bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Ultrasound: novel finger probe versus classic probe
Authors: Corbett Rebecca , Delamarter Taylor , Benninger Brion
Published: June 2021

INTRODUCTION

Ultrasonography (USS) is the stethoscope of the future. USS probes have evolved to improve structural identification. This study investigated a novel shaped probe used by first‐year medical students (FMS) conducting a clinical procedure.

METHODS

Literature search was conducted on texts, specialty journals and websites regarding the use USS finger probe by FMS performing invasive techniques. FMS performed timed USS‐guided cannulation to the internal jugular (IJV) and subclavian (SCV) veins on a blue phantom torso, and identified them on a volunteer using a novel USS finger and a classic probe. A questionnaire asked about probe preference.

RESULTS

Literature search revealed no studies comparing finger and classic probes, nor USS‐guided central line techniques being conducted by FMS. FMS identified and cannulated the IJV and SCV using both probes within 6 minutes with statistical significance. Questionnaire revealed FMS preferred the finger probe.

DISCUSSION

USS is a safe, non‐invasive imaging medium proven successful for invasive procedures. This study demonstrated FMS could interpret USS while conducting a common procedure. Finger probe proved successful in structure identification and was preferred to the classic probe due to its combined tactile presence.

CONCLUSION

This pilot study of a novel finger USS probe was successful identifying structures by FMS, suggesting future studies.
Targeting the GCC endocrine signaling axis to reduce appetite in obesity
Authors: KIM GILBERT WON , WALDMAN SCOTT ARTHUR
Published: June 2021

In light of our discovery that the transmembrane receptor guanylyl cyclase C (GCC) regulates appetite through a novel gut‐brain endocrine axis, we aimed to further define hypothalamic GCC expression and, moreover, determine the consequence of obesity to this GCC signaling axis. Nuclei were microdissected from mouse hypothalamus and GCC expression was quantified by RT‐PCR. Mouse brains were also cryosectioned and hypothalamic slices were immunostained for GCC. Further, hypothalamus and intestine were harvested from lean and obese mice, and GCC and GCC ligand expression was quantified by RT‐PCR, immunoblot, and immunofluorescence. Our studies revealed the suppression of intestinal ligand expression with the concomitant overexpression of hypothalamic GCC in obese mice. Further, our studies suggested that GCC was enriched in the arcuate nucleus, a key regulator of appetite. Our results suggest a corruption of the GCC axis in obesity, which in part reflects an endocrine deficiency of GCC ligands that could be therapeutically targeted to supersensitized receptors by hormone replacement. Thus, GCC represents a new target to develop anti‐obesity pharmacotherapies against this accelerating pandemic. This research was supported by the Thomas Jefferson University Doctoral Student Research Fellowship.
Downregulation of DNase I expression by EndoG in kidney tubular epithelial cells
Authors: Zhdanov Dmitry D. , Fahmi Tariq , Wang Xiaoying , Savenka Alena , Basnakian Alexei G.
Published: June 2021

We have previously obtained evidence of the endonuclease network, in which all cytotoxic/apoptotic endonucleases are induced by deoxyribonuclease I (DNase I) through its DNA‐degrading activity. Because DNA breaks can be produced by any endonuclease, our next question was whether another endonuclease could have the same effect. To test this, we transfected rat kidney tubular epithelial NRK‐52E cells with endonuclease G (EndoG) gene in pECFP vector. The expression of EndoG‐CFP fusion protein was monitored for up to 24 hours by using quantitative fluorescent microscopy, while CFP (pECFP) expression was used as control. At 24 hours post‐transfection, cells were harvested and total RNA was isolated. mRNA expressions of eight endonucleases, including DNase I, DNase X, DNase gamma, DNase 1L2, DNase IIalpha, DNase IIbeta, L‐DNase II and caspase‐activated DNase (CAD) were measure using real‐time RT‐PCR. Our data showed EndoG overexpression mildly affected expression of other endonuclease, except DNase I, expression of which was downregulated to almost zero level. Agarose electrophoresis of DNase I gene amplification product showed that DNase I pre‐mRNA is alternatively spliced lacking ~100 bases at/near exon 4. This is the first evidence that EndoG or an endonuclease can downregulate another endonuclease by inducing alternative splicing.
The role of beta‐arrestin2 in clozapine's actions at the serotonin 2A receptor
Authors: Schmid Cullen L , Streicher John , Bohn Laura M
Published: June 2021

The G protein‐coupled serotonin 2A receptor (5‐HT2AR) is a prominent target of atypical antipsychotic drugs, including clozapine. Although clozapine has classically been defined as an antagonist at the 5‐HT2AR, it is unique in that it also induces 5‐HT2AR internalization and promotes phosphorylation of Akt downstream of the receptor. We have previously demonstrated that serotonin also induces such signaling events in a manner that requires interactions between the receptor and the intracellular regulatory and scaffolding protein, barrestin2. Here, we demonstrate that unlike serotonin, clozapine mediates receptor internalization and induces Akt phosphorylation independent of barrestin2, in mouse embryonic fibroblasts and primary cortical neurons. Moreover, we show that the in vivo effects of clozapine, as measured by its ability to block MK801‐induced hyperlocomotion in mice, are also independent of barrestin2 expression. Therefore while clozapine induces some similar receptor mediated events as serotonin, it utilizes a unique signaling mechanism to do so. Further elucidating of these mechanisms in vivo may allow for the development of more effective atypical antipsychotic drugs.
The role of the β9–10 linker in nicotinic acetylcholine receptor selectivity
Authors: Nemecz Akos , Ho Kwok-yiu , Talley Todd , Taylor Palmer
Published: June 2021

The cys‐loop family of ligand‐gated ion channels plays an important role in the chemical‐to‐electrical transduction of neuronal signaling. The nicotinic acetylcholine receptors (nAChRs) may be linked to nicotine addiction, and show possible genetic linkages to such diseases as Alzheimer's and schizophrenia. The discovery of a homologous homomeric soluble snail acetylcholine binding protein provided a structural surrogate of the extracellular ligand‐binding domain. Systematic mutations of the soluble Aplysia californica achieved sequences resembling α7‐nAChR at the subunit interfaces. Here we look specifically at the beta 9–10 linker (C‐loop) and mutate the sequence to every human alpha sequence. These alpha C‐loop mutants were characterized structurally, via x‐ray crystallography, and functionally using a series of ligands selective for each alpha receptor subtype. In some situations ligands showed similar selectivity as the full‐length receptor subtypes, whereas in most situations the flexible C‐loop was not clearly not responsible for the selective property of the ligands tested. (Supported by: U01‐DA 019372, GM07752‐29)
Effect of some edible mushrooms on nitrite treated beef concentrate using Ames test
Authors: Tongyonk Linna , Kangsadalampai Kaew , Sabaichai Wanwisa , Panmuang Thitirat , Warisnoicharoen Warangkana , Meksawan Kulwara , Pongthananikorn Suyanee
Published: June 2021

This study evaluated the possibility that extracts from some edible mushrooms (button, shiitake, oyster and abalone) could modulate the formation of the mutagen precursor during extended period cooking of beef and the direct mutagen produced from interaction between nitrite and beef concentrate. The concentrates from beef boiled with the mushroom samples did not show the mutagenicity when tested with the Ames test using Salmonella typhimurium strains TA98 and TA100 in the absence of metabolic activation. After treated with nitrite, they exhibited the mutagenicity towards both strains. The results showed that the addition of mushroom extracts to the beef concentrate before treated with nitrite did not reduce the mutagenicity. However, the actual mutagenicity of the mixtures of mushroom extracts and beef concentrates treated with nitrite was less than the calculated value. Exceptions were found in button and oyster mushroom extracts on TA98. Thus, it was indicated that some mutagen precursors presented in all concentrates could interact with nitrite and addition of these mushrooms could not reduce the formation of the mutagen precursors.
Antioxidant related investigations on bark of Harungana madagascarensis from Eastern DR Congo
Authors: Kim Hee Seon , Koh Kwangoh , Park Eun Hee , Balagizi Innocent , Kim Hye Ju
Published: June 2021

Harungana(Harungana madagascarensis) is a commonly used medicinal plant in DRCongo. The aim of the study was to investigate potentials to develop an ethnomedicinal drug by evaluating the antioxidant activities and cytotoxicity of Harungana stem bark extract. A methanol(MeOH) extract and fractions of MeOH of Harungana stem bark were studied in vitro for total antioxidant activities by DPPH and ABTs and total phenol content was assessed with Folin‐Ciocalteau reagent. MTT and Griess reaction were used to test toxicity and nitric oxide(NO) production in RAW264.7 cells. We found no toxicity of ethyl acetate and aqueous extracts on RAW264.7. The methanol extract showed significant antioxidant activities(IC(50)22.89μg/mL and 20.37μg/mL in the DPPH and ABTs, respectively). The MeOH extract(100mg) yielded 271.96mg tannic acid‐equivalent phenolic content. Ethyl acetate and butanol extracts also expressed similar antioxidant effects as MeOH extract. Hexane and butanol extracts decreased NO production by RAW264.7 (IC(50)22.2 μg/mL). The present study provides an evidence that methanol, butanol and ethyl acetate extracts of Harungana stem bark are potential sources of natural antioxidants.
Determination of the Minimum Exposure Time for Effecting Cytoprotection in Human Umbilical Vein Endothelial Cells (HUVEC) for Caffeic Acid Phenylethyl Ester (CAPE) and Amide (CAPA)
Authors: Yang John , Bowman Phillip D , Stavchansky Salomon
Published: June 2021

We have previously shown that CAPE and CAPA protect HUVEC from oxidant stress.1 This activity was correlated with the production of heme oxygenase‐1 (HO‐1). The objective of this study was to determine the minimum exposure time necessary to provide cytoprotection and HO‐1 production. HUVEC were exposed to cytoprotective doses of CAPE and CAPA for 0.5,1,2,3,4 and 6 hrs. The compounds were removed at the end of each time period and placed in fresh media. Levels of HO‐1 were then evaluated by gel electrophoresis and immunoblotting, and cytoprotection against H2O2 toxicity was measured. CAPE and CAPA both showed a significant increase in HO‐1 expression over vehicle control within 30 min of exposure. HO‐1 levels for both CAPE and CAPA peaked with a 4 h incubation time with no significant differences beyond 4 hours. Significant cytoprotective effects against hydrogen peroxide for both CAPE and CAPA were found with as little as a 1 h exposure time. CAPE and CAPA both showed significant effects on HUVEC HO‐1 expression and cytoprotection with only a brief exposure. It appears that the compounds do not need to be continually exposed to the cells in order for the beneficial properties to be expressed. Whether this is due to cell loading of the drug or that minimum exposure to drug triggers a switch that leads to the effect is under investigation. Funding provided by the US Army Medical and Material Command
Mitochondrial proliferation is not affected by inhibition of the intracellular renin‐angiotensin system
Authors: Ruiz Louis , Rullan Rebecca Parodi , Javadov Sabzali
Published: June 2021

Inhibition of the renin‐angiotensin system (RAS) has shown to exert cardioprotection against hypertrophy and heart failure independent of their anti‐hypertensive effects. However, molecular mechanisms underlying the benefits of RAS inhibition mediated through the intracellular RAS system on cardiac cells remain to be elucidated. We examined the contribution of mitochondrial proliferation to the anti‐hypertrophic actions of the RAS inhibitors, losartan and aliskiren. An in vitro model of hypertrophy was induced on H9c2 myoblastic cells with angiotensin II (Ang II). Results demonstrated that hypertrophy‐induced stimulation of cell signaling was associated with an increase in cell surface area and ERK1/2 MAPK phosphorylation by 19% (p <0.05) and 39% (p <0.05), respectively. Treatment with RAS inhibitors prevented hypertrophy as evidenced by normalization of AngII effects. Fluorescence activated cell sorting (FACS) analysis revealed reduced mitochondrial proliferation in AngII‐treated cells which was not prevented by RAS inhibition. Conclusively, this study demonstrates that inhibition of the RAS attenuates AngII‐induced hypertrophy in H9c2 cells that is not associated with mitochondrial proliferation.
Role of Serum Response Factor (SRF) and NFkB in Acrolein‐induced Modulation of Inflammatory Gene Expression Profiling
Authors: Yousefipour Zivar , Newaz Mohammad Ali
Published: June 2021

Inflammatory signaling in acrolein toxicity in VSMC has been proposed but signaling mediators are unknown. The issue has been further complicated by the emergence and understanding of inflammatory proteins. Previously we reported acrolein‐induced vascular toxicity requires SRF dependent activation/expression of NFkB. We confirmed that SRF inhibition attenuates NFkB. In this study we explored expression of genes involved in inflammatory process and involvement of SRF or NFkB. VSMCs were treated with acrolein (0.5 μg/ml; 24 hrs) with or without pre‐incubation with Helenalin (NFkB inhibitor; 2 μM) or CCG (SRF inhibitor; 300 nM) for 30 min. RNA was isolated, gene expression was measured using PCR array examining 84 genes. Acrolein causes over‐expression of 6 genes (4–16 fold) and under‐expression of 8 genes (7–48 fold). Casp1 (Caspase 1; 12 fold) and Cx3cl1 (Chemokine Ligand 1; 12 fold), involved in cell death and exaggerated immune response, were over‐expressed. IL11 and Spp1 were reduced 36 and 24 fold respectively. SRF inhibitor enhanced expression of Abc1, a gene responsible for ATP binding and mRNA transcription by 15 fold. SRF and NFkB inhibition reduced Cx3cl1 expression (7 fold and 4 fold respectively) that was over‐expressed in acrolein treated cells. These observations suggests that acrolein induced activation of inflammatory signaling involves expression of Cx3Cl1 gene and is SRF and NFkB dependent.
Biomineralized matrices promote osteogenic differentiation of human mesenchymal stem cells: A mechanistic study
Authors: Shih Yuru Vernon , Phadke Ameya , Siu Michael , Lee Oscar K.S. , Chien Shu , Varghese Shyni
Published: June 2021

Human mesenchymal stem cells (hMSCs) are ideal cells for skeletal tissue engineering due to their expandability and ability to undergo osteogenic differentiation. Recently, we have shown that hMSCs cultured on biomineralized matrices undergo osteogenic differentiation in the absence of any osteogenic inducing soluble factors. This finding in conjunction with the occurrence of dynamic dissolution of the calcium‐phosphate phase of the matrix suggest that inorganic ions such as Pi play a direct functional role in directing osteogenic differentiation of hMSCs on mineralized matrices. hMSCs cultured on biomineralized matrices upregulated Runx2, while knockdown of the transmembrane phosphate transporter SLC20a1 abrogated such an increase, similar to that observed on culture in high Pi (5 mM; PM). These findings exemplify the role of Pi, which enters the cells through SLC20a1, in promoting osteogenesis of hMSCs. Furthermore, the intracellular and intra‐mitochondrial phosphate, as well as intracellular ATP content, were elevated during PM culture, but decreased after SLC20a1 knockdown. Our results demonstrate a previously unknown mechanism of the osteoinductivity of mineralized matrices involving inorganic ions where they serve as a substrate for ATP synthesis and possibly acting as an extracellular autocrine/paracrine signaling molecule. (NSC 99‐2911‐I‐009‐101; NSC 99‐2911‐I‐010‐501).
Coding of anuran vocalization by a single type of premotor neuron
Authors: Yamaguchi Ayako , Zornik Erik
Published: June 2021

Motor programs are composed of movements that are coordinated with precise timing. For example, human speech involves very rapid movements that control articulation on a msec time scale. How are temporally precise motor programs generated by the nervous system? We addressed this question by conducting an electrophysiological experiment using vocalizations of African clawed frog (Xenopus laevis) as a model. The central vocal pathway of Xenopus is a tractable system that allows experimental manipulation while the brain is engaged in “fictive vocalizations” in vitro. Male Xenopus produce advertisement calls consisting of alternating fast and slow trills, each of which contains trains of clicks repeated at ~60 and 30Hz, respectively. Using patch‐clamp whole‐cell recordings, we discovered a type of premotor neuron that codes for both click rates and trill durations. The neurons, termed fast trill neurons (FTNs), show NMDA receptor‐dependent plateau potentials that coincide with the fast trill. Furthermore, the neurons fire a series of action potentials during the fast trill with each spike preceding motor output by ~4 msec. Interestingly, the FTNs exhibit both subthreshold oscillations and spike timing preference exactly at 60 Hz, the frequency of the fast trills. We conclude that complicated temporal patterns of Xenopus vocalizations can be encoded by the intrinsic properties of a single type of premotor neuron.
DEVELOPMENT ENHANCES HYPOMETABOLISM AND THE DIVE RESPONSE IN NORTHERN ELEPHANT SEAL PUPS
Authors: Tift Michael Scott , Houser Dorian , Crocker Daniel
Published: June 2021

We investigated the development of the dive response and diving capacity by measuring; 1) changes in O2 consumption (VO2) 2) changes in venous blood gases and hemoglobin saturation and 3) comparing rates of O2 use between terrestrial apneas and submergences. Hypometabolism during breath‐holds increased across development, reaching a maximum suppression of 53% from RMR late in development. There was a 17% suppression in VO2 during voluntary breath‐holds at the end of the developmental period. Hypometabolism increased with breath‐hold duration and was further reduced during submergences. Similar patterns of increased O2 conservation across development and during submergence were seen in the slower rates of pO2 depletion. This study demonstrates the physiological cue for stimulating respiration in northern elephant seal pups is the build‐up of pCO2 across a breath‐hold. Reduced O2 storage directly limits diving capabilities and likely influences foraging success in seals forced to depart to sea prior to achieving full developmental diving capacity. Our findings highlight the critical importance the duration of the developmental period in seals has on increasing breath‐hold capacity and underlies the significant role that facial immersion has in down‐regulating blood O2 use in diving seals.
Formyl peptide receptor ligands exert differential effects on corticosterone secretion from the hypothalamo‐pituitary‐adrenal (HPA) axis
Authors: Naughton Vance Alexander , John Christopher David , Buckingham Julia Clare
Published: June 2021

The stress response results in increased secretion of cortisol in man and corticosterone (CORT) in rodents. Our previous studies have identified roles for annexin A1 (ANXA1) and its receptor, a member of the formyl peptide receptor (FPR) family (possibly Fpr2) within the hypothalamus and pituitary gland in regulating CORT secretion. The FPRs are expressed in abundance in the adrenal gland but their role has not been determined. We hypothesised that FPRs contribute to the local mechanisms regulating CORT release. Adrenal glands from male Wistar rats (n = 6, 220 – 250 g) were dispersed in Earle's balanced salt solution (EBSS) and collagenase (95% O2, 5% CO2, 37 °C, 2 h) then stimulated (4 h) with a submaximal concentration of ACTH1–24 [Tetracosactide, 10−7 mol.L−1] in the presence and absence of various FPR ligands. ACTH stimulation resulted in a 60% increase in CORT release (P < 0.001). Versus basal release, fMLF (Fpr1), Ac2–26 (Fpr2/3), and 15‐epi‐LXA4 (Fpr3) were inhibitory, whereas F2L (Fpr2) was stimulatory (P < 0.001). Versus ACTH alone, ACTH‐stimulated CORT release was reduced in cells treated with fMLF [10−7], peptide Ac2–26 [10−7], and 15‐epi‐LXA4 [10−9] by 80%, but was increased in the presence F2L [10−10] by 50% (P < 0.001). Our work showed certain Fpr1/Fpr3 agonists inhibit adrenal CORT release whereas Fpr2 appears to be stimulatory.

This was funded by the BBSRC.
Ocular blood flow decreases during passive heat stress in resting humans
Authors: Ikemura Tsukasa , Hayashi Naoyuki
Published: June 2021

The effects of passive heat stress (PHS) on ocular blood flow were investigated by measuring the ocular blood flow, end‐tidal CO2 (PETCO2), and blood pressure in 12 healthy subjects who were passively heated for 90 min by perfusing 50°C water through the suit. The blood flows in the superior temporal retinal arteriole (STRA) and the retinal and choroidal vessels (RCV) were measured by laser speckle flowmetry every 30 min during PHS. PETCO2 was clamped at the resting level by adding 5% CO2 to the inspired gas. The blood pressure did not change significantly throughout the induced PHS. The blood flow in the RCV decreased significantly from the resting baseline at 30, 60, and 90 min after the onset of PHS, with a peak decrease of 18±1% (mean±SE) at 90 min. The blood flow in the STRA decreased significantly at 60 and 90 min, with a peak decrease of 12±2% at 90 min. These findings suggest that PHS decreases ocular blood flow without changing the blood pressure or PaCO2.
Exercise‐induced increase in plasma volume and albumin content is enhanced by protein and CHO intake just after exercise
Authors: Okazaki Kazunobu , Takeda Ryosuke , Suzuki Akina , Naghavi Nooshin , Imai Daiki , Miyagawa Toshiaki
Published: June 2021

Plasma volume (PV) expands with plasma albumin content (Albcont) after a bout of exercise, which is known to be enhanced by post‐exercise protein and CHO intake. It is unknown which is a key condition to enhance PV and Albcont expansion; the timing of protein and CHO intake after exercise or the total amount of daily protein and energy intake.

METHODS

Seven young men (~23 yrs) completed two trials those of which differ in the timing of intake (immediately after exercise, 0H; and 2.5 hours later, 2.5H) of a mixture of protein and CHO (3.2 kcal and 0.18 g protein/kg). Subjects performed a bout of 72‐min intense and intermittent exercise (8 sets of 4 min at 80% VO2max intermittent by 5 min at 20% VO2max) by using an upright cycling ergometer. PV and Albcont (PV x [plasma albumin concentration]) were determined before exercise, at the end of exercise, every hour from the 1st to the 5th hour and at the 23rd hour after exercise during.

RESULTS

In 2.5H, Albcont and PV increased from before exercise by 0.5% and −3.5% at the 5th hour and by 1.6% and 1.8% at the 23rd hour, respectively. In 0H, on the other hand, Albcont and PV increased by 3.1% and −0.6% at the 5th hour and by 2.1% and 3.5% at the 23rd hour, respectively. The increase in Albcont and PV at the 5th and 23rd hour was significantly higher in 0H than in 2.5H.

CONCLUSIONS

Protein and CHO intake just after exercise is a key condition to enhance the increase in Albcont and PV.
Enterotoxigenic Escherichia coli (ETEC) inhibits intestinal vitamin B1 (thiamin) uptakeby human‐derived intestinal epithelial Caco‐2 cells
Authors: Chatterjee Nabendu Sekhar , Subramanian Veedamali S , Said Hamid M
Published: June 2021

Enteric infections leading to diarrheal diseases are a major global health problem. There are 2 to 4 billion diarrheal episodes each year leading to millions of deaths. While infection with ETEC is known to cause diarrhea, prolonged and severe case may also be associated with malnutrition. Water‐soluble vitamins, including thiamin, are essential micronutrients that our body can neither synthesize nor store them in significant amounts, and thus, must be obtained them from exogenous sources via specific intestinal transport systems. Here we examined the effect of ETEC infection on the intestinal uptake of the thiamin using human intestinal epithelial Caco‐2 cells. Our results showed that infecting Caco‐2 cells with ETEC, but not with nonpathogenic E. coli, leads to a significant inhibition in thiamin uptake. This decrease in uptake was associated with a decrease in the level of expression of human thiamin transporter‐1 and 2 (hTHTR‐1 and 2). Confocal imaging of live cells showed a decrease in the level of expression of the hTHTR‐1 and 2 proteins at the cell surface. These results show that thiamin uptake by Caco‐2 cells is inhibited during ETEC infection. We currently investigating the cellular and molecular mechanisms involved in this inhibition. [Supported by USIEF and DK56061grants]
Alterations in red blood cell rheological properties in healthy people living at low and mid‐altitudes
Authors: BASARAN KEMAL E , AYDOGAN SAMI , ARTIS AISE S , DOLU NAZAN
Published: June 2021

People with existing health problems or reduced fitness may feel effects at a much lower altitudes than those who are more physically able. On the other hand living at higher altitudes is different than visiting. A number of studies describe many hematologic changes at extremely high altitudes. However, little information is known about the effect of long‐term living at mid‐altitude on hemorheologic parameters. In this study, the changes of hemorheological properties were investigated on 2 groups of healthy people aged 18–46, who have been living at low (1300m) and mid (2300m) altitude at Erciyes Mountain in Kayseri. Blood samples were taken from the antecubital vein using EDTA as the anticoagulant. An aliquot of the whole blood was used to analyse routine hematological parameters. RBC, HGB and PCV values were higher at mid altitudes than those at low altitudes. However, there were no significant differences in MCV, MCH and MCHC as red cell indices between two groups. As rheological parameters, erythrocyte deformability and osmotic fragility values were lower for people who lived at mid altitude compared to low altitude but an increase was observed in RBC aggregation index. It is known that the hemorheological properties of red blood cell membrane may be changed under hypoxic conditions depend on different altitudes. As a result, these results contribute to the knowledge of the pathogenesis of high altitude disease and stress the significance of altered hemorheology as one of the mechanisms possibly involved in the vascular events observed high altitude conditions. Supported by ERU. The Scientific Research Coordination Unit (BAP). Project No: TOA‐11‐3320
Effect of time of day on methamphetamine anticipation and neural activation
Authors: Robotham Margaret Trina Nolita , Tariq Maliha , Le Sauter Joseph , Silver Rae
Published: June 2021

Previous research shows that participants administered low doses of methamphetamine express more pleasurable effects late in the evening than early in the morning (Hart et al. 2003). By testing the effect of amphetamine aerosol administration on behavior we aimed to determine 1) the brain mechanisms regulating circadian effects of drugs and 2) the brain regions activated in response to anticipation of the drug at different times of day. We measured wheel running activity in response to aerosol administration of amphetamine or water at either 0400h or 1000h in mice maintained in a “skeleton” photoperiod (lights on 0000–0030 and 1130–1200). On the last test day mice were not administered the drug. Brains were collected just prior to the usual time of administration. Administration of amphetamine induced dose dependent wheel running activity. Mice showed anticipatory activity to the drug but not to water. This response was greater at 0400h than at 1000h. This suggests that the circadian system influences brain mechanisms involved in action of drugs of abuse. Brain sections were stained for cFOS, a marker of neuronal activity and regional brain activation, and compared at different times of day.
Egr‐1 mediates the suppressive effect of IL‐1 on PPARg expression in human OA chondrocytes
Authors: Nebbaki Sarah , El Mansouri Fatima Ezzahra , Zayed Nadia , Benderdour Mohamed , Martel-Pelletier Johanne , Pelletier Jean-Pierre , Fahmi hassan
Published: June 2021

Background

Peroxisome proliferator‐activated receptor gamma (PPARg) is a ligand activated transcription factor. Several lines of evidence indicate that PPARg have protective effects in osteoarthritis (OA). We have previously shown that IL‐1 down‐regulated PPARg expression in OA chondrocytes. In the present study we will investigate the mechanisms underlying this effect of IL‐1.

Methods

Chondrocytes were stimulated with IL‐1, and the level of PPARg and Egr‐1 protein and mRNA were evaluated using WB and Real Time‐RT‐PCR, respectively. The PPARg promoter activity was analyzed in transient transfection experiments. Egr‐1 recruitment to the PPARg promoter was evaluated using ChIP assays. Small interfering RNA (siRNA) approaches were used to silence Egr‐1 expression.

Results

We demonstrated that the suppressive effect of IL‐1 on PPARg expression requires de novo protein synthesis. ChIP analyses revealed that IL‐1 induced Egr‐1 recruitment at the PPARg promoter. IL‐1 inhibited the activity of PPARg promoter and overexpression of Egr‐1 potentiated the inhibitory effect of IL‐1, suggesting that Egr‐1 may mediate the suppressive effect of IL‐1. Finally, Egr‐1 silencing with siRNA blocked IL‐1‐mediated down‐regulation of PPARg expression.

Conclusion

These results indicate that Egr‐1 contributes to IL‐1‐mediated down‐regulation of PPARg expression in OA chondrocytes.
Acute exposure to fatty acids alters hepatic genes controlling branched‐chain amino acid degradation, inflammatory and acute phase response signaling, and liver x receptor/retinoid x receptor function
Authors: Brown Amanda L. , Shelness Gregory S.
Published: June 2021

Many transcriptional profiling studies have been performed to understand chronic hepatic steatosis. However, less is known about the gene expression changes in hepatocytes upon acute increases in fatty acid (FA) flux, as would occur during exercise‐induced lipolysis, prolonged fasting, etc. To address this question, we used a rat hepatoma cell line, McArdle RH7777, commonly used to model triglyceride (TG) mobilization and VLDL secretion. Cells were cultured for 24 h in the presence of 0.8 mM oleic acid complexed to BSA. Under these conditions cellular TG levels increased ten‐fold, as compared to BSA controls. Microarray analysis revealed that the top canonical pathways altered by oleic acid were 1) FA metabolism, 2) branched‐chain amino acid degradation, 3) acute phase response signaling, 4) lipopolysaccharide/interleukin‐1 mediated inhibition of retinoid x receptor function, and 5) liver x receptor/retinoid x receptor activation. These results indicate that acute exposure of hepatocytes to FA impacts several gene expression programs, including those involved in inflammation and the acute phase response. Candidate genes will be further investigated by RT‐PCR to elucidate the temporal and concentration dependence of gene expression changes associated with hepatic exposure to physiologic and pathophysiologic concentrations of FA. Support: RJR‐Leon Golberg Post‐Doctoral Fellowship to A.L.B.
Transcutaneous Carbon Dioxide Monitoring During Acute Respiratory Distress Syndrome Due to Smoke Inhalation and Burns
Authors: Belenkiy Slava , Ivey Katherine , Batchinsky Andriy , Langer Tom , Necsoiu Corina , Vecchi Vittoria , Baker William , Chung Kevin , Salinas Jose , Cancio Lee
Published: June 2021

We evaluated the accuracy of continuous noninvasive transcutaneous carbon dioxide (tPCO2) monitoring utilizing the SenTec Digital Monitoring System in a model of ARDS due to smoke inhalation and burns.

Subjects

anesthetized female Yorkshire pigs (47.4 ± 0.9 kg) received wood bark smoke inhalation injury and 40% total body surface area full thickness flame burn. A SenTec sensor heated to 43.5°C was used. Correlation of tPCO2 with arterial PaCO2 measured intermittently with i‐STAT blood gas analyzer.

Results

all animals developed ARDS at 23±2.08 hrs. Mean survival time was 51±14.9 hrs. A total of 88 paired measurements of PaCO2 and tPCO2 were performed. The mean overall bias between PaCO2 and tPCO2 under stable conditions (Bland‐Altman analysis (BAa)) was 0.75±5.34 mm Hg with overall correlation (R2 = 0.79, P<0.0001). Eighty‐nine percent of measurements were within the acceptable clinical range of agreement of ± 7.5mm Hg. This relationship deteriorated under hemodynamic instability with overall bias increasing to 17.3±18.5 mm Hg (BAa) and poor correlation (R2= 0.02, P=0.53) and only 33% of measurements were within the acceptable clinical range of agreement.

Conclusions

Transcutaneous CO2 monitoring is a reliable surrogate for PaCO2 in the setting of severe lung injury and hemodynamic stability. Additional information must be considered during hemodynamic instability for accurate estimation of PaCO2.
Simvastatin Treatment Attenuates Increased Respiratory Variability and Apnea/Hypopnea Index in Rats with Congestive Heart Failure
Authors: Marcus Noah J , Haack Karla KV , Zucker Irving H , Schultz Harold D
Published: June 2021

Cheyne‐Stokes respiration (CSR) is associated with increased morbidity and mortality in patients with congestive heart failure (CHF). In CHF patients, enhanced carotid body chemoreflex (CBC) sensitivity is associated with CSR. Reduced carotid body nitric oxide and nitric oxide synthase (NOS) levels play an important role in the enhanced CBC observed in CHF, and Simvastatin (SIM) treatment increases NOS expression. We hypothesized that, in a rodent model, development of CHF would be accompanied by enhanced CBC as well as increased respiratory variability (RV) and apnea/hypopnea index (AHI), and that SIM treatment would attenuate these changes. Using plethysmography, we measured ventilatory responses to hypoxia and hypercapnia, and calculated RV and AHI from measurements taken during resting breathing. Left ventricular (LV) function was quantified via echocardiography. We found that CHF was associated with enhanced ventilatory responses to hypoxia and hypercapnia and increased RV (sham vehicle SD1 0.07±0.12 vs. CHF vehicle SD1 0.133±.03) and AHI (sham vehicle 4±2 vs. CHF vehicle 14±1). SIM treatment prevented these increases (CHF statin SD1 0.07±0.01, and CHF statin AHI 6±2). Our findings demonstrate a relationship between increased CBC sensitivity and respiratory instability observed in CHF, and suggest that SIM may be an effective treatment for CSR in patient populations with high chemosensitivity.
The effect of calorie restriction on the genome stability in DNA repair defective cells
Authors: Lo Yi-Chen , Leow Siew Keng , Wu Pei-Shang
Published: June 2021

It has been found that calorie restriction (CR) can extend the average and maximum life span from yeast to primates and delay the onset of age‐associated pathologies. Mismatch repair and double strand break repair systems are major DNA repair pathways whose function are critical for maintaining genome stability. The inactivation of these systems in human pathway has been reported to cause cancer predisposition such as Hereditary Nonpolyposis Colorectal Cancer, Werner and Bloom syndromes. By using Saccharomyces cerevisiae model system for CR and aging studies, DNA repair defective cells (msh2Δ, msh3Δ, msh6Δ and sgs1Δ) were cultured with normal (2% glucose) and CR (0.5% glucose) medium. Genome stability studies were analyzed by CANr, Homr and Lysr mutation assay. Results show that CR can significantly extend the lifespan of all wild‐type and mutants. Besides, CR shows significant decrease in HOMr mutation frequency by 2.7 × 104‐fold in msh2Δ mutant, whereas by 2.4 × 106‐fold and 1.4 × 106‐fold reduction in msh3Δ mutant for HOMr and LYSr assay respectively. In addition, for sgs1Δ mutant, there are significant decreases in HOMr and LYSr assay by two‐fold. Under normal condition, msh2Δ, msh3Δ and sgs1Δ cells found to have regrow phenotype upon aging. However, this phenotype was diminished under CR condition. Thus, CR promotes genome stability in DNA repair defective cells especially in msh2Δ, msh3Δ and sgs1Δ mutants.
THE NERVES OF THE FACE:AN ANATOMICAL MODEL OF HEAD IN WAX BY TRAMOND, OBSERVATION AND PHOTOGRAPHICAL TRI‐DIMENSIONAL RECONSTRUCTION
Authors: Le Floch-Prigent Patrice Pierre , DRIFI FARIDA
Published: June 2021

The aim of the study was to check the anatomical veracity of the model of wax N°262, from the Orfila's Museum (Paris) made by Tramond, entitled “nerves of the face”. We successively took several numerical photographs with several view angles; anatomically described the nerves of the face as they were represented on this model; correlated the anatomical veracity of this representation with the classical textbook's data; approached the technical bases of fabrication; and collected successive photographs of the model every 5°, all along 180°, thus allowing animated rotation on computer, using the Quick Time Virtual reality program. The oversize of the model excluded a set on real human skeleton. The building technique of the model was deduced from known data but could not be completed reported. The anatomical veracity of the sample was excellent. The difficulties of realization in wax of an oversized model of the nerves of the human face were solved in the late 19th century, in Paris by Tramond's factory. They remained unequalled. The work of numerisation and its free disposal on the internet permit to make available for everybody this sample of the collection of the Orfila's museum which was evacuated on december 2009, after its closure.
Dietary avocado oil prevents the impairment in the complex III and ROS production in kidney mitochondria from diabetic rats by improving the electron flow through cytochrome c1
Authors: Cortes‐Rojo Christian , Saavedra‐Molina Alfredo , Samano‐Garcia Carlos Alberto , Ortiz‐Avila Omar , Calderon‐Cortes Elizabeth , Ortiz‐Madrigal Denia , Hernandez‐Mata Georgina , Rodriguez‐Orozco Alain Raimundo
Published: June 2021

ROS production at mitochondrial complex III (CIII) has been identified as one of the main factors leading to diabetic nephropathy. ROS production at CIII during diabetes occurs due to damage in some of its subunits, being oxidative damage a main contributor for this phenomenon. Thus, the attenuation of the damage in the CIII may serve as an approach to ameliorate diabetic renal dysfunction. Because its antioxidant content, we aimed to investigate whether avocado oil (AO) could decrease both the impairment in CIII and ROS production in kidney mitochondria from STZ‐induced diabetic rats. 90‐days of dietary AO administration prevented the impairment in CIII activity and decreased ROS production when the complex was further damaged by Fe‐induced oxidative stress. Impairment in electron flow through cytochrome c1 subunit was identified as the cause of CIII impairment and avocado oil also prevented this effect. Together, these results suggest that dietary avocado oil decrease the damage in the CIII by avoiding haem c1 destruction, which may be related with the high content of C18:1 and antioxidants in AO. This work was funded by CONACYT (130638 to CCR), and CIC‐UMSNH (CCR) grants.
EVALUATION OF ACUTE TOXICITY (IN MICE) AND SUBCHRONIC TOXICITY (IN RATS) OF AQUEOUS EXTRACT OF TAPINANTHUS BANGWENSIS LEAVES GROWN ON ORANGE TREES
Authors: Nwoke Stella C , Magbagdeola Abiola O. , Ebuehi Albert O. , Imaga Ngozi A , Omojufehinsi Moyosore , Gbotolorun Stella , Ajayi Godwin O. , Ani Anthony
Published: June 2021

Mistletoe (Tapinanthus bangwensis spp.) is a semi ‐ parasitic evergreen plant that has been used traditionally in Nigeria for the treatment and management of ailments such as diabetes, disorders in infertility, cancer, arthritis, rheumatism, epithelial tumors, hypertension, asthma, nervousness and epilepsy. This study seeks to evaluate the toxicological property of the aqueous extract of T. bangwensis leaves.. Acute toxicity of the extract was evaluated in Swiss albino mice by oral administration of the animals with graded doses of the extract between 500 to 20,000 mg/kg body weight and observed continuously for the first 4 h, every hour for the next 24 h and at least once daily for 14days. The results indicated that the LD50 of the extract is >; 20,000 mg kg‐1 body weight. In the subchronic toxicity study, T. bangwensis extract was administered by gavage at doses of 100, 250, 500 and 1000 mg/kg daily for 4 weeks to Swiss albino rats. Results showed no significant differences in behavior, food intake, body and organ (liver, heart and renal, ovary and uterus) weights of the experimental animals.. Also, measured indices revealed no statistically significant changes in hematological and biochemical indices of the test animals relative to the control group (p>;0.05). Necropsy and histopathological examination, did not reveal any remarkable changes. These preliminary toxicological results being the first of its kind suggests that aqueous leaf extracts of Tapinanthus bangwensis have no adverse toxicological consequences and also safe for various medicinal purposes.
The relationship between function and structure of the heme‐scavenging protein IsdX1
Authors: Kenrick Anthony , Polzin Kayla , McEvoy Megan
Published: June 2021

Transition metals are of great importance in biology due to their use as cofactors for metabolic cellular processes. Since these metals are necessary for cellular function, metal acquisition and regulation are integral for proper growth and development. For instance, iron is used in both redox reactions and the electron transport chain, so it is essential for bacteria to grow and divide. Because of this, many mechanisms exist for iron acquisition, such as the iron‐regulated surface determinant (Isd) system found in several genera of bacteria, including Bacillus anthracis, the causative agent of anthrax. In the Isd system of B. anthracis, the protein IsdX1 is responsible for scavenging heme from host hemoglobin so that iron can be acquired after heme uptake and degradation. In order to understand the functional mechanics of IsdX1, it is necessary to characterize the protein with and without heme bound. This is accomplished through a combination of limited proteolysis and circular dichrosim, which both provide insight into the structural stability of a protein. Through these analytical tools, it is clear that IsdX1 is very stable, but does experience some structural change upon heme binding.
Mean Total Cholesterol/HDL‐Cholesterol Ratio and hs‐CRP Levels Among Foreign‐born Afro Caribbeans and their United States‐born Counterparts in South Florida
Authors: Davis Errol , Huffman Fatma , Dehpahlavan Jaleh
Published: June 2021

Objective

In a cross‐sectional study we examined total cholesterol/high‐density lipoprotein cholesterol (TC/HDL‐Cholesterol) and high‐sensitivity C‐reactive protein (hs‐CRP) values in 66 Foreign‐born Afro Caribbean (FBAC) living in the US for less than 10 years, 62 US‐born Afro Caribbean American (USBACA) and 61 African American (AA) adults (18–40 years).

Results

There were no significant statistical differences between the groups with respect to TC, HDL‐Cholesterol or TC/HDL‐Cholesterol ratio. However, the AA participants compared to the FBAC and USBACA participants had significantly (p< 0.01) higher hs‐CRP levels (2.2 ± 2.7 vs. 1.1 ± 1.3 and 1.3 ± 1.6 mg/L). This statistical significant difference was also seen in the female ethnic groups but, not the males. There were no correlation between blood lipids and hs‐CRP, however, there were positive correlation between TC and TC/HDL‐C ratio but, negative correlation between HDL‐C and TC/HDL‐C ratio.

Conclusion

We have demonstrated statistical significant differences in hs‐CRP levels between different ethnic subgroups of the same racial group. Understanding the ethnic and cultural differences and the variations in health indicators among different ethnic groups of the same race can help us to develop culturally sensitive programs and strategies for the improvement of health outcomes

Source of funding: Florida International University Foundation
Effects of mango supplementation on body weight and composition and clinical parameters of obese individuals
Authors: Evans Shirley Faye , Meister Maureen , Peterson Sandra , Perkins‐Veazie Penelope , Clarke Stephen , Payton Mark , Smith Brenda , Lucas Edralin
Published: June 2021

Previously, mango fruit (Mangifera indica L.) has been shown to improve body composition and blood glucose in an animal model of diet‐induced obesity. The objective of this pilot clinical study was to examine the effects of supplementation of freeze‐dried mango fruit on body weight and composition and clinical parameters (i.e. glucose, lipid, liver function, and hematological parameters) in obese adults. Twenty adults (11 males and 9 females) with body mass index of 30–45 kg/m2 participated in the study and were given 10 g of freeze‐dried mango daily for 12 weeks. Body composition, anthropometric and clinical parameters were measured at baseline and at the end of supplementation. There were no significant changes in body weight and composition, blood lipids, liver function, and hematological parameters after mango supplementation. However, similar to animal findings, mango significantly reduced blood glucose concentrations. Our findings indicate that regular consumption of mango does not increase body weight and blood glucose of obese individuals. (Supported by the National Mango Board)
What are U.S. Children Under Two Eating? Results from NHANES (2003–2008)
Authors: Keim Sarah , Branum Amy M , Peck Joshua
Published: June 2021

We characterized the diets of U.S. children under age two, including transitions to solid food and diet differences by race and poverty status. We included children from the U.S. National Health and Nutrition Examination Survey (NHANES), 2003–08, with 1‐ day dietary recall and questionnaire data available (n=2,660). We categorized foods and calculated weighted prevalence proportions of food groups by age, race, and poverty. Juice (7%), other grain dishes (6.7%), infant cereal (6.6%), and other sweetened products (6.6 %) were more common in the diets of non‐Hispanic black children than non‐Hispanic white children (p<0.0001), while apples (3.2%), other fruits (2.3%), and cheese (1.4%) were less common. Compared to non‐Hispanic whites, crackers/salty snacks (3.9%), cheese (1.5%), bread (1.3%), and most fruits and vegetables made up a lesser proportion of the diet of Mexican‐ American/other Hispanic children, while other grain dishes were more common (6.5%). Juice (6.6%), sweetened products (6.3%), and potatoes (2.1%) were more common and other vegetables (3.8%), apples (3.6%), and other fruits (2.5%) were less common among poor children compared to non‐poor children (p<0.0001). This study identified healthy and unhealthy dietary patterns and their variation by race and income, thereby highlighting areas for improvement in the diets of very young children. No external funding support was obtained.