bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased plasma levels of TGF‐beta1 and CD14+/CD105+ numbers in by‐pass patients correlate to increased CD105‐induced expression after plasma incubation
Authors: Tejerina Teresa , Navarro‐Dorado Jorge , Ramajo Marta , Gordillo‐Moscoso Antonio , Redondo Santiago , Carnero Manuel , Gonzalez‐Rocafort Alvaro , Alegria Victoria , Rodriguez Enrique , Reguillo Fernando 
Published: June 2021

ObjectiveCompare the numbers of CD14+/CD105+, plasma levels of TGF‐beta1, apoptosis and induced CD105 expression in atherosclerotic patients (bypass surgery) and control ones (valvular patients).MethodsBlood was taken from our patients and CD34+/CD144+, CD34+/KDR+ and CD14+/CD105+ cells were assessed by flow cytometry (R=0.8908). Plasma was added to peripheral blood mononuclear cells. CD105 expression was assessed by Western blot (day 4). Apoptosis was measured as DNA fragmentation (day 7).ResultsBy‐pass patients had a higher number of CD14+/CD105+ (5.357 vs 2.829% lymphocytes, p=0.04; 87.13 vs 49.77 cells/mcL, p=0.0339) and a higher level of plasmatic TGF‐beta1 (72.01 vs 48.33, p=0.0033). When plasma from by‐pass and valvular was added to cell (day 7), valvular plasma triggered apoptosis (0.9998 vs 1.599, p=0.0078), an effect mimicked when plasma from by‐pass was coincubated with the TGF‐beta1 blockers SIS3 (0.9998 vs 1.624, p=0.0034) and SB‐431542 (0.9998 vs 1.802, p=0.0108). In Western blot, a trend was found towards higher CD105 expression with plasma from bypass (0.94 vs. 0.57, p=0.18).ConclusionPlasma from by‐pass patients deregulates the effect of TGF‐beta1, which correlates to increased plasmatic TGF‐beta1 levels and CD14+/CD105+ cells and a trend towards higher in vitro expression of CD105.DisclosureFunded by FISS PI041018 (Spanish Ministry of Health).
Response‐Maintaining Effects of Quinpirole in the Rat: Effects of Operant History and Drug‐Paired Stimuli
Authors: Collins Gregory Thomas , Woods James Henry 
Published: June 2021

D2‐like agonists, such as quinpirole (QPRL), maintain responding in rats and monkeys, but are rarely abused in humans. These studies were aimed at examining the influence of operant history and drug‐paired stimuli on QPRL maintained responding in rats. Rats were trained to nosepoke (NP) on a FR1 for cocaine (COC) with a 5 s TO signaled by houselight illumination. Once responding stabilized, COC, QPRL, or saline (SAL) were substituted (SUB) with and without the COC‐paired stimuli, or on a previously inactive lever (LV). During LV SUBs, LV presses produced an injection followed by a 5 s TO signaled by a flashing houselight; NPs still produced the COC‐paired stimuli, but no injection. COC maintained stable responding regardless of whether stimuli were presented, whereas QPRL maintained responding only when the stimuli were paired with injection. During the LV SUB, responding was reallocated from the NP to the LV when COC was available, whereas NPs persisted, and LV presses were low when QPRL was available. These results suggest that the response‐maintaining effects of QPRL are primarily mediated by an enhancement of the conditioned reinforcing effects of the stimuli that were previously paired with COC.Supported by NIDA grants DA 020669 and F013771
Clock gene plays an important role in time‐dependent change in thermoregulation during cold exposure in fasted mice
Authors: Tokizawa Ken , Uchida Yuki , Nagashima Kei 
Published: June 2021

BACKGROUNDFood deprivation decreases body core temperature (Tb) in mice, which shows time‐dependency, greater in the inactive phase and smaller in the active phase. The purpose of the present study was to clarify the mechanism involved in the change of Tb rhythm during fasting.METHODSMale ICR wild‐type (WT) and Clock mutant (CM) mice were housed at 27°C in a 12:12‐h light‐dark cycle. After 48‐h fasting, ambient temperature was maintained at 20°C for each in the light phase (LP) or dark phase (DP). Tb, oxygen consumption, UCP1 mRNA level in the brown adipose tissues, and Fos‐IR cells in the hypothalamus were assessed.RESULTSTb decreased in the cold in all the groups. In WT, the reduction was greater in LP than in DP; however, the reduction was similar in both the phases in CM. Oxygen consumption and UCP1 mRNA increased in the cold in DP of WT and both the phases of CM, whereas remained unchanged in LP of WT. After cold exposure, counts of Fos‐IR cells increased in the medial preoptic area and paraventricular nucleus in all the groups, which were greater in DP of WT and both phases of CM than in LP of WT.CONCLUSIONThese results indicate that fasting attenuates thermoregulatory responses to the cold, depending on time of the day. Neuronal activities in the hypothalamus during the cold exposure may be associated with the thermoregulatory response and its time‐dependency, for which Clock gene plays an important role.
Beta‐GPA‐induced changes in mitochondrial biogenesis are associated with a muscle type‐dependent decrease in RIP140
Authors: Williams Deon , Basaraba Susan , Sutherland Lindsey , Bomhof Marc , Thrush Brianne , Dyck David , Field Catherine , Wright David 
Published: June 2021

Beta‐guanidopropionic acid (β‐GPA) is a creatine analogue that leads to reductions in ~P concentrations and increases in markers of mitochondrial content in rodent skeletal muscle. Prior evidence attributes these changes to activation of the 5'AMP pathway; however data suggest RIP140, a negative downstream regulator of PPAR gamma co‐activator 1 alpha (PGC‐1α), is a likely player in the regulation of mitochondrial biogenesis (MB). The aim of this study was to determine if β‐GPA feeding decreases RIP140 protein in skeletal muscle in a fiber type‐specific manner and if it is associated with an increase in mitochondrial content. Male Wistar rats were fed a semi‐purified diet supplemented with (n=12) or without (n=12) 1% β‐GPA for 6 weeks. β‐GPA feeding induced skeletal muscle MB in tricep as shown by increases in CORE1 and COXIV protein and citrate synthase activity. In contrast, no such changes were seen in soleus from β‐GPA‐fed rats. β‐GPA feeding led to a ~75% increase in PGC1α messenger RNA expression in tricep and ~140% increase in soleus. RIP140 protein decreased ~40% in tricep while it was unchanged in the soleus. In summary, β‐GPA feeding led to decreases in RIP140 in rat tricep only, correlating to increases in MB in only this muscle type. This suggests that RIP140 may play a key role in regulating MB downstream of PGC1α and provides a mechanism for fiber type differences in muscle adaptation.Supported by NSERC
Simvastatin represses eukaryotic initiation factor 2B (eIF2B) expression and activity in C2C12 myoblasts with concomitant reductions in protein synthesis
Authors: Tuckow Alexander P , Jefferson Sarah J , Kimball Scot R , Jefferson Leonard S 
Published: June 2021

Statins are a widely prescribed class of cholesterol lowering drugs whose use is frequently associated with muscle related ailments. A number of mechanisms have been implicated in statin‐induced myotoxicity including alterations in both protein synthesis and protein degradation. The objective of the current study was to explore the mechanism(s) contributing to the statin‐induced reduction in protein synthesis in a muscle‐derived cell line. C2C12 myoblasts were treated with 10 μM simvastatin or vehicle alone for 24 h in low serum conditions. Cells exposed to simvastatin exhibited reduced rates of protein synthesis as evidenced by [35S] methionine incorporation into protein. The reduction in protein synthesis occurred with a concomitant repression of the guanine nucleotide exchange activity of eIF2B, a regulated and rate‐controlling enzyme known to affect global rates of protein synthesis. Simvastatin treatment also resulted in reduced expression of several subunits of the eIF2B heteropentameric complex at the protein level without alterations in expression of the mRNAs encoding the respective subunits. Finally, increased phosphorylation of the catalytic epsilon subunit at Ser535 was observed ‐ an event consistent with reduced eIF2B activity. These results suggest that repression of eIF2B expression and activity may contribute, at least in part, to the statin‐induced reduction in protein synthesis.Supported by grant DK15658
Regulation of Transcription of Renal Proximal Tubule Na,K‐ATPase by G‐Protein Coupled Receptors
Authors: Taub Mary , Springate James E , Khrovi Sudha 
Published: June 2021

Our previous studies indicate that transcription of the Na,K‐ATPase beta subunit gene in MDCK cells is regulated by Prostaglandins, via 2 Prostaglandin Regulatory Elements (PGREs). In order to determine whether 1) our studies with MDCK have a broader physiologic significance, and 2) similar regulation occurs in the renal proximal tubule (RPT), transient transfection studies were conducted with primary rabbit RPT cells. When transfecting using pH ?1‐1141Luc, a beta subunit promoter/luciferase construct, we observed a stimulation by PGE1 and PGE2 , as well as the Gs‐coupled EP2 and EP4 receptor agonists butaprost and PGE1‐OH (respectively). The PGE1 stimulation was inhibited by the antagonists SC51089 and AH6909 (which block Gq coupled EP1 receptors).Na,K‐ATPase in the renal proximal tubule is regulated by epinephrine and dopamine, which, like PGE, act via G‐ Protein Coupled Receptors (GPCRs). Indeed, 1 µM epinephrine stimulated transcription, as well as the alpha 1 and beta agonists phenylephrine and isoprenaline, respectively. Similarly, dopamine was stimulatory, an effect which was inhibited both by the D1 and D2 receptor antagonists, SCH23390 and L741, 626, respectively. These results are consistent with previously reported chronic stimulatory effects of dopamine on renal Na,K‐ATPase (in addition to acute inhibition), and may be mediated transcriptionally via PGREs.
Urocortin 3 Microinjected Into The Intermediolateral Cell Column Elicits Tachycardia In The Rat
Authors: Chitravanshi Vineet C , Sapru Hreday N 
Published: June 2021

Urocortin 3 (Ucn 3) is a new member of corticotropin releasing factor (CRF) family of peptides. There is limited information about the cardiovascular actions of this peptide. Urethane‐anesthetized, artificially ventilated, adult male Wistar rats, weighing between 325‐350 gm, were used in this study. L‐Glutamate (L‐Glu; 5 mM), microinjected (30 nl) into the right intermediolateral cell column (IML) at T1 or T2 level, elicited an increase (35 ± 4 bpm) in heart rate (HR). The onset and duration of these responses was 5 and 50‐60 sec, respectively. Microinjections (30 nl) of Ucn 3 (0.31, 0.62, 0.12 and 0.25 mM) into the same sites in the IML elicited tachycardia; the increases in HR were 13.6 ± 1.5, 31.8 ± 3.9, 37.9 ± 2.1 bpm and 33.6 ± 3.4 bpm, respectively. Maximum tachycardic responses were elicited by 0.12 mM concentration of Ucn 3. The tachycardic responses elicited by Ucn 3 (0.12 mM) were significantly attenuated by prior microinjections (30 nl) of a selective antagonist (K41498, 1 mM) for CRF type 2 receptors. It was concluded that Ucn 3 exerts an excitatory effect on IML neurons controlling cardiac function.Support: NIH grants HL024347 and HL076248.
Protective effect of hypothermia and mannitol postconditioning on mouse brain suffered from ischemic/reperfusion injury
Authors: SHEN Jia , LI Menghan , BAI Xiaoyin , XIA Qiang 
Published: June 2021

OBJECTIVEThe aim of the study was to determine the synergistic protective effect of mild hypothermia combined mannitol therapy against global cerebral ischemia/reperfusion (I/R) injury and the underlying mechanisms.METHODSMale C57BL/6 mice (22‐28g) were randomly divided into sham group (Gourp S), control (ischemia/reperfusion) group (Group C), mild hypothermia (31‐33°C, 2h after reperfusion) group (Group Ht), mannitol (20% mannitol, caudal intravenous infusion) group (Group Ma), mild hypothermy combined mannitol group (Group Ht+Ma). Learning and memory abilities were detected by Morris water maze task, the CA1 region neuron survival rates were detected by Nissl staining, the activities of superoxide dismutase (SOD) of hippocampus tissue were measured.RESULTSThe average escape latency and swimming distance of Group Ht+Ma were significantly shorter than Group C, also shorter than those of Group Ht and Group Ma. The average neuron survival rates were markedly increased in Group Ht+Ma, Group Ht and Group Ma, more than that in Group C. The SOD activity of Group Ht+Ma was remarkably higher than control group, and higher than group Ht and group Ma.CONCLUSIONThe therapies of mild hypothermia and mannitol have protective effect against global ischemia/reperfusion injury. The combination of mild hypothermia and mannitol therapy enhances the protection effect by increasing the SOD activity.
High altitude acclimatization responses in cerebral artery PKC‐dependent signaling pathway proteins: Changes with development
Authors: Goyal Ravi , Mittal Ashwani , Shi Lijun , Wedhas Nia , Longo Lawrence D. 
Published: June 2021

ObjectiveHigh altitude, long‐term hypoxia (LTH) is associated with a number of changes in pre‐ and post‐junctional signaling in both fetal and adult cerebrovasculature. Because PKC and downstream pathways play a key role in Ca2+ sensitization of vascular contraction, and are less abundant in fetus, we tested the hypothesis that LTH alters PKC activation pathways differently in the fetus, as compared to the adult.MethodsIn cerebral arteries we quantified both total and activated (phosphorylated) PKC, ERK1/2, caldesmon, Rho A, CPI‐17, and myosin light chain20 (MLC20), and PDBu‐ (PKC agonist) induced contractions and their responses to blockade of ERKs (U‐0126) or Rho kinase (Y‐27632).ResultsIn adult cerebral arteries, LTH acclimatization was associated with significant decreases in total and activated PKC, with increases in activated ERK1/2, CPI‐17, and MLC20 and its kinase. In contrast, in fetal arteries LTH increased PKC expression and increased ERK1/2 activation, with no change in caldesmon, Rho A, CPI‐17, or MLC20.ConclusionsIn adult cerebral arteries, acclimatization to LTH is associated with significant up‐ or down‐regulation of a number of elements of the PKC‐dependent Ca2+ sensitization pathway. In contrast, acclimatization to LTH in the fetus is associated with relatively minor changes in the Ca2+ sensitization pathway. (Supported by USPHS HD 31226)
The effect of life‐long caloric restriction on alpha motoneuron numbers in aged rats
Authors: Chopek Jeremy William , Gardiner Phillip 
Published: June 2021

The objective of this study was to determine if caloric restriction (CR) attenuates the age‐related loss of alpha‐motoneurons (α‐mns). Rats were either fed ad libitum (oldAL) or a fortified CR (40% reduction) diet from 14 weeks of age (oldCR). A control group of young free eating rats (youngAL) was also studied. Rat lumbar enlargements were sectioned at 15 μm and every sixth section for 3mm was used for immunohistochemistry. Choline acetyltransferase (ChAT) ‐ positive neurons in the ventrolateral horn larger than 15 micrometers ( μm) in diameter and each having a clear soma and nucleus were sized and counted. Results demonstrated a significant age effect (p < 0.05) on the total number of α‐mns (diameter = 25 μm). A decrease of 28% in α‐mn numbers was found in the old (31 months) rats compared to the young (8.5 months) rats. No age effect was evident on the total number of gamma‐mns (diameter < 25 μm). While CR attenuated the loss of muscle mass with age, there was no effect on age‐related mn loss since there was no difference between the total number of alpha or gamma mns between the oldCR and oldAL rats. Caloric restriction, while attenuating age‐associated changes in muscle mass and brain apoptosis markers, does not attenuate the decline in mn numbers in the rat lumbar spinal cord.Supported by funds from CIHR and MHRC
Angiotensin 1‐7 treatment induces apoptosis in Human Umbilical Vein Endothelial Cells.
Authors: Anene‐Maidoh Ogugua T. , Greene Andrew S. 
Published: June 2021

Angiotensin 1‐7 (ANG1‐7), a physiologically active product of the Renin‐Angiotensin system, plays an important role in the regulation of the cardiovascular system. Acting through the Mas receptor, ANG1‐7 counter‐regulates the actions of Angiotensin II (ANGII) mediated by AT1. ANGII is protective in certain cell types but induces apoptosis in human umbilical vein endothelial cells (HUVECs). We therefore hypothesized that ANG1‐7 would have proliferative effects on HUVECs.HUVECs were incubated for 24 hours in M199 media, treated with ANG1‐7 (0.1nM ‐ 10uM) in serum free media for 24 hours, and then allowed to recover for 3 hours in M199 media. A cell viability assay was performed. Compared to control cells left in complete media for the duration of the experiment, all serum starved cells showed a significant decrease in cell number. ANG1‐7 caused a further decrease in cell number compared to serum starved non‐treated controls. These data suggest that ANG1‐7 treatment does not rescue HUVECs during serum starvation but instead stimulates the increased induction of apoptotic pathways. These experiments demonstrate a dose dependent and cell type specific action of ANG1‐7 that can either augment or counter the effects of ANGII. Support NIH HL 29587
Interstitial nitric oxide levels do not increase following L‐Arginine or ATP perfusion into the interstitium of rat hind‐limb skeletal muscle
Authors: Smith Ashley A. , Zhao Yi , Fabris Sergio , MacLean David A. 
Published: June 2021

It has been proposed that increased extracellular L‐Arginine (L‐Arg) or ATP stimulates nitric oxide synthase activity producing nitric oxide (NO). In the present study we used the microdialysis technique to alter the interstitial concentration of L‐Arg and ATP to examine whether elevations in these compounds results in nitric oxide formation in rat skeletal muscle. Male Sprague‐Dawley rats were anaesthetized and had microdialysis fibers (1 cm diffusion length) inserted into the gastrocnemius muscle of each leg. Following 20 min. of baseline collection (saline), the microdialysis probes were perfused at a rate of 5 uL/min with either 20 mM L‐Arg (20 min., n = 10) or 60 uM ATP (20 min., n = 15). Interstitial NO concentrations were 7.2±1.1 and 5.2±0.7 uM during saline perfusion and did not change (P>0.05) following L‐Arg (6.5± 0.8 uM) or ATP (5.6±0.9 uM) perfusion. These data clearly demonstrate that elevated interstitial L‐Arg as well as ATP concentrations did not alter the basal interstitial concentrations of NO. Furthermore, these data suggest that the independent manipulation of L‐Arg and ATP in the interstitial space alone does not promote NO production and release from surrounding tissues.Supported by NSERC.
APS Undergraduate Summer Research Fellowship program: exposing undergraduates to physiology research leads to a research‐focused career
Authors: Lowy Melinda E. , McHugh Nansie A. , Galey William R. , Matyas Marsha Lakes 
Published: June 2021

The APS Undergraduate Summer Research Fellowship (UGSRF) program seeks to excite and encourage undergraduate (UG) students worldwide to pursue a career as a basic research scientist. The program has 5 objectives: develop a research project, collect/analyze data, write up results; give a presentation on results at a scientific meeting; attend a national meeting; commit to a research career; and enroll in a graduate/professional program in basic biomedical research.Since the UGRSF program began in 2000, 109 undergraduates have participated. Most students (92%) attended EB meeting and made 99 presentations, with some students having more than one abstract or presentation. Over 35% of the students published a paper on their APS‐funded research.From surveys 2 years post‐Fellowship, 85% of the UGSRFs had graduated. Of these, 46% applied to graduate school (PhD or Master's programs) and 74% were accepted. As well, 58% applied to a science‐related professional school (MD, etc.) and 75% were accepted. At the time of the survey, most (78%) were already enrolled in a graduate or professional degree program.In 2007 and 2008, the program added an online interactive component where UGSRFs discussed professional networking, structure of research studies, and career options in biomedicine. Results indicated the online interaction provided a powerful tool for UG students to explore critical professional development topics.
Cardiac Birth Defects Caused by Lifestyle and Their Potential Prevention by Nutritional Molecules
Authors: Memon Samreen , Pratten Margaret Kathryn 
Published: June 2021

Heart defects are responsible for many neonatal deaths. Changing life styles, (exposure to retinoic acid, excessive alcohol or nicotine) could be a cause of congenital malformations. Supplementation with vitamins during the periconceptional period has been shown to prevent neural tube defects. In this study embryonic hearts were dissected from 5 day old White Leghorn chick embryos and the isolated cells cultured in DMEM medium. The cells were exposed to 100µl/ml ethanol or 10µM nicotine only, or with the addition of 100µM vitamin C. Similarly, cells were exposed to 10µM retinoic acid, or retinoic acid plus 1mM folic acid. Cultures were incubated at 37oC in 5% CO2 in air, and observations made for cardiomyocyte differentiation at 24, 48, and 144 hours, cell viability assessed using the resazurin reduction assay and cell number by the kenacid blue assay. Statistical analyses were via ANOVA and Kruskal Wallis tests. Ethanol and retinoic acid dramatically reduced differentiation, viability and protein content (p <0.01). Vitamin C administered concurrently with ethanol, or folic acid with retinoic acid, could significantly improve all parameters to those comparable with the control. Nicotine only had an effect on the rate of beating, this being reversed by the addition of Vitamin C. It may be that environmentally induced teratogenic effects could be prevented by vitamin supplementation during pregnancy.Funded by Government of Pakistan
Analyses of the craniofacial skeleton of a zebrafish lens degeneration mutant
Authors: Franz‐Odendaal Tamara Anne 
Published: June 2021

The zebrafish mutant, bumper, is characterized as having a lens defect, which begins at 4dpf. Previous work has shown that in the blind morph of Astyanax mexicanus, which also has a lens defect, the ocular skeleton is affected. The ocular skeleton of sighted Astyanax mexicanus and wildtype Danio rerio consists of two scleral ossicles joined by scleral cartilage. In the blind tetra morph, however, the scleral cartilage is persistent and is not replaced by bone. In this study, homozygous and heterozygous bumper mutants of Danio rerio were analyzed. Whole‐mount analyses show that the ocular skeleton is unaffected in this mutant, unlike in blind tetras. Surprisingly, however, several other regions of the craniofacial skeleton are affected; these include the jaws and skull vault. The significance of these results is discussed with respect to the nature and timing of eye degeneration in the two species analyzed. Funding: NSERC, CanadaGrant Funding SourceNSERC, Canada