bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of NKCC1 and Aquaporins 4, 7 and 9 in Mouse Choroid Plexus and Ependymal Cells
Authors: Patyal Pankaj , Alvarez‐Leefmans Francisco Javier 
Published: November 2023

Choroid plexus epithelial cells (CPECs) secrete cerebrospinal fluid (CSF) through poorly understood mechanisms involving Aquaporins (AQPs) and various solute transport proteins like the Na+/K+ pump and the Na+‐K+‐2Cl− cotransporter 1 (NKCC1). Net water movement across CPECs occurs from the basolateral membrane through the apical membrane. However, with the exception of AQP1 in the apical membrane, the molecular pathways for transepithelial water fluxes are either unknown, or their expression is controversial (Damkier et al. 2013, Physiol Rev 93, 1847). Because of their relatively high transcript expression (Cha et al, 2014, FASEB Journal 28 .1 Suppl 1182.3) the present work focuses on the cellular and subcellular localization of AQPs 4, 7 and 9 proteins in mouse CPECs and ependymal cells (EPCs), using immunolabeling with validated antibodies and confocal immuno‐fluorescence. Evidence for AQP4 expression in CPECs is controversial. The present results demonstrate that: 1) AQP 4 is expressed neither in CPECs nor in ependymal cells, but in radial glial endfeet surrounding the basal aspect of EPCs, where it is co‐expressed with NKCC1; the latter was also expressed in the apical membrane of both CPECs and EPCs; 2) AQP 7 expression was found to be restricted to the apical membrane of CPECs and EPCs. 3) AQP9 was expressed neither in CPECs nor in EPCs. The pathways for water influx across the basolateral membrane of CPECs remain to be elucidated. The pattern of expression of NKCC1 and AQP4 suggests a role of these proteins in K+ uptake from the CSF, both in CPECs and EPCs, thus regulating CSF and interstitial brain fluid [K+]. The expression of AQP7 in the apical membrane of CPECs suggests that this protein could work together with AQP1 in CSF secretion.Support or Funding Information(Supported by Wright State University Foundation FOAP 551462)
Mechanisms of Adenosine A1 Receptor‐Mediated Enhancement of Vasa Vasorum Endothelial Cell Barrier Function
Authors: Batori Robert , Kasa Anita , Shaw Mary , Sanjiv Kumar , Taraseviciene Laimute , Lapel Martin , Weston Philip , Fragoso Miguel , Moldovan Radu , Stenmark Kurt R , Verin Alexander , Gerasimovskaya Evgenia 
Published: November 2023

The vasa vasorum (VV) is a microcirculatory network that provides oxygen and nutrients to the adventitia and media of large blood vessels. Previously, we have demonstrated that angiogenic expansion of pulmonary artery (PA) VV in the chronically hypoxic calves exhibit increased permeability for circulating inflammatory cells and macromolecules. Extracellular adenosine (Ado) increased transendothelial electrical resistance (TER) of VVEC isolated from control (Denver altitude) and, in lesser extent, hypoxic (2 weeks, PB=430 mmHg) neonatal calves. Ado‐induced VVEC barrier enhancement involved activation of Ado A1 receptors (A1R), PI3K/AKT pathway, and actin remodeling. In the current study we demonstrated that inhibition of Rac1 by transduction of VVEC with dominant‐negative adenoviral Rac N17 construct almost completely abolished adenosine‐induced increase in TER supporting a critical role of Rac1 activation in Ado‐induced VVEC barrier enhancement. Inhibition of Rac1 activity also leads to the decrease of AKT phosphorylation, suggesting that Rac1 is an upstream regulator of AKT signaling in VVEC. In addition, Ado increased autophoshorylation of p21‐activated kinase 1 (PAK1), a well‐known downstream target of Rac1, reflecting its activation. Pharmacologic inhibition of PAK1 decreased basal TER and abolished Ado‐induced TER increase indicating involvement of PAK1 in VVEC barrier maintenance. Importantly, A1R expression was demonstrated in the VV of pulmonary arteries of Sprague Dawley (SD) rats, indicating that VV localization of A1R is not restricted to bovine VV. Intravenous co‐injection of Rhodamine‐conjugated Griffonia Simplicifolia lectin and FITC‐conjugated dextran in SD rats followed by two photon confocal microscopy of dissected pulmonary arteries revealed increased permeability of PA VV in chronically hypoxic SD rats. Thus, this model shows a great promise for the in vivo validation of the protective role A1R agonists in VV barrier integrity. In summary, we demonstrate for the first time that A1Rs enhance VVEC barrier function through the activation of Rac1/PAK pathway and actin cytoskeleton remodeling. We propose that A1Rs can be recognized as a vascular bed‐specific and novel therapeutic target to regulate VV barrier function and pathologic vascular remodeling in chronic hypoxia.Support or Funding InformationSupport: NIH/R01 HL086783 to EVG, PPG HL101902 to ADV
Effects of Aging on Markers of Ribosome Biogenesis in Fast‐ and Slow‐Twitch Skeletal Muscle in Rodents Aged 3 to 24 Months
Authors: Mobley Christopher Brooks , Mumford Petey W. , Kephart Wesley C. , Haun Cody T. , Holland A. Maleah , Osburn Shelby C. , Beck Darren T. , Martin Jeffrey S. , Young Kaelin C. , Kavazis Andreas N. , Lowery Ryan P. , Wilson Jacob M. , Roberts Michael D. 
Published: November 2023

OBJECTIVERibosome biogenesis is an essential process for regulating skeletal muscle mass by facilitating muscle protein synthesis. Aging results in numerous alterations in skeletal muscle; specifically, a decline in protein synthesis in skeletal muscle. However, less is known about the functional impact of the ribosome in aging skeletal muscle. Therefore, we sought to investigate the effects of sequential aging on various markers of ribosome biogenesis in fast‐ and slow‐twitch skeletal muscle in rodents.METHODSMale Fischer 344 rats (300–600 g) were sequentially aged to 3, 6, 12, 18, & 24 months (mo). Plantaris (Type II, fast‐twitch) and soleus (Type I, slow‐twitch) skeletal muscle were harvested from each respective animal and subjected to RNA isolation and analyses and Western blotting.RESULTSCompared to 3 mo old rats, plantaris ribosome content (total RNA) was 40% lower in 6 mo rats (p<0.05), 59% lower in 12 mo old rats (p<0.05), 69% lower in 18 mo old rats (p<0.05) and 55% lower in 24 mo old rats. There were no age‐related differences in soleus ribosome content. Plantaris c‐myc protein significantly paradoxically increased across age groups; specifically, 12 mo rats were 3.05‐fold greater (p<0.05), 18 mo rats were 5.28‐fold greater (p<0.05) and 24 mo old rats were 5.44‐fold greater (p<0.05) than 3 mo old rats. There were no age‐related differences in soleus c‐myc protein levels. Plantaris upstream binding factor (UBF) protein was 76% greater in 24 mo old rats versus 3 mo old rats (p<0.05). Soleus UBF was only different between the 18 mo old rats and 24 mo old rats (specifically ~3‐fold greater in 18 mo versus 24 mo old rats; p<0.05). Compared to 3 mo old rats, plantaris eukaryotic initiation factor (eIF)2Bɛ protein was 34% lower in 6 mo old rats (p<0.05), 49% lower in 18 mo old rats (p<0.05) and 68% lower in 24 mo old rats (p<0.05). There were no age‐related differences in soleus eIF2Bɛ protein levels. Plantaris eukaryotic elongation factor 2 (eEF2) was not different between age groups. Compared to 3 mo old rats, soleus eEF2 was 32% lower (p<0.05) in 18 mo rats and 66% lower in 24 mo old rats (p<0.05).CONCLUSIONAging clearly decreases ribosome content in fast‐twitch but not slow‐twitch skeletal muscle. Furthermore, there is a compensatory up‐regulation in plantaris c‐myc and UBF protein expression to potentially offset the decline in ribosome content. Identifying other intracellular mechanisms and/or co‐factors that contribute to decrements in ribosome biogenesis in skeletal muscle is warranted.Support or Funding InformationThis study is supported in part by a contract from the University of Tampa (to M.D.R. from J.M.W) as well as laboratory start‐up funds from M.D.R.
Effect of diurnal regulated‐endogenous melatonin on wound healing processes in skin injured animal model
Authors: Choi Jeonghyun , Hong Yonggeun 
Published: November 2023

To elucidate the effect of diurnal regulated‐endogenous melatonin on the wound healing after skin injury, experimental animals were divided into three groups following light/dark cycle; L/D, 12/12‐hr light/dark cycle; LL, 24/0‐hr light/dark cycle; DD, 0/24‐hr light/dark cycle. We found increased mRNA expression of tumor necrosis factor alpha (TNF‐α), which is the representative pro‐inflammatory cytokine, in DD group at 15 hr after injury. However, LL group showed increased TNF‐α mRNA expression at 7 day after injury, indicating the delayed augmentation of TNF‐α. We further found that cleaved caspase‐3 expression in LL group at 15 hr and 2 day after injury. Transforming growth factor beta1 (TGF‐β1) and extracellular signal‐regulated kinase 1/2 (ERK1/2) expression of DD group was significantly increased. In histology, more fibroblast‐like cells and adipose cells were identified in acute phase of injury. Also, we found the migration of fibroblast‐like cells and accumulation of collagen‐like fibers in DD group, which are thought to indicate acceleration of re‐epithelialization in wound healing processes. Furthermore, increased wound closure rate was identified in DD group suggesting accelerated structural recovery in wound healing processes. These finding suggest that elevated endogenous melatonin concentration induced by conditional controlled photoperiodicity might contributes to the wound healing speed and quality, which may modulated by inflammation and growth factors.Support or Funding InformationFunding: NRF‐2012R1A1A2005089, NRF‐2013R1A2A2A01067169
Critical role of Pin1 on neuronal rescue after transient ischemic brain injury
Authors: Kim Joo‐Heon , Lee Seunghoon , Hong Yonggeun 
Published: November 2023

Pin1 contains two functional domains, an N‐terminal WW domain and a C‐terminal PPIase domain. We defined a critical role of Pin1 on neuronal rescue through Pin1 inhibitor treatment after ischemic brain injury (MCAo). Juglone (Jug, 1 mg/kg), Pin1 inhibitor, was administered once a day for 7 days after MCAo. Analysis in histology, protein, and gene were used to determine neural cell death and survival pathway at day 7. MCAo+Jug group lead to significant downregulation of Bcl‐2 and Bax expression compared with MCAo+Veh group (p <.01). MCAo+Jug group was shown to reduce the levels of Pin1, Tau5, and phspho‐TauThr231 in both immunoblotting and immunostaining (p<.01). On the other hands, mature‐BDNF was significantly augmented in MCAo+Jug compared to MCAo+Veh (p<.01). These results suggest that Pin1 isomerase is not only acts to accelerate an intrinsic apoptotic pathway but also interrupt to turn on the cell survival machinery after MCAo. Finally, Pin1 inhibition might alleviate the acceleration of apoptotic cell death that switch on the neuronal cell rescue signal after focal cerebral ischemic in rats.Support or Funding InformationFunding: NRF‐2012R1A1A2005089, NRF‐2013R1A2A2A01067169
Astrocytic Tissue Factor Plays An Important Role In Regulation Of CSF Circulation And Control Of Blood Spread Following Subarachnoid Hemorrhage
Authors: Golanov Eugene , Bovshik Evgueni , Foster Chase , Zhang Jonathan , Wong Kelvin , Wong Stephen , Britz Gavin 
Published: November 2023

Rupture of cerebral aneurysm leads to blood accumulation within the subarachnoid space, known as a subarachnoid hemorrhage. Fatality resulting from acute subarachnoid hemorrhage (SAH) reaches 50%. Volume of blood entering subarachnoid space (SS) following aneurism rupture is one of the leading factors determining the outcome. Retardation of cerebrospinal fluid (CSF) flow emerges as one of the key mechanisms limiting spread of blood in SS. It has been established that following SAH CSF flow is significantly reduced. We hypothesize that tissue factor (TF), the key factor of extrinsic pathway of coagulation cascade expressed by brain astrocytes, plays a critical role in reduction of CSF and localization of the hemorrhage following SAH.Perforation model of SAH was used in C57BL mice. We monitored changes of CSF flow by injecting fluorescent microspheres (0.02 um, FM) in cisterna magna (CM) from 1 hour to 30 days following SAH. We injected intracerebro ventricularly TF antibodies or IgG one hour before the perforation to explore role of TF in spread of blood across the SS and CSF flow.In naive and sham (no perforation) mice FM injected into CM filled ventral cisterns and spread along the perivascular space of Willis circle and middle cerebral arteries (MCA) reaching the olfactory bulbs within 1 hr. Following perforation of Willis circle, blood spread along the paravascular space, ventral cisterns and proximal trunk of ipsilateral MCA. FM injected into CM following SAH, were confined to the caudal ventral cisterns limited by the rostral pons border. CSF flow remained impeded for up to 30 days. The spread of hemorrhage did not correlate with the degree of CSF flow retardation. Block of TF by specific antibodies lead to significant (p<0.05) expansion of hemorrhage by 95%. In non‐SAH animals, intraventricular administration of TF antibodies significantly increased spread of CM injected FM compared to their spread following IgG administration (p<0.05). Subsequent immunohistochemistry demonstrated substantial association of TF with glia limitans, especially on the ventral brain surface.We conclude that TF plays an important role in localization of blood spread following arterial perforation. Moreover, block of TF by specific antibodies significantly facilitates spread of FM injected into CM allowing speculating that TF may play a regulatory role in CSF flow. It was suggested that astrocytes are the only source of TF in brain. We propose that astrocytes may exercise their CSF flow regulatory function and limit the blood spread through TF‐dependent mechanism.Support or Funding InformationOden Foundation
A Study of the Influence of Single Nucleotide Gene Polymorphisms on the Risk of Hypertension
Authors: Soliman Naglaa Raafat Abdraboh , Hemimi Neveen Salah 
Published: November 2023

BackgroundSeveral allele variants of human genes are proved to be linked with parthenogenesis of hypertension. The aim of this study is to identify the association of hypertension with single nucleotide polymorphism in four genes including, endothelial nitric oxide synthase (eNOS rs 1799983), angiotensinogen (AGT rs 699), lipoprotein lipase (LPL rs 320), and methyl tetrahydrofolate reductase (MTHFR rs 180113338, MTHFR rs 1801131 ).Material and MethodThe SNPs were genotyped in 180 hypertensive and 198 age and gender matched normotensive individuals using polymerase chain reaction‐ restriction fragment length polymorphism.ResultseNOS rs 1799983 and AGT rs 699 were found to be significantly associated with hypertension OR (95% CI) 2.7(1.27–5.60); and 2.3 (1.00–5.10) respectively, p<0.05. The other 3 SNPs have shown a tendency to increase the risk with OR between 1.5 and 2.2 with no statistical significance. The risk of hypertension was increased with simultaneous presence of risky alleles of eNOS rs 1799983 with other SNPs as MTHFR rs 1801131 OR 2.2 (0.70–2.69), AGT rs 699 OR 2.6 (0.3–22.99), LPL rs 320 OR 4.2 (1.88–9.41) and rs 180113338 OR 4.8 (1.19–19.27).ConclusionWe concluded that coincident appearance of some genetic alleles may increase the risk of hypertension and could be a predictive genetic profile for the disease.Support or Funding InformationThe research was funded by Dubai Medical College.
The role of conditional controlled photoperiodicity with propionic acid in induction of autism‐mimetic animal model during prenatal phase
Authors: Lee Seunghoon , Hong Yonggeun 
Published: November 2023

We determined whether prenatal pups were affected the brain and physiological development by exposure of propionic acid (PPA) as well as conditional photoperiods, which are could be modulate the secretion of endogenous melatonin secretion. Indirectly PPA‐treated rats were significantly increased body weight at 3‐ and 4‐week‐old after partus. All of PPA‐treated rats brain was organized the neuronal cell more than control groups following controlled photoperiodicity. All of experimental groups were not significantly altered organization of neural cells components. In behavioral test, constant dark condition (DD) revealed to delayed organization of neural architecture in cerebral cortex and hippocampus compared to constant light condition (LL). There were not significantly altered an exploring activity. Conversely, PPA+DD was similarly increased an inner square exploring activity but not in the PPA+LL group. We were not clearly defined for autism‐mimetic animal model induction during prenatal period via PPA exposure. Conditional controlled photoperiodicity might act on environmental stress for embryonic neural development in both control and PPA exposure. In future, we will process the embryonic stage for PPA exposure via placenta. Thus, we will clarify the effect of prenatal PPA exposure during pregnancy with conditional photoperiod.Support or Funding InformationFunding: NRF‐2012R1A1A2005089, NRF‐2013R1A2A2A01067169
Effects of endogenous melatonin regulated by conditional controlled photoperiodicity on neural reorganization through ER stress response and autophagy pathway after spinal cord injury
Authors: Jin Yunho , Hong Yonggeun 
Published: November 2023

Spinal cord injury (SCI) causes serious neurological deficits. The purpose of this study was to elucidate the effect of endogenous melatonin on neural reorganization and locomotor recovery through regulation of autophagy and endoplasmic reticulum (ER) stress response after SCI. To diversify the concentration of endogenous melatonin, subjected animals were divided into 5 groups; group1 (12‐hr light/12‐hr dark, L/D), group2 (6‐hr light/18‐hr dark, 6L/18D), group3 (24‐hr dark, DD), group4 (18‐hr light/6‐hr dark, 18L/6D), group5 (24‐hr light, LL). At 7 days after injury, locomotor test based on BBB (Basso, Beattie, Bresnahan) scale was conducted to identify functional recovery and the animals were sacrificed for further molecular and histological analyses. The rats under LL condition showed great recovery of motor function after SCI. Moreover, the expression of neuronal marker and autophagy marker was also upregulated in DD group. However, the protective role of ER stress response seems to be ambiguous. In conclusion, autophagy rather than ER stress response in SCI might play a critical role in neuroprotection, which is thought to be intensified by endogenous melatonin induced by conditional controlled photoperiodicity.Support or Funding InformationFunding : NRF‐2012R1A1A2005089, NRF‐2013R1A2A2A01067169
An Empirical Test of Metabolic Effects and Adaptive Potential in Response to Global Ocean Warming in a Model Fish Species, the Threespine Stickleback
Authors: Morozov Sergey , McCairns R.J. Scott , Leinonen Tuomas , Merilä Juha 
Published: November 2023

Climate change has had a significant influence on the world's oceans, which have shown constant increases in mean water temperature over the last 50 years. The biota of Arctic environments, ectotherms in particular, may be particularly threatened by this change: whilst southern animals have the possibility of migrating north, those adapted to colder northern climes have nowhere left to move and may be faced with the ‘choice’ of adapt or die. A key factor in adaptation to the changing thermal environment is the physiological response. Metabolic scope (the difference between minimum and maximum oxygen consumption rate) is likely a key fitness related trait because it defines energy available for locomotion, growth and reproduction. The unifying aim of our research is to develop a deeper understanding of the constraints and/or adaptive potential in metabolic scope with respect to thermal changes predicted due to climate change.As obligate ectotherms, threespine stickleback (Gasterosteus aculeatus) populations adapted to localized thermal conditions provide an excellent and logistically tractable model for study of thermal and metabolic evolution in a changing environment. We collected broodstock from anadromous Barents Sea fish and bred them under controlled conditions for two generations to standardize environmental & maternal sources of variance. The multi‐generational pedigree and large numbers of families (N=180, 40 families) permits estimation of additive genetic variance, whereas repeated measurements in multiple environments allows us to estimate direct environmental variance on metabolism and swimming performance. Maximum and minimum metabolic rates, in addition to critical swimming performance, were measured with the same individuals at three different temperatures: (i) contemporary summer temperature for Barents Sea coastal waters (12°C), (ii) extreme predictions under global warming (17°C), and (iii) stressful temperature (80% of CTmax). Individual critical temperature in observed population varied between 27.2 and 32.1°C. The preliminary results showed that minimum and maximum metabolic rates increased with the temperature rise: 61.6 ± 10.1 and 126.2 ± 36.1 mg O2/kg/hour at 12°C; 70.19 ± 11.8 and 144.9 ± 38.8 mg O2/kg/hour at 17°C; 114.0 ± 15.7 and 183.7 ± 32.0 mg O2/kg/hour at individual stressful temperature, respectively. However, the highest aerobic metabolic scope and swimming performance were observed at 17°C. Quantitative genetic analyses are ongoing, but point to the broad potential for adaptation to environmental change.Support or Funding InformationSM: Alfred Cordelin Foundation, Otto A. Malm Foundation, Oscar Öflund Foundation, LUOVA doctoral programme; RJSM, JM, TM: Academy of Finland
Hypermetric Tracheal Scaling as a Factor in Insect Gigantism
Authors: Wagner Julian , Duell Meghan , Harrison Jon 
Published: November 2023

Why are insects small? In the Paleozoic Era, atmospheric oxygen levels peaked significantly higher than the current level. Along with this oxygen peak came giant insects, many times larger than those currently observed. This suggests that oxygen transport may inhibit insects from becoming giants. If this were the case, then one would expect to observe an increase of investment in gas exchange structures in larger insects, i.e. hypermetric scaling. This has been observed in tenebrionid beetle trachea. In this study, we look at scarab beetles, since they have a large range of sizes including the largest extant insect species. Using sets of micro‐CT images of freshly dead scarabs taken at 180 degrees around the beetle, 3d reconstructions of the specimens were made. Using Aviso Fire, the eight spiracles, coxal‐trochantal areas, and the mesothoracic femoral tracheal volumes were measured. The spiracle areas showed isometric scaling with a slope of 0.70. However, spiracle area over spiracle depth showed a steeper slope in the proximal abdominal and thoracic spiracles as compared to the distal abdominal spiracles, suggesting that larger beetles may exhibit different dimensions in their spiracles to promote the spiracle's diffusive abilities (larger area compared to depth allows more air to flow a shorter distance via diffusion). The scaling of the area of the coxal‐trochantal trachea showed a larger slope than the scaling of the area of the coxa with a p value of 0.09 in a t test. The femur structure showed isometric scaling, whereas the femoral trachea showed hypermetry with a slope of 1.46, which differed from a slope of 1 with a p value of 0.0012 in a t test. These indicate that structures far from oxygen intake at the spiracles scale hypermetrically in scarabs.Support or Funding InformationThis research was supported in part by funds from the School of Life Sciences Undergraduate Research (SOLUR) Program through the School of Life Sciences at Arizona State University, Tempe Campus, and by NSF 1122157