bluuebunny/crossref_metadata_2025_split huggingface dataset:
No effect of anti‐hypertensive treatment during the metaboreflex in patients with essential hypertension
Authors: crisafulli antonio , Roberto Silvana , Milia Raffaele , Doneddu Azzurra , Ghiani Giovanna , Magnani Sara , Pinna Virginia , Mulliri Gabriele , Olla Sergio 
Published: April 2020

In healthy subjects (HS), when the muscle metaboreflex (MM) is activated, the target mean blood pressure (MBP) is reached thanks to cardiac output (CO) increments, whilst systemic vascular resistance (SVR) plays a minor role
1. Differently, in essential hypertension (EHT) hemodynamics during the MM has been often reported to be dys‐regulated, with exaggerated SVR response (i.e. arteriolar vasoconstriction) and reduced CO
2. We tested the hypothesis that standard anti‐hypertensive treatment could improve this abnormal hemodynamics. 20 patients in pharmacological treatment for EHT (10 females; age 54.5±10.4 yrs, time since diagnosis 8.5±6.9 yrs) participated in this study together with a control group of 20 age‐matched HS. At baseline (BAS), they underwent randomly assigned the following protocol to study the MM activity: 1) post‐exercise muscle ischemia (PEMI), and 2) control exercise recovery CER) test. Exercise was dynamic handgrip performed at 30% of the maximum previously assessed. The EHT group performed again the test at least 7 days later (interval 7–15 days) after pharmacological wash‐out (WHT). Response to the MM for each cardiovascular parameter was assessed as PEMI minus CER level. Hemodynamic variables were evaluated by impedance cardiography. Results demonstrated that in EHT, SVR response did not change at the BAS and at the WHT (338.0±452.7 vs. 371.8±465.3 dynes•s‐1•cm‐5 at BAS and at WHT respectively). Moreover, EHT showed higher SVR response than HS (20.9±399.6 dynes•s‐1•cm‐5, p<0.05 vs. both the BAS and the WHT test). However, the MBP response was similar between groups and conditions. Likewise CO was not different between groups. It was concluded that the anti‐hypertensive treatment was not able to counteract the arteriolar vasoconstriction and the increased SVR response experienced by ETH patients during the MM. Further study is warranted to better understand what causes the hemodynamic abnormalities of EHT patients during the MM activation.Support or Funding InformationThis study was supported by the University of Cagliari and the Italian Ministry of Scientific Research.
Modulation of Aquaporin 2 by Renin‐Angiotensin‐Aldosterone System Peptides in Medullary and Cortical Collecting Duct Cells
Authors: Da Silva Braga Tamires , de Oliveira Lilian Caroline Gonçalves , Casarini Dulce Elena 
Published: April 2020

The kidney is responsible for the body water balance and homeostasis. The collecting duct system is important for this role due its responsibility, as water reabsorption and urine production. In the collecting ducts cells, it’s known that the reabsorption of water is made by the water channels named aquaporins, specially aquaporin 2 and aquaporin 3. In those channels the reabsorption is controlled by the peptide hormone vasopressin which induces the water transport due the water channels. Into the homeostatic mechanism, there is the renin‐angiotensinaldosterone system (RAAS) which regulates the water and sodium absorption as well. Previous studies of our group described that Ang 1‐7 and Ang II are inductors to the migration of AQP2 to the membrane in LLC‐PK1 cells. Therefore, the aim of this study is to evaluate if the RAAS peptides, Angiotensin II (Ang II) and Angiotensin 1‐7 (Ang 1‐7), are capable to induce water reabsorption due aquaporin 2 in Inner medullary collecting duct cells (IMCD) and cortical collecting duct cells (M1).MethodsIn this present study we evaluate the expression of aquaporin 2 after the treatment with Ang II and Ang 1‐7in different times (5,15 and 30 minutes) in both cells of the collecting duct system (medullary and cortical). The analysis of the expression was made by western blotting assay.ResultsThe western blot technique showed that in both cellular types, there is a difference between the expressions in the cells. M1 cells have showed that after different treatments times, the RAAS peptides decrease the expression of aquaporin 2 differently of the IMCD cells, that showed expression of aquaporin 2 increased when treated with Ang II. In conclusion, the results demonstrated that Ang II and Ang 1‐7can modulate the water channel aquaporin 2 expression.Support or Funding InformationCAPES, FAPESP and CNPq
The Effects of Diet on Hard Palate Morphology in Humans
Authors: Bushman Jeness , Maddux Scott D. , Menegaz Rachel A. 
Published: April 2020

With the Neolithic adoption of agricultural practices around 10,000 BCE came a dietary transition from foraged foods to domesticated crops. A significant reduction in the overall dimensions of the human craniofacial skeleton is attributed to the decreased biomechanical demands associated with agricultural diets. However, the impact of this dietary transition on specific skeletal structures such as the hard palate is poorly understood. Previous experimental work has shown that laboratory rabbits fed a soft, processed diet have a vertically shallow palate with decreased cortical bone thickness and trabecular area. Here we test the hypothesis that compared to hunter‐gatherer populations, human agriculturalists have a similarly reduced palate due to the consumption of softer, more intensely processed foods.CT scans from a mixed‐sex adult sample of Homo sapiens skulls (n=36) representing two pre‐industrial agricultural groups (ancient Egyptians and pre‐Columbian Peruvians) and two hunter‐gatherer groups (indigenous Australians and native Alaskans) were analyzed using 3D Slicer software. The following dimensions were measured at the anterior, middle, and posterior palate: palate width; vertical palate depth; cortical bone thickness along the oral lamina; and trabecular bone area. Palate variables were analyzed using pairwise Mann‐Whitney U‐tests (α = 0.05). Results show that compared to hunter‐gatherers, individuals from agricultural populations have significantly vertically shallow palates, thinner cortical bone at the middle and posterior palate, and decreased trabecular bone area at the middle palate.These results support the hypothesis that cross‐sectional palatal morphology is associated with the biomechanical profile of the human diet, and that the hard palate of modern humans has been significantly affected by the adoption of agriculture. The adoption of agriculture decreased the mechanical strain experienced by the hard palate, resulting in a decrease in overall bone volume. We propose that further changes might be expected in palate morphology in more recent human populations, related to increased food processing and reduced dietary breadth seen during the Industrial and Green Revolutions of the mid‐17th through 20th centuries. Additional research is needed to investigate the effect of industrialized agriculture on palatal morphology, as well as the influence of biomechanical loading on the hard palate across life history and growth.Support or Funding InformationFunding was provided by the American Association for Anatomy Innovations Program.
Characterization of EfhX, a calcium sensor protein in Xanthomonas required for elicitation of the hypersensitive response in Solanum species
Authors: Quay Juliana , Hurlbert Jason 
Published: April 2020

We have identified a gene in several strains of Xanthomonas that, when expressed, can elicit a hypersensitive response (hr) in tomato plants. Hr elicitation is normally limited to specific bacterial‐host pairings, but introduction and expression of this gene by bacterial species that do not normally infect tomato serves to elicit hr, indicating that the encoded 170 amino acid protein is crucial to the infectious process. Bioinformatic analysis of the protein, which we have named EfhX (
EF‐
hand containing protein from
Xanthomonas) reveals that the protein is predicted to contain a domain of unknown function spanning the amino terminal region, a single transmembrane alpha‐helix spanning amino acids 60 to 81 and two putative EF‐hand calcium binding domains in the carboxy‐terminal domain of the protein. In order to better understand the function of this novel protein, we have cloned the EfhX gene from Xanthomonas aurantifolia and expressed it in Escherichia coli. We have successfully purified the protein to homogeneity as determined by SDS‐PAGE, anti‐hexahistidine Western Blot and MALDI‐TOF mass spectrometry. Using the purified protein, we have used isothermal titration calorimetry to confirm that the protein has two calcium binding sites, with one site having an affinity (Kd) for calcium of 6.75 mM and the second site having an affinity of 1 uM. We are currently performing circular dichroism spectropolarimetry and gel filtration studies to determine if the quaternary state of the protein changes upon calcium binding. Simultaneously, we have initiated crystallization trials of the purified protein to identify solution conditions suitable for growth of crystals for x‐ray diffraction experiments so that the structure of the protein can be determined.Support or Funding InformationThis work is supported by grants from the National Center for Research Resources (5 P20 RR16461) and the National Institute of General Medical Sciences (8 P20 GM103499) from the National Institutes of Health.
Mice but not rats modulate liver mitochondrial machinery in chronic hypoxia
Authors: Reyes Christian Arias , Joseph Vincent , Soliz Jorge 
Published: April 2020

Mice (FVB) permanently living at high‐altitude have increased respiratory frequencies and sustained or increased metabolic rates. On the other hand, rats permanently living at high‐altitude (SD) have impaired respiratory control, high hematocrit and hemoglobin, signs of pulmonary hypertension, and reduced metabolism; all these considered to be detrimental. This is coincident with the fact that common rats are not found in natural high‐altitude environments. At sea level, we reported that mice, but nor rats, exposed to 21 days of hypoxia (12% O2) increase their metabolic rate (O2 consumption and CO2 production), similarly to other rodent species that are considered well adapted to high‐altitude. As mitochondria is the final user of O2 in metabolism, we were interested in the role of mitochondria behind this divergence in physiological adjustments. We used saponin‐permeabilized samples of liver (most energy‐consuming organ in rodents), from male adult FVB mice and SD rats after exposure to hypoxia (12% O2, for 0, 1, 7 or 21 days), to measure the mitochondrial O2 consumption rate (OCR) following the SUIT‐01 protocol in the high‐resolution respirometer O2K (OROBOROS instruments). OCR was measured with substrates activating the NADH, succinate , and fatty acid pathways of the electron transport chain (ETC). We also measured the maximum capacity of ETC by uncoupling the electron transport from the oxidative phosphorylation with CCCP. The level of activation of complexes I and II was reported as the OCR for the N or S pathway correspondingly, divided by the maximum capacity (flux control ratio).Our preliminary results show that, compared to rats, mice have significantly higher ETC maximum capacities in normoxia and hypoxia. Moreover, after 21 days of hypoxia, mice showed an increase of 43% in maximum capacity in comparison to normoxic controls, while no increase in maximum capacity was evidenced in rats. In mice, we observed that complex I is transiently hyperactivated after 1 day of hypoxia and then, its activity reduces down below control levels by day 21 of hypoxia. Contrastingly, complex II activity is reduced after one day of hypoxia, getting back to control levels by day 21 of hypoxia. Furthermore, in rats, an increased activity of complex I occurred after 21 days of hypoxia. Regardless of normoxic or hypoxic exposure, rats showed higher activation levels of complex II than mice.These results show that mice, but not rats, have the ability to modulate their liver metabolic mitochondrial machinery under chronic hypoxia. The higher and adjustable maximum capacity in mice, suggest a more powerful and plastic liver mitochondrial machinery than in rats. This might explain in part their ability to keep sustained metabolic rates under hypoxic conditions.Support or Funding InformationSupported by NSERC, the Health Respiratory Network of Québec and CIHR.
Dynamics of nerve dependence during the regeneration of axolotl salamander limbs
Authors: Jeon Eun Kyung , Monaghan James 
Published: April 2020

When nerve supply is severed at the brachial plexus, regeneration of Axolotl salamander limbs ceases. Nerves provide specific molecules that help initiate and sustain the process of regeneration. Regenerating limbs show different responses to denervation at each step of the process. Severing nerves right after amputation prevents further growth, but denervation post‐growth of a regenerative tissue yields a miniature limb. Nerves may be providing molecules that maintain cell plasticity, but how regenerative tissue changes in absence of nerves is unknown. In this study, effect of denervation on cell proliferation at each point of regeneration is investigated. Regenerating limbs were denervated one day before collection and labeled with 5‐ethynyl‐2’‐deoxyuridine (EdU, a proliferation marker) in vivo‐3 hours before collection. We show region‐specific depletion of proliferation in limbs 0 (uninjured), 6, 9, 12, 15, 18, and 25 days post amputation. Our results suggest that loss of nerve supply drastically reduces proliferation in both uninjured and regenerating limbs but not in tissue actively undergoing digit formation.Support or Funding InformationThis project was supported by Matz Scholarship in Biotechnology and NSF grants 1558017 and 1656429.
Implication of RAGE Signaling in establishing models of COPD pathogenesis
Authors: Reynolds Paul R. 
Published: April 2020

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States and it is characterized by inflammation and respiratory tissue loss. Tobacco smoke is the major cause of COPD. Studies identified
receptors for
advanced
glycation
end‐products (RAGE) as a smoke‐induced pattern recognition receptor with potent pro‐inflammatory characteristics and we’ve observed increased pulmonary RAGE following first and secondhand smoke (SHS) exposure. Further, RAGE transgenic mice that conditionally increase RAGE expression manifest COPD characteristics and are possible smokeless models of a smoker’s lung. We evaluated inflammatory effects of SHS with and without semi‐synthetic glycosaminoglycan ethers (SAGEs), a family of anionic, partially lipophilic sulfated polysaccharide derivatives that inhibit RAGE signaling. The current research evaluated the in vivo effects of short‐term smoke exposure in RAGE null, conditional RAGE over‐expressing, and control mice via a nose‐only exposure platform for 4 weeks (Sireq Scientific) and compared them to animals exposed to room air. Groups of mice were also co‐treated with SAGEs via weekly ip injections (a 30mg/kg body weight). Molecular characterization of smoke exposure revealed significant pulmonary inflammation and apoptosis mediated in part by RAGE. Inflammatory cell behaviors were assessed by determining the activation of Ras, intracellular signaling kinases, and cellularity/cytokine secretion in bronchoalveolar lavage fluid (BALF). Inflammatory signaling intermediates and cytokine elaboration were induced by SHS and influenced by the availability of RAGE, as evidenced by RAGE targeted mice and SAGE treatment. We also observed compromised lung mechanics mediated by RAGE expression during exposure. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to tobacco smoke and implicates plausible therapeutic modalities that may attenuate lung pathology.Support or Funding InformationThis work was supported by a grant from the Flight Attendant’s Medical Research Institute (FAMRI).
Impact of Transcriptional Dysregulation on the DNA Damage Response in Ewing’s Sarcoma
Authors: Rollins Matthew Gregory 
Published: April 2020

Ewing’s sarcoma is a soft‐tissue bone malignancy characterized by a translocation event wherein the N‐terminal low complexity domain of EWSR1 is fused with the DNA binding domain of the ETS transcription factor Fli1. The resulting EWS‐Fli1 fusion protein drives expression of oncogenes and knockdown of tumor suppressor proteins. More specifically, EWS‐Fli1 acts as transcriptional regulator by helping recruit RNA Pol II to promoter regions, which is subsequently phosphorylated by CDK9 to escape initiation into elongation. Interestingly, Ewing’s sarcoma is particularly susceptible to chemotherapy compared to other cancers; however, the underlying reason for this sensitivity to DNA damage has not been elucidated. Given EWS‐Fli1’s role in disrupting transcription, it was hypothesized EWS‐Fli1 is concurrently disrupting the DNA damage response. Here, a combination of CDK9 inhibition with DNA damage was found to drastically diminish cell viability in Ewing’s cell lines but not in non‐Ewing’s osteosarcoma or HEK293 cells. Ordinarily, after DNA damage γH2A.X phosphorylation occurs on histones near sites of damaged DNA early during the DNA damage response to signal DNA damage repair initiation. Further work has shown Ewing’s cells undergoing the combination treatment above have a marked decrease in this DNA damage marker γH2A.X as compared to non‐Ewing’s cells. Together, these results suggest Ewing’s sarcoma cells are sensitized to DNA damage due in part to transcriptional dysregulation.Support or Funding InformationFunding for this research provided by the American Cancer Society and NIH.
Co‐expression of placental RAGE and g‐H2AX during intrauterine growth restriction and preeclampsia in rodents
Authors: Tsai K.Y.F. , Hirschi-Budge K. M. , Davis T. , Llavina S. , Fowers R. , Reynolds Paul R. , Arroyo J. 
Published: April 2020

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are obstetrics complications associated with poor outcomes for the both the mother and fetus. Although both characteristically differ, both diseases are associated with placental malfunction that stems in part from increased placental apoptosis. DNA double strand breaks (DNA‐DSBs) represent some of the most destructive forms of genomic damage in which both strands of DNA are ruptured. H2AX is a component of the histone octomer and is phosphorylated to form g‐H2AX in response to the sensing of DNA‐DSBs. The receptor for advanced glycation end‐products (RAGE) is a multi‐ligand receptor primarily expressed on cell membranes, where it functions as a progression factor in inflammatory signaling; however, the nuclear isoform of RAGE (nRAGE) has been described as having a crucial role in DNA‐DSBs repair. The purpose of this study was to identify placental DNA damage, placental nRAGE and g‐H2AX expression in a secondhand smoke exposed rodent model of IUGR and a Gas6 induced PE model. Placental and fetal weights were determined at the time of necropsy in the IUGR model. Blood pressure and proteinuria was assessed in the PE model. Characterizing DNA degradation was used to confirm placental DNA damage during these pregnancy complications. Immunohistochemistry was used to determine localization of both molecules in the placenta. Relative to controls we observed: 1) decreased placental and fetal weights (1.4‐fold and 2.3‐fold; p<0.003) during IUGR; 2) significantly increased systolic and diastolic blood pressure and proteinuria (80%; p<0.05) during PE; 3) increased DNA degradation in the IUGR and PE placentas and 4) Increased staining for RAGE and g‐H2AX in the IUGR and PE placentas. These results may provide insight into the physiological relevance of these molecules, and if so, their modification during gestation may help alleviate placental disease.Support or Funding InformationThis work was supported by a grant from the Flight Attendant’s Medical Research Institute (FAMRI, PRR and JAA) and a BYU Mentoring Environment Grant (JAA and PRR).
Cardiac‐specific Deletion of Filamin C Decouples Myocyte Contractility and Calcium Handling in Adult Mice
Authors: Powers Joseph D. , Liu Canzhao , Fang Xi , Omens Jeffrey H. , Chen Ju , McCulloch Andrew D. 
Published: April 2020

Costameres are sub‐membranous protein complexes in striated muscle that play roles in mechanical signal transduction and force transmission between the Z‐disc of the sarcomere and the extracellular matrix. In cardiac myocytes (CMs), the cytoskeletal protein Filamin C (FLNC) interacts with multiple proteins in the Z‐disc and the costamere, suggesting that it contributes to costamere‐based mechanotransduction in the heart. Moreover, mutations in the gene that encodes FLNC have been associated with multiple forms of human cardiomyopathies. To investigate the role of FLNC in cardiac mechanosignaling and pathological remodeling, we employed a recently developed murine model of inducible and cardiac‐specific FLNC knockout (FLNC‐icKO). Previous studies with this mouse model used echocardiographic measurements of adult FLNC‐icKO mice to reveal a severe dilated cardiomyopathy (DCM) phenotype by 2 weeks post‐induction, including significantly reduced ventricular fractional shortening. Correspondingly, we found that intact papillary muscles dissected from adult FLNC‐icKO hearts have significantly reduced twitch force compared to those dissected from wild‐type (WT) hearts. Interestingly, while the fractional shortening of isolated CMs from FLNC‐icKO hearts is also significantly reduced compared to WT CMs, the calcium transient (peak amplitude and duration) during a twitch is not different between groups. These results suggest that contractility and calcium handling in FLNC‐null hearts are decoupled. Potential mechanisms that may be responsible for this apparent decoupling are a disruption in force transmission between the sarcomere and the cell membrane, an increased myofilament lattice spacing, or altered calcium sensitivity of the myofilaments upon the deletion of FLNC in CMs.Support or Funding InformationFunding: HL007444‐36 to JDP, HL144872 to JC, and HL137100 to ADM.