bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired fasting blood glucose‐related exacerbation of age‐associated vascular endothelial dysfunction: protective effect of regular aerobic exercise
Authors: DeVan Allison E. , Eskurza Iratxe , Pierce Gary L. , Walker Ashley E. , Jablonski Kristen L. , Kaplon Rachelle E. , Seals Douglas R. 
Published: June 2021

We tested the hypothesis that impaired fasting blood glucose (IFG) exacerbates vascular endothelial dysfunction with aging, and that this effect is smaller or prevented by habitual exercise. Brachial artery flow‐mediated (endothelium‐dependent) dilation (FMD) was lower (5.14±0.38 vs. 8.06±0.35 %Δ, P<0.001) in older adults with normal fasting blood glucose (NFG, ≤99 mg/dl, 62±1 yrs, n=37, 31M/6F) vs. young NFG controls (24±1, n=29, 26/3). FMD was further impaired (3.62±0.38 %Δ, P<0.01 vs. older NFG) in otherwise healthy older adults with IFG (100–125 mg/dl, 64±1, n=31, 26/5). Older adults with NFG who regularly (≥3d/w) performed moderate to vigorous aerobic exercise (62±1, n=23, 21/2) had largely preserved FMD (6.38±0.35 %Δ, P<0.05 vs. older NFG). Most importantly, FMD also was well preserved (7.02±0.65 %Δ) in older exercising adults with IFG (65±1, n=17, 13/4). These overall group differences remained significant (P<0.05) after controlling for endothelium‐independent dilation and clinical characteristics. In the pooled sample (n=137), FMD was inversely related to FG (r=−0.32, P<0.001), plasma insulin (r=−0.23, P<0.05) and an index of insulin resistance, HOMA‐IR (r=−0.28, P<0.01). IFG, a prediabetic state, exacerbates age‐associated vascular endothelial dysfunction. This adverse effect is prevented by regular aerobic exercise.NIH AG013038, AG000279, AG031617, AG033994, AG027910, RR025780
Mineralocorticoid Receptors Activation in Choroid Plexus and PVN Exaggerates Salt‐Induced Development of Hypertension in Stroke‐Prone Spontaneously Hypertensive Rats
Authors: Nakano Masatsugu , Hirooka Yoshitaka , Matsukawa Ryuichi , Ito Koji , Sunagawa Kenji 
Published: June 2021

BackgroundIn salt sensitive models, the increases in cerebrospinal fluid Na+ concentration (CSF [Na]) derived from choroid plexus (CP) play a pivotal role in high salt (HS) induced hypertension. Mineralocorticoid receptors (MR) contribute to Na+ handling. Therefore, we investigated whether MR in CP and paraventricular nucleus of hypothalamus (PVN) exaggerates salt‐induced development of hypertension in stroke‐prone spontaneously hypertensive rats (SHRSP).Methods and ResultsSerum glucocorticoid inducible kinase 1 (sgk1) expression levels in CP and PVN were greater in SHRSP than those in Wistar‐Kyoto (WKY) rats (N=6, P<0.05) associated with increases in CSF[Na] (155.6 ± 0.81 vs. 152.8 ± 0.49 mM, P<0.01). The depressor response to intracerebroventricular (ICV) infusion of MR blocker, eplerenone (10 ng) was greater in SHRSP than in WKY (Δarterial pressure (AP) −25.2 ± 1.4 vs. −8.2 ± 1.4 mmHg, N=5, P<0.001). In SHRSP, HS intake (8%) increased AP and urinary norepinephrine excretion (uNE) compared with those by regular salt diet (2 weeks after ΔAP 41.7 ± 3.2 mmHg, ΔuNE 0.24 ± 0.07 μg/day, N=5, P<0.05) associated with increases in MR and sgk1 expression in CP and PVN. These alterations were attenuated by ICV infusion of eplerenone (10 μg/kg/day).ConclusionMR activation in CP might contribute to increases in CSF[Na], thereby exaggerates salt‐induced development of hypertension via MR activation in PVN in SHRSP.
Enhanced endothelin‐1 response in mesenteric arteries in acquired and inherited forms of hypertension
Authors: Pulgar Victor M , Jeffers Anne B , Diz Debra I , Aileru Azeez A 
Published: June 2021

Both endothelin and the ET‐1 receptor are altered in ouabain sensitive and hypertensive (mRen‐2)27 transgenic rats, consistent with the lowering of blood pressure in both models of hypertension with either AT1 or ET‐1 receptor blockade. We hypothesized that responses to ET‐1 receptor activation are enhanced in the vasculature of the animals with acquired and genetic hypertension. Sprague‐Dawley rats were implanted subcutaneously with a 60‐ day 1.5 mg ouabain (OUA) pellet (n = 6 control, n = 6 treated). Blood pressure (BP) was recorded daily via tail cuff for 8 weeks. Transgenic hypertensive (mRen‐2)27 rats (n = 6) were also used. Third branch mesenteric arteries were mounted in a wire myograph (DMT‐USA). Maximal responses to KCl and ET‐1 were expressed as KMAX (mN/mm) and ET‐1MAX (% KMAX) and sensitivity as pD2 (pD2=‐Log[EC50]). Pre‐incubation with indomethacin (10−5M) or LNAME (10−4M) were performed in parallel. OUA increased systolic BP by 30% (p<0.05) whereas age‐matched (mRen‐2)27 rats had a 55% higher BP vs control (p<0.05). ET‐1MAX was similar in the three groups [ET‐1MAX (mRen‐2)27 136 ± 5%; OUA 128 ± 14% vs control 137 ± 8 % KMAX]. However sensitivity to ET‐1 was increased in hypertensive vs control rat vasculature [(mRen‐2)27 8.6 ± 0.1; OUA 8.5 ± 0.2 vs control 8 ± 0.1, p<0.05]. A greater sensitivity to ET‐1 may serve as mediator of enhanced vascular tone in both models of hypertension.Supported by NIMHD MD002303
RNAi Silencing of TNFα Attenuates Cold‐induced Pulmonary Hypertension (CIPH)
Authors: Crosswhite Patrick , Sun Zhongjie 
Published: June 2021

BackgroundExposure to a moderate cold temperature (5ºC) causes pulmonary hypertension. Tumor necrosis factor‐alpha (TNF‐α) was increased in lungs and pulmonary arteries of rats prior to cold‐induced elevation of pulmonary arterial blood pressure (PABP). The purpose of this study was to investigate if the upregulation of TNFα plays a role in CIPH.Methods and ResultsThree groups of male SD rats (8 rats/group) received IV delivery of adeno‐associated virus (AAV)‐carrying TNFα small hairpin RNA (TNFαshRNA), AAV‐carrying scrambled shRNA, and PBS, respectively, 3 days before exposure to a cold environment (5°C). Three additional groups with the same treatments were housed in a warm chamber (25°C) and serve as controls. Eight weeks after injection, right ventricular (RV) systolic BP (equivalent of PABP) was recorded and PA smooth muscle cells were isolated for in vitro studies. TNFαshRNA significantly decreased cold‐induced elevation of RV BP but not RV hypertrophy. TNFαshRNA prevented cold‐induced upregulation of TNFα in lungs and PAs, confirming effective silencing of TNFα. TNFα inhibition decreased cold‐induced increases in intracellular levels of O2−, calcium, and cGMP in PA SMCs. RNAi silencing of TNFα also prevented the cold‐induced increase in PCNA, a marker of cell proliferation.ConclusionsThe upregulation of TNFα may play a key role in the development of CIPH and PASMC proliferation.
New Opportunities and Challenges in Network Biology
Authors: Ideker Trey 
Published: June 2021

The past decade has seen an explosion in “genome‐era” technologies which profile genes, proteins, metabolites and the intricate web of interconnections among them. Much of bioinformatics and functional genomics is now focused on methods to assemble these diverse measurements into models of functional networks and pathways within the cell.

Mapping the genetic network underlying the response to DNA damage. We will describe our ongoing efforts to apply ChIP‐sequencing and synthetic‐lethal screens to map how the cellˈs transcriptional network is remodeled by DNA‐damaging conditions.
Network‐based biomarkers for disease diagnosis and personalized medicine. Recently, we have shown that networks can also serve as powerful biomarkers and in many cases are more predictive than any individual gene. Our approach is to project gene and/or protein expression profiles of each patient onto the known human genetic network map to identify pathways that are predictive of disease.
Protein network comparative genomics. We are developing a library of standard approaches for comparing protein interaction networks across species, conditions, and network types.
We are developers of the Cytoscape platform, an Open‐Source software environment for visualization and analysis of biological networks and models (http://www.cytoscape.org/).
Central melatonin modulates the ventilatory response to hypercapnia but not to hypoxia in anaesthetized rats
Authors: Sanchez Adriana Paula , Delchiaro Adriele , Giácomo João Francisco G , Pupin Juliana P , Luzzi Mayara C 
Published: June 2021

In the present study we assessed the participation of melatonin on ventilatory responses to hypercapnia and to hypoxia. To this end the pulmonary ventilation and body temperature of male Wistar rats was measured after microinjecting melatonin (0,5 mg/mL) or vehicle (DMSO) into the fourth ventricle followed by 60 min of hypercapnia (7% CO2) or hypoxia exposure (7% O2). Compared to the vehicle group, the ventilatory response to hypercapnia increased significantly (about 40%) in animals injected with melatonin by elevating respiratory frequency, however no effect was observed on ventilatory response to hypoxia. No difference in body temperature between groups was observed during hypercapnia or hypoxia. These data suggest that melatonin exerts an excitatory modulation on hyperventilation induced by hypercapnia but play no role on hypoxia‐induced hyperventilation.Financial Support: FAPESP, FIPA.
Tissue tension supports the in vitro co‐culture of ras‐keratinocytes and myofibroblasts
Authors: Barua Prognanwita , Lam Christina C. , Vaughan Melville B. 
Published: June 2021

Tissue tension is necessary to support the myofibroblast, a cell derived from a fibroblast and present in wound healing and tumor stromas. Currently‐used skin equivalent models lack the ability to generate tension. Our goal was to determine whether a tension‐maintaining skin equivalent model supports myofibroblast growth and the growth of ras‐keratinocytes, precancerous cells previously shown to modulate their phenotype in response to their environment. We developed a dermal equivalent with a plastic ring within a liquid collagen/fibroblast mixture and converted it to a skin equivalent by overlaying with keratinocytes. Skin equivalents were cultured at the air/liquid interface. Replicate tissues were harvested weekly and prepared for immunofluorescence staining. Myofibroblasts in the dermis were identified by alpha‐sm actin staining in stress fibers; ras‐keratinocytes differentiated and stratified atop the dermal compartment. Proliferation of both cell types was identified by EdU incorporation and staining. Interestingly, the keratinocyte strata consisted of disorganized clumps of cells rather than organized layers even though invasion into the dermal compartment was inhibited. The tension‐maintaining skin equivalent supports ras‐keratinocytes and can be used to study the role of myofibroblasts during cancer progression in vitro.Grant Funding Source : The University of Central Oklahoma and Grant Number P20RR016478 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH).
Growth change in cartilaginous Eustachian tube angulation and its relationship with age at onset of otitis media
Authors: Pagano Anthony Santino , Wang Eugene , Laitman Jeffrey T. 
Published: June 2021

Middle ear infection (otitis media, OM) is amongst the most common childhood diseases in the United States. Despite this, there is a lack of data on growth of the Carilaginous Eustachian tube (CET) and how this may relate to onset of OM. This study investigated growth changes in reconstructed CET dimensions. Its length (between its orifice on the temporal bone and medial pterygoid tubercle) and orientation (angle made with the medial pterygoid plate posterior edge) were quantified in a dry cranial growth series (n=258) divided into dental eruption stages. 3D landmark coordinate data were digitized from each specimen using a Microscribe digitizer. A total of 54 landmarks on the face, upper respiratory tract, and temporal bone were used. These data underwent Procrustes scaling so that relative dimensions could be directly compared between growth stages with Bonferroni‐adjusted T‐tests. Results showed no significant growth change in relative CET length but CET angulation underwent marked and significant (p<0.05) growth change between infancy and adulthood with greatest amount of change occurring within the first three years of life, coinciding with peak onset age for OM. The results suggest that the development of OM may be related to CET angulation and absolute length.Grant Funding Source : Mount Sinai School of Medicine
Changes in adult fibroblast populations with passaging reduce reprogramming efficiency
Authors: Su Elaine Jean , Downing Timothy , Li Song 
Published: June 2021

Induced pluripotent stem cell (iPSC) technology has immense therapeutic potential to treat injury and a variety of degenerative diseases. Previous research has suggested an elite model for the reprogramming of adult fibroblasts into iPSCs; in this model, a rare existing population of primary cells preferentially reprogram to pluripotency. While it is postulated that this elite population of cells could have adult stem cell origins, few studies have been able to identify the key attributes of such populations. Here, we explore the “reprogrammability” of a new adult stem cell population and study how changes in these cells over time (i.e. higher passages) undergo phenotypic changes that may contribute to decreased reprogramming efficiency. Preliminary results indicate a significantly higher reprogramming efficiency in lower passage cells; these data suggest that population changes and perhaps differentiation of progenitor cells in higher passages result in decreased number of “elite”, reprogrammable cells. This model is important for evaluating reprogramming mechanisms as well as for culture techniques for future clinical applications.Grant Funding Source: CIRM
Umbilical cord matrix stem cells trophic ability and use as a drug delivery vehicle for treatment of melanomas
Authors: Davis Kelsey M. 
Published: June 2021

Melanoma is caused by uncontrolled growth of melanocytes, which can lead to a progressive form of malignant melanoma with limited treatment options. Stem cells have previously demonstrated a trophic ability to melanoma, which could be used as an anti‐cancer delivery system. Interferon‐β (IFN‐β) has been used as an anti‐cancer drug in previous studies. Our aim was to use umbilical cord matrix stem cells (UCMSC) loaded with IFN‐β (UCMSC‐IFN‐β) as drug delivery vehicles for melanoma treatment. To investigate the trophic ability of UCMSC towards B16F10 melanoma cells, we plated B16F10 melanoma cells at increasing concentrations in the bottom of a transwell plate and UCMSC's plated in the top of transwells. After 24 hours, the number of UCMSC's showing trophic ability was counted. All the experiments were replicated three times. To investigate the anti‐cancer ability of UCMSC‐IFN‐β on B16F10 melanoma cells, we plated B16F10 melanoma cells at increasing concentrations in the bottom of a transwell plate. UCMSC and UCMSC‐IFN‐β were then plated in the top of the transwells. After 48 hours, the number of B16F10 melanoma cells both alive and dead was counted. All the experiments were replicated three times. This in vitro study shows that as melanoma cells concentration increased, the amount of UCMSC migration increased as well. The second study showed that wells with UCMSC‐IFN‐β had higher amounts of dead B16F10 melanoma cells as compared to the control wells with UCMSC. These results indicate the trophic ability of UCMSC's and the use as a drug delivery vehicle through the anti‐cancer ability of UCMSC‐IFN‐β.Grant Funding Source : A.T. Still University Graduate Program
Labeling of Porcine Mesenchymal Stem Cells (MSCs) with MRI contrast agent Ferex for use in Abdominal Aortic Aneurysm (AAA) Models
Authors: Faries Peter , Rawal Bhakti , Saeboe Karen Briley 
Published: June 2021

IntroductionReliable methods of labeling and tracking MSCs are necessary to allow non‐invasive evaluation of their effects on aneurysm. Ferex is a super paramagnetic iron compound that when placed intracellularly, can be identified by magnetic resonance imaging (MRI). This study aims to evaluate Ferex as an in vivo cellular label in Porcine AAA models.MethodsMSCs were isolated from the pig's bone marrow via ficoll plaque separation and expanded in culture. MSCs were incubated with 100ug/ml conc. of Ferex and a cationic transfecting agent, Poly‐L‐Lysine (PLL). Around 10 million Ferex labeled MSCs were then transplanted to the pig after a surgery that induced AAA. MRI was performed at 3 Tesla three times over a two week time period post surgery at day 4, 7 and 14 respectively. A longitudinal survey scan was performed to locate the AAA within the tissue. Time‐of‐Flight (TOF) and T2 weighted images were obtained to evaluate the vasculature and flow with in the AAA as well as to identify the iron laden cells within the arterial wall. Following the T2‐weighted scan, T2*‐weighted multiple echo gradient echo sequences were applied in order to quantify the signal on a pixel‐by‐pixel basis.ResultsAs shown in Figure 1, the iron labeled cells were visible (as signal loss) at all time points post transplant. T2* values strongly indicate that the iron cores remained within the labeled stem cells (and were not exocytosed and/or phagocytosed by other cells). The percent relative change in the normal arterial wall was 0.8 +/− 2%, respectively for all time points tested. Figure 2 summarizes the results obtained from the Perl's’ staining. Strong correlation between the in vivo MR signal and iron deposition (blue color on Perl's) was observed.ConclusionThe results clearly support the hypothesis and show that it is possible to detect iron over a two week time interval post transplant accompanied by strong correlation between MR and histology.
Superfast Electrophoretic Transport of Carbocyanine Dyes In Situ: An Improved Method in Nerve Pathway Tracing
Authors: Heuer Tiffany A , McMaster Brian , Hong Se-Pyo , Henderson Charles 
Published: June 2021

Carbocyanine dyes are an important tool used to trace the innervations to specific structures, and although the rate of dye transport has improved, faster rates are required to make these dyes effective especially in fixed tissues. We applied a direct electrical current to the sciatic nerve of a cat to electrophoretically transport pastes of DiI and DiD in situ, using a sodium borate (SB) buffer ‐ filled anode apparatus and hypodermic needle as a cathode. Dye labeling was visualized using a Bio‐Rad Radience 2100MP confocal microscope. DiI was transported at an average rate of 60.2 ± 4.1 mm/hr, which was >5,000 X faster than previously reported for crystal diffusion (Lukas et al. 1998, Swift et al. 2005) and 50 X faster than using a DC field in vitro. The average electrophoretic transport rate of DiD (60.9 ± 7.0 mm/hr) was similar to DiI. Lower crystal solubility and reverse micelle formation may be responsible for the slower diffusion rates reported previously. Use of the paste form with a lower alcohol content together with SB buffer solution, could reduce reverse micelle formation, and improve diffusion. Initial counter‐ion distribution at the anode may facilitate development of superfast electrophoresis in a weak field (5mA). This could allow the small ions to facilitate superfast electrophoretic transport of the carbocyanine dyes at low currents.Grant Funding Source : Palmer College of Chiropractic
HIF‐1alpha and COX‐2 expression and mouse brain capillary remodeling during adaptation to hypoxia and re‐oxygenation after prolonged moderate hypoxia
Authors: Benderro Girriso , LaManna Joseph Charles 
Published: June 2021

Normal brain function is delicately sensitive to continuous and controlled oxygen delivery. One of the ways that the brain maintains its optimal continuous supply of oxygen and nutrients is through brain angiogenic adaptational changes. Hence, the objective of this study was to determine the relative time course of the capillary regression during re‐oxygenation after chronic hypoxic exposure, and expression of some of the signaling factors involved in the process. Four month old male C57BL/6 mice were kept in a hypobaric chamber at 290 torr (0.4 ATM) for 21 days and allowed to recover at normoxia for up to 21 days. The mice were either decapitated or perfused in situ and brain samples collected were either lysated for Western blot analysis or paraffin embedded for immunohistochemistry. Hypoxia inducible factor 1alpha (HIF‐1á) accumulation in hypoxia was observed to be diminished during re‐oxygenation; however, Cyclooxygenase‐2 (COX‐2) expression was elevated during hypoxia as well as re‐oxygenation. Significantly increased capillary density at the end of the 3rd week of hypoxia regressed toward normoxic level as the duration of re‐oxygenation was prolonged. In conclusion, increased COX‐2 expression during hypoxia where angiogenesis occurs and re‐oxygenation, when micro‐vessels regress indicates the involvement of this enzyme in wide range of brain angioplasticity.Grant Funding Source : NS38632
Embryonic origin of microglial progenitors and their routes of entry into the mouse developing central nervous system
Authors: Chan Wood Yee , Ng Tsz Chung , Chow George W.H. , Rezaie Payam 
Published: June 2021

Mircoglia are specialized mononuclear phagocytes within the central nervous system (CNS). Their embryonic origins and routes of entry to the CNS remain controversial. In this study, we used Iba1 as a specific marker for microglial progenitors in mouse embryos and employed multiple immunohistochemical localization and tissue transplantation to establish (1) their routes of entry to the CNS and (2) their origin. Iba1+ microglial progenitors were found in the mesenchyme at E9.5, and started to appear in the neural tube at E10.5. By E13.5, significant numbers of Iba1+ cells were observed in the mantle layer. Examination of sectioned tissues suggested that Iba1+ cells entered the neural tube through its basal surface, apical surface or blood vessels. When fragments of E11.5 liver tissues genetically labeled with eGFP were transplanted to the mesenchyme next to the unlabeled E10.5 neural tube, eGFP+Iba1+ cells were found within the neural tube one day after transplantation, implicating that Iba1+ cells from the embryonic liver were able to migrate through the mesenchyme to enter the neural tube. In conclusion, microglial progenitors expressing Iba1 enter the neural tube through multiple sites, and the embryonic liver could represent a source of origin.The work was supported by the General Research Fund from the Research Grants Committee of the Hong Kong Special Administrative Region, China (Project No. 461909).
The neuroanatomy of deep brain stimulation for the treatment of Parkinson disease
Authors: Smith Lorinda K. , Dibble Lee , Foreman K. Bo 
Published: June 2021

The basal ganglia (BG) contribute to control of automatic movements such as postural reactions. In Parkinson disease (PD), neural degeneration alters the overall output of the BG, causing movement deficits. Deep brain stimulation (DBS) is an established treatment for disabling motor signs in PD that are unmanageable by medication alone. However, DBS has been associated with unwanted side effects including impairment of postural control, which may lead to falls and related injury. The purpose of this narrative literature review was to determine common neuroanatomical locations of DBS implantation and their effect on postural control and falls. This review is a preliminary step towards examination of postural control tasks in patients with DBS implants in order to gain insight into the role of the BG in postural control. The subthalamic nucleus (STN) and the globus pallidus internus are the most common areas of DBS implantation, with STN implants having a higher incidence of adverse postural control effects. DBS implantation in the pedunculopontine nucleus is being studied with mixed results. Understanding of postural control deficits of individuals with DBS for PD may be used to assist rehabilitation professionals in fall prevention efforts and ultimately inform neurosurgeons in placement and programming of DBS to minimize postoperative postural control deficits.Grant Funding Source: None