflex function over the natural range of variation of arterial pressure, without any pharmacological tools. Considering that the sequence analyses are restricted to a narrow range of arterial pressure variability, we also evaluated the maximal bradycardic response (peak) to pressor response to PHE (i.v.) as well the maximal tachycardic response (peak) to fall in pressure in response to SNP (i.v). All experimental protocols were performed in conscious freely moving rats, previously anesthetized for catheterization of the femoral artery (arterial pressure recordings) and vein (i.v. injections), which were approved by the institutional ethical committee (#187/2011). The peak of reflex bradycardia in SHR in response to PHE was evaluated during the normalization of the MAP by continuous infusion of SNP (from 140 ± 2 to 101 ± 1 mmHg). The data from the sequence analyses show that the slopes of these sequences in both groups were similar (1.89 ± 0.2 vs 2.03 ± 0.2 ms mmHg−1), while the data from changes in MAP in response to PHE (49 ± 4 vs 39 ± 2 mmHg) show that the peak of bradycardic response in SHR was similar to Wistar (−107 ± 13 vs −91 ± 5 bpm). With respect to the reflex tachycardia to fall in MAP in response to SNP (−39 ± 3 vs −51 ± 12 mmHg) it was observed that the peak of tachycardia in SHR was also similar to Wistar (+107 ± 7 vs +112 ± 15 bpm). The data of this study, using two different experimental approaches, are showing that the gain of the cardiac baroreflex in SHR is not altered when compared to Wistar rats. We conclude that changes in the autonomic cardiac components of the baroreflex are not contributing to the high level of MAP observed in SHR.Support or Funding InformationFAPESP and CNPq
Obstructive Apnea Induces Similar Sympathetic Activation Across Several End Organs Independently of Chemoreceptors Afferents
Authors: Ferreira Caroline B , Schoorlemmer Gus H. , Cravo Sergio L , Stocker Sean D 
Published: November 2023

Obstructive sleep apnea increases muscle sympathetic nerve activity (SNA) in humans that contributes to cardiovascular dysfunction including hypertension. Several studies suggested that hypoxia is the main mechanism involved in the sympathoexcitation. The purpose of the present study was to determine whether there are regional difference in apnea‐induced sympathetic activation and asses the contribution of carotid chemoreceptors in cardiorespiratory and sympathetic responses induced by apnea. Male Sprague‐Dawley rats (270–350 g) were anesthetized with urethane (1.2 g/kg IV) and prepared for simultaneous recording of renal, splanchnic, and lumbar SNA, phrenic nerve activity (PNA) and arterial blood pressure (ABP). Apneas were performed by clamping a tracheal tube over 20 s while rats were spontaneously breathing room air and repeated in 100%O2. Apneas in room air produced similar increases in SNA across several nerves (Δ lumbar: 117±14%; Δ renal: 114±17% and Δ splanchnic: 124±12), hypertension (Δ: 12±2 mmHg), and increased PNA amplitude (Δ: 755±121%) whereas decreased of PNA frequency (Δ: −70±5 burst/m). Hyperoxia reduced the sympathetic activation (Δ lumbar: 56±6%; Δ renal: 40±4%, Δ splanchnic: 47±9%), pressor response (Δ: 6±1) and PNA amplitude (Δ: 570 ± 94%) induced by apnea. In a separate group of rats, to test the contribution of the peripheral chemoreceptor afferents, carotid bodies were bilaterally inactivated. Cardiorespiratory and sympathetic responses by NaCN (0.04%) were abolished but not apnea‐induced responses. Pre‐treatment with ganglionic blockade (chlorisondamine, 5 mg/kg IV) abolished apnea‐induced hypertension (Δ: 2±1mmHg). A last series of experiments were design to assess the effect of neuronal activity blockade and the role of glutamate receptor into NTS. Muscimol or AP5+CNQX cocktail reduced pressor and respiratory responses with no change in sympathetic activation evoked by apnea. Otherwise, importantly reduced cardiorespiratory and sympathetic responses induced by NaCN. Collectively, these findings suggest that other mechanisms rather than hypoxia might contribute for increase in sympathetic outflow induced by obstructive apnea.Support or Funding InformationCoordination for the Improvement of Higher Education Personnel (CAPES) and NHLBI R01 HL‐113270, American Heart Association Established Investigator Grant
Utilizing ATP‐Dependent Chromatin‐Remodeling Complexes to Study Vascular Biology
Authors: Crosswhite Patrick 
Published: November 2023

In eukaryotic cells, ATP‐dependent chromatin‐remodeling complexes aid in the regulation of gene replication, transcription, and DNA repair because nuclear factors necessary for achieving these tasks cannot access DNA when it is tightly bound to histones. Recent investigations have revealed that the switching/sucrose nonfermenting (SWI/SNF) and chromodomain helicase DNA‐binding (CHD) group of complexes are critical for embryonic vascular development. Our understanding of chromatin‐remodeling complexes in postnatal blood vessels however, remains inadequate. This study aims to characterize the expression of the SWI/SNF and CHD complexes in two models that alter vascular homeostasis: a hypertensive and aging model. In the aging model, transcripts of the SWI/SNF complex containing Brahma were aberrantly expressed in kidney samples, an organ vital to maintaining proper fluid balance and blood volume. Due to their ability to impact gene transcription in vascular cells (endothelial and smooth muscle), chromatin‐remodeling complexes are ideal molecular tools to aid in the identification of novel genes and signaling pathways involved in pathological changes in blood vessels. These initial findings emphasize the need to further investigate mechanistically how chromatin‐remodeling complexes can regulate vascular homeostasis.Support or Funding InformationAHA POST#21180005
A Micropuncture Study of the Net K Secretion in Thick Ascending Limb of Mice on a Low Na High K Diet
Authors: Wang Bangchen , Wen Donghai , Yuan Yang , Cornelius Ryan J , Li Huaqing , Wang‐France Jun , Sansom Steven C 
Published: November 2023

Understanding the effect of a cardio‐ and reno‐protective low Na high K diet (LNaHK) on renal K handling is crucial to choosing diuretics and anti‐hypertensives for patients on such diets. We previously showed that furosemide, an inhibitor of the Na‐K‐Cl cotransporter (NKCC2) in the thick ascending limb (TAL), increased urinary K excretion (UKV) in mice on a control diet but decreased UKV in mice on LNaHK. We hypothesized that there is a net K secretion in the TAL of mice on LNaHK. Male C57BL/6 mice were given either a control diet or LNaHK for 7–14 days. Mice were anesthetized and received modified saline (140mM NaCl, 5mM KHCO3, 2% mannitol) intravenously. Free‐flow micropuncture was performed using K‐selective micro‐electrodes to measure the K concentration in the early distal tubule (EDT) before and after intravenous administration of vehicle (60μL 0.9% NaCl) or furosemide (60μL, 2mg/mL). Urine was collected via a bladder catheter. Urine Na concentration was measured by a flame photometer. Within 10 minutes of administration, furosemide increased [K] in the EDT of mice on a control diet (Δ = 1.88 ± 0.45 mM; N = 3) but decreased that of mice on LNaHK (Δ = −3.52 ± 0.85 mM; N = 4). Vehicle did not affect [K] in the EDT of mice on either diet. The increase in urinary Na excretion after furosemide was much greater in mice on LNaHK (1298 ± 354; N = 5 vs. 240 ± 56 nmol/min; N = 3). These results indicate that there is a net K secretion in TAL of mice on LNaHK, and it is associated with increased NKCC2 activity.Support or Funding InformationThis project was supported by NIDDK: F30 DK108456, RO1 DK092474.
Molecular Diversity of Pulmonary Sensory Neurons Revealed by Single Cell RNA Sequencing
Authors: Liu Yin , Krasnow Mark A 
Published: November 2023

Pulmonary sensory neurons are primary sensory neurons that monitor lung physiological state, and communicate that information to the central nervous system. Many symptoms associated with pulmonary diseases, such as chronic cough, dyspnea (breathlessness), and airway hyperresponsiveness, are presumed to result from abnormal behaviors of these neurons. Past studies indicate that pulmonary sensory neurons are heterogeneous in their morphologies, functions and molecular identities. However, a complete understanding of their molecular and functional diversity is still lacking. Here, we perform single cell RNA sequencing (scRNA‐seq) on mouse pulmonary sensory neurons to elucidate the genome‐wide expression profile of over a hundred individual pulmonary sensory neurons. Through unbiased clustering analysis of the expression data of these neurons, we define 7 major classes of pulmonary sensory neurons. Each class expresses distinct sets of genes implicated in physiological sensing, which predict the specific sensory functions of each class. The gene expression profiles also identify specific molecular markers for each class, which we are using to elucidate their structures, map their terminal locations and receptive fields in the lung, measure their activity, identify their synaptic partners, and reveal the physiological consequences of their activation.Support or Funding InformationDamon Runyon Postdoctoral Research Fellowship (Y.L.)M.A.K. is an investigator of the Howard Hughes Medical Institute
Investigation of the effects of titanium dioxide and cerium oxide nanoparticles on liposomes using fluorescent dye leakage
Authors: Foster Brandon , Larios Mitchell , Smith Virginia 
Published: November 2023

Nanoparticles are common additives in many consumer products and medicines, including foods, toothpaste, and other personal care items. Despite their ubiquity, there has been limited research into the disruptive effect of nanoparticles on biological membranes. Using synthetic liposomes as model membranes, we used fluorescent dye leakage to analyze the effects of two types of nanoparticles: titanium dioxide nanoparticles, which are used to whiten and brighten products, and cerium nanoparticles, which have shown promise as biological anti‐oxidants. Liposomes were formed from different types of purified lipids using the extrusion method. The pH‐dependent dye fluorescein was trapped inside the liposomes, which was maintained at pH 10 by a glycine buffer, while the buffer outside the liposomes was maintained at a neutral pH where the dye would be quenched. By monitoring the fluorescence emission intensity of the liposome solution as nanoparticles were added, it was possible to determine rates of leakage as a function of NP concentration, solution temperature, and NP diameter. Controls were performed in the absence of nanoparticles and in the presence of known membrane disruptors such as detergents. In conclusion, we have developed an assay to investigate the disruption of lipid bilayers by nanoparticles. Preliminary results from the assay indicate that low micromolar concentrations of nanoparticles increase the rate of dye leakage from the liposomes by more than a factor of two, consistent with particle interaction and membrane disruption. These results will be presented in the context of a larger, ongoing study that investigates mutagenicity and cytoxicity of nanoparticles.Support or Funding InformationDefense Threat Research Agency
Making Science PhUn: Build, Design, and Connect
Authors: Silveyra Patricia , Chiota Lauren , Nagarajan Padmanabhan 
Published: November 2023

To celebrate PhUn week, Milton Hershey School high school students in Anatomy and Physiology classes hosted Dr. Patricia Silveyra, a lung physiologist, APS member, and Assistant Professor at the Penn State College of Medicine. The visit objectives included discussion about lung physiology, diseases of the lung, and what diagnostic tools doctors use to assess lung function and diseases such as COPD and asthma.The visit also included a hands‐on activity that required students to build, design, and test a homemade spirometer; a diagnostic tool doctors use to measure lung function. Students used various materials such as plastic 2‐liter and 4‐liter bottles and plastic tubing to design and build their spirometer. Once the spirometer was prepared students were able to test their design. Students measured and recorded their vital capacity (VC), total lung capacity (TLC), residual volume (RV), and expiratory reserve volume (ERV). Future lessons on lung function and physiology required students to revisit their measurements to graph and analyze their values. Identifying differences between values observed for normal lung function and those measurements observed in patients with lung diseases will be a cumulative activity.Students appreciated the opportunity to learn from a professional in the medical field. Dr. Silveyra was able to connect with the students very easily and relate the activity to the student's lives. The students benefited from the application and authenticity of the build, design, and test spirometer model activity.
Monitoring the Effect of Diet and Dietary Supplements on Lipid Accumulation in Drosophila melanogaster Larvae: An Opportunity to Provide a Course‐Based Undergraduate Research Experience
Authors: Daggett Melissa A. F. , Torres Alejandra Nunez , McFarlin Shane , Goodroad Samual L. 
Published: November 2023

Drosophila is an emerging model organism in which to study the effects of diet on the regulation of metabolism and physiological function. In order to analyze the effect different diets and food additives have on the accumulation of lipids in Drosophila larvae, we have used a carbohydrate rich and optimized high protein diet to expand on an established method to monitor the accumulation of lipids in third in star Drosophila larvae known as the floating larvae assay. We report on the simplicity and utility of using the floating larvae assay to access changes in lipid accumulation in flies raised on different diets and dietary supplements. Procedures for expanding the assay using common molecular, biochemical and cellular techniques in an upper level teaching laboratory, and in offering and delivering a course‐based undergraduate research experience is presented.Support or Funding InformationMissouri Western State University PORTAL (Program of Research Teaching and Applied Learning)
Unfolded protein response regulates yeast Arl1p activation at late‐Golgi via phosphorylation of Arf GEF Syt1p
Authors: Lee Fang‐Jen Scott , Hsu Jia‐Wei , Tang Pei‐Hua , Wang I‐Hao , Liu Chia‐Lun , Chen Wen‐Hui , Tsai Pei‐Chin , Chen Kuan‐Yu , Chen Kuan‐Jung , Yu Chia‐Jung 
Published: November 2023

ADP‐ribosylation factor (Arf) GTPases are key regulators of membrane traffic at the Golgi complex. In yeast, Arf guanine nucleotide‐exchange factor (GEF) Syt1p activates Arl1p, which was accompanied by accumulation of golgin Imh1p at late‐Golgi, but whether and how this function of Syt1p is regulated remains unclear. Here, we report that the Ire1p‐mediated unfolded protein response (UPR) modulated Arl1p activation at the late‐Golgi. Arl1p activation was dependent on both kinase and endo‐RNase activities of Ire1p. Moreover, constitutively active Hac1p restored the Golgi localization of Arl1p and Imh1p in IRE1‐deleted cells. Elucidating the mechanism of Ire1p‐Hac1p axis actions, we found that it regulated phosphorylation of Syt1p, which enhances Arl1p activation, recruitment of Imh1p to the Golgi, and Syt1p interaction with Arl1p. Consistent with these findings, the induction of UPR by tunicamycin treatment increases phosphorylation of Syt1p, resulting in Arl1p activation. Thus, these findings clarify how the UPR influences the roles of Syt1p, Arl1p, and Imh1p in Golgi transport.Support or Funding InformationNational Science Council of Taiwan (NSC‐104‐2320‐B‐002‐048‐MY3)
Chlorinated Lipids Induce Increased Cortical Stiffness in Microvascular Endothelial Cells
Authors: Birkhead Travis Michael , Kalogeris Theodore , Yu Hong , Meininger Gerald , Ford David , Ronald Korthuis 
Published: November 2023

Elastic properties of the vascular endothelium are critical to its role in controlling blood flow, pressure, vascular tone, adhesion of platelets and leukocytes, permeability and other homeostatic functions. Dysregulation of these endothelial functions are hallmarks of the inflammation produced in response to ischemia‐reperfusion, but it is not clear to what extent altered endothelial elasticity plays a role in the endothelial response to specific pro‐inflammatory stimuli. Cellular and plasma lipids that have been chlorinated by reacting with hypochlorous acid (HOCl) produced by neutrophil myeloperoxidase (MPO) have been shown to increase several markers of endothelial inflammatory activation. However, their effect on endothelial elasticity is unknown. We have begun to explore this issue in cultured endothelial cells. Human microvascular endothelial cells (HMEC‐1) were cultured to varying levels of confluence, incubated with 10 μM of 2‐chlorohexadecanoic acid (Cl‐HA), hexadecanoic acid (HA), 2‐chlorohexadecanal (Cl‐HDA), or hexadecanal (HDA), or 10 ng/ml TNF‐α, and cortical stiffness was measured using atomic force microscopy (AFM). Treatment with chlorinated lipids showed confluence‐dependent increases in stiffness, while non‐chlorinated lipids tended to decrease stiffness when compared with EtOH diluent. While the effect of chlorinated lipid varied with confluence, TNF‐α (positive control) produced consistent results independent of culture confluence. These results show for the first time, that the chlorinated lipids known to be produced through reaction with neutrophil MPO‐derived HOCl, increase cortical stiffness in microvascular endothelial cells.Support or Funding InformationRO1‐GM115553 & R01‐AA221081
The role of calcium sulfide in intrinsic and extrinsic apoptotic pathways in non‐small lung cell adenocarcinoma
Authors: Rosado Maria Milagros Figueroa , Forti Kevin Muñoz , Torres Bryan , Bernard Faviola , Arroyo Gerardo , Ruiz Abigail , Santiago Pedro , Perez Jaileene , Gonzalez Jonathan , Castro Miguel , Suarez Edu 
Published: November 2023

Apoptosis is the process of programed cell death and it is characterized by metabolic changes and energy‐dependent mechanisms. It occurs normally in the development and regeneration of tissues, to insure proper functionality of systems, and it can also function as part of the cellular response against disease or cytotoxicagents. Still, a variety of internal and external stimuli trigger apoptotic cascades, which are categorized in two signaling pathways, extrinsic and intrinsic; they are based on the origin of the stimuli, and the mediators involved. Previous studies in our laboratory, showed that non‐small lung cell adenocarcinoma cell line (ATCC HCC827) treated with proprietary calcium sulfidenanoclusters (CaS) [3.8μM] showed increased apoptotic activity following 48 hours that become statistically significant at 72 hours (p<0.05) without affecting non‐cancerous cell lines (MCR5) after 24‐hours. The objective of this study was to determine the expression of intrinsic (Bcl‐2 and caspase‐3) and extrinsic (caspase‐8 and Bax) apoptotic factors in HCC827 cells upon addition of a single dose of CaS nanoclusters evaluated at 24 hours intervals up to 72‐hours. We hypothesized that CaS nanoclusters will increase the intrinsic and extrinsic apoptotic signaling pathways. DMSO [1%] was used as a negative control and Etoposide[10μM] as a positive control. The flasks were randomly assigned to one of the treatments in triplicates. We used Western Blot, densitometry, and statistical analyses to evaluate changes in expression of the studied proteins. The preliminary data showed that: (1) at 72 hours, the expression of the pro‐apoptotic Bax increased and the anti‐apoptotic Bcl‐2 decreased; (2) at 24 and 48 hours the expression of full caspase‐8 and their respective cleaved variations increased, as well as the pro‐apoptotic caspase‐3 when HCC827 cells were treated with CaS nanoclusters (p<0.05). These results suggest that CaS nanoclusters have apro‐apoptotic effect, involving both intrinsic and extrinsic pathways during the specified timelines. We are currently studying additional pro apoptotic mediators in the intrinsic (caspase‐9, ‐12) and extrinsic (caspase‐7) to elucidate the level of effect of CaS nanoclusters in these pathways.Support or Funding InformationThis work was supported by: UPRPRISE Program NIH Grant #R25GM096955
TRPC1‐STIM1 Activation Modulates Transforming Growth Factor β‐induced Epithelial‐to‐Mesenchymal Transition
Authors: Schaar Anne , Sukumaran Pramod , Sun Yuyang , Dhasarathy Archana , Singh Brij 
Published: November 2023

ObjectiveTumor metastasis is the principal cause of cancer‐associated deaths; therefore, identifying the mechanism(s) of Epithelial‐to‐Mesenchymal Transition (EMT) mediated metastasis, including the role of the ubiquitous second messenger Ca2+, is important to limit cancer induced death.Activation of Epithelial‐to‐Mesenchymal Transition (EMT) is important for tumor metastasis to occur. Although growth factors such as TGFβ and EGF have been shown to induce EMT in breast epithelial cells, the mechanism resulting in migration is not well understood. TGFβ induced EMT down regulates the epithelial factors E‐cadherin and increases expression of mesenchymal neural cadherin (N‐cadherin) through a process known as the ‘cadherin switch’. Cleavage of E‐cadherin in both localized and metastatic tumors is believed to be mediated by the calcium (Ca2+)‐dependent calpain family of cysteine proteases, however the ion channel and the source of Ca2+ entry is not yet identified. Changes in intracellular Ca2+ are the result of either the release of Ca2+ stores from the endoplasmic reticulum (ER) that initiates store‐operated Ca2+ entry (SOCE) mechanism, or direct Ca2+ entry from the extracellular space upon membrane depolarization. During initiation of SOCE (when ER Ca2+ stores are depleted) Stromal Interaction Molecule 1 (STIM1) is shown to aggregate at the ER‐PM junctions, where it interacts with proteins such as the Transient Receptor Potential Canonical 1 (TRPC1) channel causing Ca2+ influx. Herein, we provide evidence that Ca2+ entry into the cell, especially upon store‐depletion, plays an important role in TGFβ‐induced EMT by promoting cellular migration and potentially leading to metastasis. The increased migration by TGFβ in non‐cancerous cells was due to the loss of E‐cadherin along with a subsequent increase in N‐cadherin levels. Importantly, TGFβ‐treatment increases store‐mediated Ca2+ entry, which was essential for the activation of calpain cleavage of E‐cadherin. Inhibition of Ca2+ entry by using non‐specific Ca2+ channel blocker SKF‐96365, significantly decreased Ca2+ entry, decreased TGFβ‐induced calpain activation, and suppressed the loss of E‐cadherin along with inhibiting cell migration. Furthermore, TRPC1 function as an endogenous Ca2+ entry channel and silencing of either TRPC1 or STIM1 significantly decreased TGFβ induced Ca2+ entry as well as inhibited TGFβ‐mediated calpain activation and cell migration. Together these results suggest that disrupting Ca2+ influx via TRPC1/STIM1 mechanism reduces calpain activity, which could restore intercellular junction proteins thereby inhibiting EMT induced motility.Support or Funding InformationFinancial support was received from the National Institutes of Health (DE017102) awarded to B.B.S. and 5P20GM104360 awarded to AD.