Reviewer Awards Research Articles

Best Reviewer Awards

Best Reviewer Awards

Outstanding Reviewer Award OR Spectrum 2023

Outstanding Reviewer Award OR Spectrum 2023

Advanced age and reduced hyaluronan synthesis impair glycocalyx integrity resulting in endothelial dysfunction

The glycocalyx (GC) is a densely structured, gel-like matrix that coats the inner lining of the vascular endothelium. The GC plays a pivotal role in regulating the integrity of the vascular endothelium, primarily through mechano-sensing and -transducing shear stress, while also preserving endothelial barrier function. With advancing age, the GC deteriorates concomitantly with its essential constituent, hyaluronan (HA), which may lead to endothelial dysfunction. Therefore, we hypothesized that advanced age and reduced HA synthesis alone or together will impair GC integrity resulting in endothelial dysfunction. We have generated a tamoxifen-inducible, endothelial cell-specific, knockout mouse model of a hyaluronan producing enzyme, hyaluronan synthase 2 (HAS2), in young (4-6 mo) and old (22-23 mo, n=9-12/group). HAS2 mRNA expression in carotid endothelial cell lysates were reduced by ~47% in endothelial cell HAS2 knockout (ecHAS2KO) vs wildtype (ecHAS2WT, p=0.004) after tamoxifen treatment. The perfused boundary region (PBR), indicative of GC barrier function, was evaluated in vivo in the mesenteric microcirculation. The PBR was significantly impaired with aging (young vs old ecHAS2WT, p=0.047) and genotype (young ecHAS2WT vs KO, p=0.012) but there was no additive effect of aging and genotype (old ecHAS2WT vs KO, p=0.989). Subsequently, GC thickness was determined by measuring the depth of GC collapsed by leukocyte passage through the mesenteric segments. GC thickness was diminished by ~53% with aging (young vs old ecHAS2WT, p<0.0001) and ~59% with genotype (young ecHAS2WT vs KO, p<0.0001) but there was no synergistic effect of aging and genotype (old ecHAS2WT vs KO, p=0.893). Mechano-sensing and -transducing properties of the GC were assessed using ex vivo flow-induced vasodilation in isolated carotid arteries with and without the intra-luminal infusion of HA degrading enzyme, hyaluronidase (HYAL). Flow-induced vasodilation was diminished with aging (young vs old ecHAS2WT, p<0.0001) but this age-related decline was dampened with HYAL (p=0.212). The vasodilatory response to flow was reduced with genotype (young ecHAS2WT vs KO, p<0.0001) but this effect was weakened with HYAL (p=0.953). There was no augmentative effect of aging and genotype with and without HYAL (all p≥0.883). Acetylcholine induced endothelium-dependent dilation (EDD), a measure of endothelial function, was examined ex vivo in isolated mesenteric arteries. The maximal EDD was diminished by ~23% with aging (young vs old ecHAS2WT, p=0.04) but not genotype (young ecHAS2WT vs KO, p=0.962). There was an additive reduction in maximal EDD by ~46% with aging and genotype (old ecHAS2KO vs WT, p=0.021). Endothelium-independent dilation in response to sodium nitroprusside, an exogenous nitric oxide donor, was not different across groups with either aging, genotype, or both (ALL p>0.05). In conclusion, aging and reduced HA synthesis independently impaired GC integrity. As a result, mechano-sensing and -transducing property of GC was disturbed and further diminished by HYAL activity. In addition, endothelial function was impaired with aging and further exacerbated after a reduction in HA synthesis. Funded in part by awards from National Institutes of Health Awards R01 AG060395, R01 AG077751, R01 AG076748, T32 HL007576, T32 HL139451, Veteran's Affairs Merit Review Award I01 BX004492 and Nora Eccles Treadwell Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Role of Leptin in Regulating Renal Phosphate Transport

Elevated plasma phosphate (Pi) levels, known as hyperphosphatemia, are associated with an increased risk of cardiovascular complications and mortality. Although studies have suggested a correlation between obesity and hyperphosphatemia/phosphate toxicity, the root cause of this observation has not been established. Since hyperleptinemia was also found to be associated with abnormalities in bone structure, we hypothesized that effects on renal Pi transport are responsible for this observation. To address this question, we studied hyperleptinemic mice (db/db, n=14) and compared them to wild-type mice (WT, n=10). Blood and urine samples, as well as kidney tissues, were collected and analyzed. Body weight was approximately twice as high in db/db compared to WT mice (59±3 vs. 30±2 g, P<0.05). Plasma Pi levels in db/db mice were significantly greater (~1.5-fold) compared to WT mice (2.6±0.1 vs. 1.7±0.1 mmol/L, P<0.05). However, urinary Pi /creatinine ratios were similar between genotypes. Plasma Ca2+ levels in db/db mice were significantly higher compared to WT mice (2.68±0.03 vs. 2.48±0.03 mmol/L, P<0.05) alongside urinary Ca2+/creatinine ratios being significantly higher in db/db mice compared to WT mice (1.6±0.4 vs. 0.3±0.1 mmol/mmol, P<0.05). Plasma parathyroid hormone (PTH, regulating Pi and Ca2+) levels were similar in both genotypes. The phosphaturic hormone fibroblast growth factor 23 (FGF23), which is produced and released from bone, was slightly but significantly elevated in db/db compared to WT mice (254±12 vs. 227±18 pg/mL, P<0.05). Bone formation markers (osteocalcin and procollagen type I N-propeptide) and bone resorption markers (tartrate-resistant acid phosphatase 5b and C-terminal telopeptide of type I collagen) were similar between genotypes, indicating that Pi and Ca2+ release from bone may not be causing these mineral differences. To determine the role of the kidney for the development of hyperphosphatemia, we performed 32P radiotracer studies in acutely isolated renal brush border membrane vesicles. Sodium-dependent 32P transport was not significantly different between genotypes. To determine the ambient in vivo contribution of the Na+-Pi cotransporter Npt2a, we employed acute pharmacological inhibition with PF-06869206 (Npt2a inhibitor, 30 mg/kg b.w, n=7) or vehicle (n=11) and compared plasma Pi before and 2 hours after administration in db/db mice. Vehicle treatment slightly increased plasma Pi levels compared to baseline (2.6±0.1 vs. 2.1±0.1 mmol/L, P<0.05); in contrast, the Npt2a inhibitor significantly reduced (~50%) plasma Pi levels compared to baseline (1.3±0.1 vs. 2.5±0.1 mmol/L, P<0.05). In summary, our study demonstrates that hyperphosphatemia in db/db mice is not caused by changes in renal Pi transport or bone turnover, suggesting that possibly intestinal mechanisms are responsible for increased Pi, and possibly Ca2+, absorption. Of note, Npt2a inhibition was effective in reducing hyperphosphatemia in db/db mice, indicating a potential therapeutic strategy. This work was supported by a VA Merit Review Award IBX004968A (to Dr. Rieg) and a Pilot Project from the USF Microbiomes Institute (to T.R. and J.D.R). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

GPX4 Over-expression Is Associated with Increased Senescence Burden and Metabolic Dysfunction

Chronic inflammation is a hallmark of obesity, diabetes, and cardiovascular disease (CVD), contributing to morbidity and mortality worldwide. Adipose tissue inflammation is commonly observed in obesity-related diseases and is considered a critical driver of metabolic dysfunction. Cellular senescence, a state of cell cycle arrest, accumulates in adipose tissues in obesity and contributes to tissue inflammation through the production of pro-inflammatory factors known as the SASP (senescence associated secretory phenotype). Novel therapeutics targeting senescent cells have been shown to improve metabolic function in obesity, although the underlying mechanisms of senescent cell accumulation and clearance are not well known. Here, we compared a genetically modified mouse model that overexpresses glutathione peroxidase 4 (GPX4), with wildtype (WT) littermate mice. GPX4 is an antioxidant, selenoenzyme, and a key regulator of ferroptosis, an iron-dependent form of regulated cell death. Previous in vitro studies have shown that activation of ferroptosis through inhibition of GPX4 is associated with a decrease in senescence burden, suggesting that ferroptosis may serve as a novel senolytic pathway. We hypothesized that overexpression of GPX4 in the transgenic (TG) mice will reduce ferroptosis, increase senescence burden, and impair metabolic function compared to WT mice. To determine the effects of ferroptosis on metabolic function, GPX4 WT and TG mice were fed either a 60% high fat diet (HFD) or normal chow (NC) ad libitum for 8-10 weeks. We found higher body, liver, and white adipose tissue (WAT) mass in GPX4 TG compared to WT mice fed NC and HFD (Interaction all p<0.0003, 0.0001, 0.0044, n=8-10/group). After HFD, T cell infiltration in the WAT was higher in GPX4 TG mice compared to WT (Interaction all p<0.0253), and both CD8 and CD4 were significantly different from NC controls, contributing to metabolic dysfunction in these animals (p=0.027,0.207, n=4/group). Mice fed HFD demonstrated increased glucose intolerance compared to NC controls (p=0.029, p=0.0216, n=8-12/group), however, the TG HFD mice were trending towards higher glucose intolerance compared to WT HFD (p=0.17). Compared to NC and HFD fed WT mice, there was increased gene expression for the senescence markers, p16 (all p<0.0041) and p21(all p<0.002), as well as increased expression of SASP factors, CXCL2 (all p<0.0055), TNFa (all p<0.0159), and PAI1 (all p<0.05, n=5-7/group) in the HFD fed TG mice, indicating increased senescence burden in the TG HFD mice. Malondialdehyde (MDA), a byproduct and marker of ferroptosis, was elevated in the HFD fed WT mice (p=0.0002) compared to all other groups, indicating increased ferroptosis. HFD fed TG mice also had increased expression of ferritin (all p<0.0079, n=5/group) compared to all other groups, suggesting resistance to ferroptosis that may contribute to the increased senescence burden in the TG HFD group. Together these data demonstrate that increases in cellular senescence and impairments in metabolic function after HFD are exacerbated by increased GPX4 expression, suggesting that GPX4 may be a novel target to decrease senescence and improve metabolic function through induction of the ferroptosis pathway. Funded in part by awards from National Institute of Health Awards R01 AG 060395, R01 AG048366, T32 HL139451-05, T32 HL007576, R01 AG077751, Nora Eccles Treadwell Foundation (NEFT), and Veteran's Affairs Merit Review Award I01 BX004492. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Best Reviewers Award for 2023

Best Reviewers Award for 2023

Mitochondrial function in lungs of rats with different susceptibilities to hyperoxia-induced Acute Respiratory Distress Syndrome (ARDS)

Objective: Rat exposure to hyperoxia is a well-established model of human ARDS. Adult rats exposed to hyperoxia (100% O2) die from respiratory failure within 60-72 hours. However, rats preconditioned by exposure to >95% O2 for 48 hrs followed by a 24-hr “rest period” in room air (H-T) acquire tolerance of the otherwise lethal effects of exposure to 100% O2. In contrast, rats preconditioned by exposure to 60% O2 for 7 days (H-S) become more susceptible to 100% O2. The objective was to evaluate lung tissue mitochondrial bioenergetics in H-T and H-S rats. Methods: Adult rats were exposed to room air (normoxia), >95% O2 for 48 hrs followed by exposure to room air for 24 hrs (H-T), or 60% O2 for 7 days (H-S). Mitochondria were isolated from lung tissue and used to assess mitochondrial bioenergetics. Expressions of electron transport chain complexes were measured in lung tissue homogenate using western blot. Isolated perfused lungs (IPL) were used to determine pulmonary vascular endothelial filtration coeffcient ( Kf) as a measure of pulmonary vascular permeability, and lung tissue mitochondrial membrane potential (ΔΨm). Results: Western blot shows decreased (38%) complex I expression, but increased (70%) complex V expression in H-T lung tissue homogenate compared to normoxia. Complex I expression decreased (43%) in H-S lung tissue homogenate. State 3 oxidative phosphorylation (OxPhos) capacity (Vmax) and respiratory control ratio decreased in mitochondria isolated from H-S lungs. Vmax increased in mitochondria of H-T lungs. Time for ΔΨm repolarization following ADP-stimulated depolarization increased in mitochondria isolated from H-S lungs. IPL studies revealed that tissue ΔΨm is unchanged in H-S and H-T lungs compared to normoxics. Furthermore, complex I plays the dominant role in ΔΨm in H-T and normoxia lungs with no contribution from complex II, whereas complex II has a larger contribution to ΔΨm in H-S lungs than in H-T or normoxia. Kf increased (+178%) in H-S, but not H-T lungs. Discussion: For H-T lungs, decreased complex I expression is countered by increased complex V expression, which could also account for increased Vmax. This along with high tissue glutathione content protects mitochondria from stress such as exposure to 100% O2. For H-S lungs, the effect of decreased complex I expression on lung tissue ΔΨm is countered by a larger contribution from complex II. However, higher dependency of ΔΨm on complex II could lead to higher mitochondrial oxidant production since complex II is the main source of oxidants in rat lungs. This along with decreased Vmax and increased Kf make H-S rats more susceptible to stress such as exposure to 100% O2. These results are clinically relevant since exposure to hyperoxia is a primary therapy for patients with ARDS, and ventilation with 60% O2 is often required for prolonged periods of time, particularly with COVID-19. This study was funded by NHLBI grant 2R15HL129209-03, Department of Veterans Affairs Merit Review Award BX001681, and NSF grant DMS 2153387. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lack of Renal NHE1 Exacerbates Lithium-Induced Nephrogenic Diabetes Insipidus

The sodium-hydrogen exchanger isoform 1 (NHE1) is a transporter with roles in transepithelial Na+/H+ transport, intracellular pH (pHi), and cell volume regulation. Within the kidney, we localized NHE1 to the basolateral membrane of the distal parts of the nephron and collecting duct (co-labelling with AQP2 for principal cells and H+-ATPase B1 subunit for all 3 types of intercalated cells: type A, B, and non-A-non-B). We have previously shown that lack of NHE3 does not affect Li+ clearance, and other studies have shown that NHE1 transports Li+ preferably compared to NHE3. Therefore we hypothesized that NHE1 plays a critical role in Li+-induced nephrogenic diabetes insipidus. To address this question, we used newly generated mice which lack NHE1 protein in the tubule/collecting duct system (NHE1KS-KO) of the kidney. After baseline measurements, control (n=12) and NHE1KS-KO (n=9) mice were switched to a Li+-containing diet (0.2% LiCl [40 mmol/kg], Harlan Teklad, TD09326) for 4 weeks. Urine osmolality was not different between groups under baseline conditions (control: 2641±178, NHE1KS-KO: 2716±244 mmol/kg). In response to Li+, urine osmolality reached a minimum after 7 days that was sustained until the end of the experimental period. Of note, urine osmolality was ~500 mmol/kg lower in NHE1KS-KO versus control mice (1125±170 versus 475±94 mmol/kg, P<0.05) despite genotypes having comparable plasma Li+ concentrations (0.48±0.1 versus 0.45±0.1 mmol/L). Plasma Na+ concentrations were not significantly different under baseline conditions (149±0.5 versus 148±0.4 mmol/L) but increased to a significantly greater extent in NHE1KS-KO versus control mice (156±1.9 versus 152±0.5 mmol/L, P<0.05). Along those lines, plasma Cl− was significantly greater in NHE1KS-KO versus control mice at the end of the experimental period (117±1.9 versus 111±0.4 mmol/L, P<0.05). Taken together, our data indicate that NHE1 in principal cells plays an important role in the development of nephrogenic diabetes insipidus as well as the development of hypernatremia and hyperchloremia. This work was supported by a VA Merit Review Award IBX004968A (to Dr. Rieg) and a Pilot Project from the USF Microbiomes Institute (to T.R. and J.D.R). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

MitoQ Treatment Mitigates Senescence Burden in DOXO-Induced Senescent Endothelial Cells Through Reductions in mtROS and DNA Damage

Cardiovascular toxicity is one of the adverse consequences of chemotherapy that limits treatment. Specifically, chemotherapeutics such as doxorubicin (DOXO) can lead to endothelial dysfunction through the induction of reactive oxygen species (ROS) and mitochondrial ROS (mtROS) production. MtROS are chemically reactive molecules generated as byproducts of oxidative phosphorylation during mitochondrial respiration. DOXO exacerbates its cardiotoxic effects by amplifying mtROS production, leading to an increase in DNA damage and cell senescence, particularly in endothelial cells (ECs). MitoQ is a mitochondria-targeted antioxidant designed to accumulate within the mitochondria and mitigate oxidative damage by neutralizing mtROS. However, whether MitoQ can rescue mtROS-induced DNA damage and senescence remains elusive. Here, we tested the hypothesis that MitoQ will attenuate DOXO-induced mtROS thus blunting DNA damage and subsequent EC senescence. Human umbilical vein endothelial cells (HUVECs) were simultaneously subjected to 24-hour treatments with DOXO (250nM) and MitoQ (250nM). To evaluate the antioxidative effect of the MitoQ, we examined mitochondrial superoxide using MitoSOX. The results demonstrated that DOXO increases mitochondrial superoxide by 40% (Fig1, p=0.019), whereas addition of MitoQ (MitoQ+DOXO) attenuated mitochondrial superoxide significantly compared to the DOXO group (Fig1, p=0.033). Gene expression of senescence markers, p16 and p21, and Senescence Associated Secretory Phenotypes (SASPs) factors were also examined to assess the effect of MitoQ on senescent endothelial cells. p16 was significantly reduced in the MitoQ+DOXO treatment group compared to the DOXO alone (Fig2, p=0.0090). MitoQ+DOXO lowered p21 expression by 35%, although this difference did not reach significance (Fig2, p=0.340). Moreover, MitoQ+DOXO reduced the SASP factors, IL-8, IL-6 and MCP-1, by more than 54% in comparison to the DOXO group (Fig2, all p≤0.027). Senescent endothelial cells were examined for 53BP1, a double-stranded DNA break marker, using an immunofluorescence (IF) assay. MitoQ+DOXO reduced 53BP1 by 32.6% compared to the DOXO-treated group (Fig3, p=0.011). We also assessed cell proliferation using Bromodeoxyuridine (BrdU) assay. In line with other results, the BrdU assay indicates that the proliferative capability of MitoQ+DOXO-treated cells was improved by more than 20% compared to DOXO-induced senescent cells (Fig4, p=0.008). Our findings suggest that MitoQ can mitigate DOXO-induced mtROS, attenuate DNA damage, and ameliorate senescence in endothelial cells. This provides mechanistic insight suggesting that mtROS may be a driver of cellular senescence in ECs via an increase in DNA damage and MitoQ may be an effcacious therapeutic to treat chemotherapy-induced cardiovascular toxicity. Funded in part by awards from National Institutes of Health Awards R01 AG060395, R01 AG048366, T32 HL139451, F31 AG076312, R01 AG077751, R01 AG076748, Nora Eccles Treadwell foundation (NETF), and Veteran's Affairs Merit Review Award I01 BX004492. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex differences in renal acid-base regulation

Transport along the renal tubule differs between female and male rodents, possibly as a consequence of varying abundance and expression of transporters along the nephron. For several aspects such as renal Na+ transport and blood pressure regulation, this has been comprehensively studied; however, data on sex differences in renal acid-base regulation are less well understood. We hypothesized that there will be sex differences in transporter expression profiles in response to acid-base challenges. We used female and male C57Bl/6 mice (n=10 per sex and treatment), which were challenged by acid (NH4Cl, 0.28 mM) and base (NaHCO3, 0.28 mM) in drinking water for 8 days. Blood and urine samples were collected at baseline and at the end of the experimental period before kidneys were harvested under isoflurane anesthesia. Data were analyzed by 2-way ANOVA followed by Tukey multiple comparisons test. In response to NH4Cl challenge, urine pH significantly decreased in both sexes without sex differences (male baseline: 6.4±0.1 vs. NH4Cl: 5.7±0.1; female baseline: 6.2±0.2 vs NH4Cl: 5.6±0.1). In contrast to the urinary response, blood pH was not significantly affected in male mice (male baseline: 7.29±0.01 vs. NH4Cl: 7.26±0.02); however, significantly decreased in female mice (female baseline: 7.28±0.01 vs NH4Cl: 7.22±0.02). Despite differences in acid-base physiology, no differences were observed in the abundance of NHE3, pS552-NHE3, Npt2a, NKCC2, NCC, pT58-NCC or pendrin between sexes. In response to NaHCO3 challenge, urine pH significantly increased in both sexes; however, the increase was significantly smaller in female vs. male mice (male baseline: 6.3±0.1 vs. NaHCO3: 7.6±0.1; female baseline: 6.3±0.1 vs NaHCO3: 7.0±0.3). In contrast to the urinary response, blood pH significantly increased in male mice (male baseline: 7.28±0.01 vs. NaHCO3: 7.40±0.01); however, was not significantly affected in female mice (female baseline: 7.29±0.01 vs NaHCO3: 7.31±0.01). These differences in females compared to males were associated with a significantly greater abundance of Npt2a (~1.5-fold), pendrin (~1.4-fold) and H-ATPase (~1.5-fold). No differences were observed in the abundance of NHE3, pS552-NHE3, NKCC2, NCC, pT58-NCC, between sexes. In summary, our study demonstrates that acid-base regulation shows very specific sex differences: (i) female mice seem to be more prone to a NH4Cl disturbance compared with male mice, (ii) acid challenges under these conditions do not result in major changes in the abundance of the tested proteins, (iii) male mice are more prone to a NaHCO3 disturbance possibly because of (iv) lower abundances of Npt2a, pendrin and H-ATPase. This work was supported by a VA Merit Review Award IBX004968A (to Dr. Rieg) and a Pilot Project from the USF Microbiomes Institute (to T.R. and J.D.R). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Late-life aerobic exercise reverses DNA damage and telomere dysfunction in non-atheroprone aortic regions with advanced age

Cellular senescence, a state of cell cycle arrest, contributes to arterial aging. The dominant factor driving cellular senescence is DNA damage. Moreover, telomeres, a repeated DNA sequence at the end of chromosomes, are especially vulnerable to DNA damage induced by DNA-damaging stimuli such as atheroprone shear stress. Although the adoption of aerobic exercise in later life is an effective strategy to mitigate arterial aging, its direct relationship with DNA damage and telomere dysfunction has yet to be elucidated. Additionally, the impact of late-life aerobic exercise, particularly in regions exposed to atheroprone and non-atheroprone shear stress, may not yield uniform benefits, requiring further exploration. We sought to investigate the effects of late-life aerobic exercise on DNA damage and telomere dysfunction in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in aortic regions exposed to distinct shear stress patterns such as the major aortic arch, minor aortic arch, and thoracic aorta. Fifteen male C57BL6 (22-23 mo) were given access to voluntary running wheel (VWR) for 4 weeks. They were classified as high-running (HR), moderate-running (MR), and low-running (LR) groups based on their habitual VWR distances (n=5 per group). Habitual VWR distance was greater in HR and MR compared to LR (75.9±11.2 and 21.3±1.6 vs. 5.8±2 m/day; P≤0.0003). Maximal treadmill running distance improved in HR, did not change in MR, and diminished in the LR (HR, MR vs. LR; P≤0.035) and was correlated to habitual VWR distance at 1-month post-intervention (R2=0.252, P=0.056). Immunofluorescence-fluorescent in situ hybridization was performed to detect the abundance of 53BP1 foci, a marker of DNA damage, and colocalization to telomeres, a measure of telomere-specific DNA damage known as telomere dysfunction-induced foci (TIF). The percentage of ECs containing 53BP1 foci and TIF was lower in the non-atheroprone aortic regions, i.e. major aortic arch and thoracic aorta, of HR compared to LR (P≤0.002), but there was no difference in the atheroprone, i.e. minor aortic arch (P≥0.899). A strong to moderate correlation was observed between 53BP1 foci and habitual VWR distance in major aortic arch and thoracic aorta (R2=0.584 and R2=0.54, P≤0.002) but only between VWR and TIF in the thoracic aorta (R2=0.356, P=0.019). The 53BP1 foci and TIF in VSMCs were comparable across groups in all aortic regions (P≥0.102). Likewise, Telomere length in ECs and VSMCs were similar across groups regardless of aortic region (P≥0.296). In conclusion, our findings suggest that increased level of habitual aerobic exercise in later life has a beneficial impact on DNA damage and telomere dysfunction in ECs, particularly in aortic regions exposed to extended periods of non-atheroprone shear stress. Notably, the volume of aerobic exercise was inversely associated with DNA damage and telomere dysfunction. These effects were independent of telomere length. The improvement in DNA damage and telomere dysfunction associated with habitual aerobic exercise were specific to ECs, as VSMCs remained unaffected in all aortic regions and results were independent of telomere length. Funded in part by awards from National Institutes of Health Awards R01 AG060395, R01 AG077751, R01 AG076748, T32 HL007576, T32 HL139451, Veteran's Affairs Merit Review Award I01 BX004492 and Nora Eccles Treadwell Foundation. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Peer Reviewer Award

Peer Reviewer Award

Best Reviewers Award for 2023

Best Reviewers Award for 2023

Reviewer acknowledgments and awards: Recognition awards for distinction of reviewing in 2023

In 2023, members of the Mechanism and Machine Theory journal's Editorial Board and many independent reviewers contributed their time and expertise in reviewing manuscripts. This process greatly benefits our editors, contributing authors, and ultimately our readers. In fact, the high standard and reputation of the journal is strongly shaped by the expert knowledge, generous time contribution, and commitment to mechanism and machine science of the body of reviewers. Both, Elsevier, the publisher, and the editor-in-chief of the journal, would like to publicly pay tribute to all of the 824 reviewers who completed a total of 2118 reviews during the year of 2023. We are extremely grateful for their outstanding contributions and we are look forward to working with them in 2024!

Viewpoint: the evolving landscape of peer review

PurposeThe purpose of this viewpoint is to spotlight the role of reviewers within the collaborative triad of academic publishing. It argues that the significance of reviewers is often disregarded, leading to a gap in our understanding of the peer review process. This perspective emphasizes reviewers as unsung heroes in the publishing ecosystem, providing intentional and thought-provoking insights into the less-discussed yet impactful developments in the evolving peer review landscape.Design/methodology/approachLeveraging the author’s distinguished background as a recipient of the Journal of Service Marketing Outstanding Reviewer Award, this paper offers a personal reflection and synthesised viewpoints on the peer review process. Serving as a representative voice for reviewers, it provides insightful perspectives from the vantage point of a peer reviewer, diverging from conventional editorials and commentaries authored by editors.FindingsAcknowledging the shrinking reviewer pool, this viewpoint suggests a mandatory “review for review” system alongside incentives like editorial positions, while considering financial rewards for reviewers. The rise of generative artificial intelligence (AI) in review prompts ethical concerns but offers solutions for handling diverse submissions and dealing with “Reviewer 2.” While embracing open review for its transparency, potential pitfalls surrounding article confidence and copyright require attention. Ultimately, this viewpoint advocates for a collaborative approach, valuing reviewers, exploring innovative solutions, navigating ethical dilemmas in the technological age and implementing transparent practices responsibly for the betterment of scholarly discourse.Originality/valueThis viewpoint highlights the invaluable contributions of reviewers, enriching the scholarly community and promoting intellectual growth.

The Best Paper and Best Reviewer Awards 2023

The Best Paper and Best Reviewer Awards 2023

Best Paper and Best Reviewer Awards 2023

Best Paper and Best Reviewer Awards 2023

Editorial Statistics and Best Reviewers Award for 2023.

Editorial Statistics and Best Reviewers Award for 2023.

An Empirical Study on Roles and Their Information Correlations for Interdisciplinary Peer Reviewer

Peer review has always been known as the gatekeeper for the academic quality of papers. Traditional peer review is mostly carried out in a singular discipline, while peer review for interdisciplinary scientific research must go across the boundaries of multiple disciplines, and there is a real opposition between disciplines ‘differentiation’ and ‘de-differentiation.’ Due to this opposition, the practice of interdisciplinary peer review has more research value. Through an empirical study using Publons data, this article introduces the role theory from sociology as a theoretical support, studies role characteristic information of interdisciplinary peer reviewers, extracts their roles, measures the gaps between the roles according to their correlations, and proposes countermeasures to narrow the gaps through role construction to improve the quality of peer review in general. Specifically, this study adopts the empirical analysis method to obtain the behavioural characteristics data of the reviewers in the top 1 per cent in Cross-Field of the Global Peer Review Awards in 2018 and 2019 from the Publons platform and uses the exploratory factor analysis method to extract the roles of the reviewers. Using structural equation modelling to fit the role information association model, the authors compare and analyse the data models of 2018 and 2019 by using the comparative analysis method. The results found are as follows: The ‘researcher’ role, ‘reviewer’ role, and ‘editor’ role are all positively correlated, and the correlations are getting higher. It indicates that the correlations between the three are getting stronger, which will make transitioning between roles less difficult.

JACIII Distinguished Editor & Outstanding Reviewer Awards 2023

The JACIII Distinguished Editor and Outstanding Reviewer Awards were established for the purpose to honor editors who have made a significant contribution to the growth of the JACIII in 2018 and to acknowledge reviewers who have made a significant contribution to reviewing in 2022. We express our deepest gratitude for their professional work, which we believe conductive to development of not only the JACIII but also scientific research.