bluuebunny/crossref_metadata_2025 huggingface dataset:
Microarray Studies on the Effects of Palm Fruit Juice in Diabetic Nile Rats
Authors: Leow Soon Sen , Bolsinger Julia , Pronczuk Andrzej , Hayes Kenneth C , Sambanthamurthi Ravigadevi
Published: June 2021

The Nile rat (NR) models diet‐induced human type 2 diabetes (T2DM). In previous experiments (Brit J Nutr 106:1664, 2011), palm fruit juice (PFJ) blocked T2DM in male NR, while untreated rats exhibited advanced disease stages. The molecular mechanisms whereby PFJ exerts anti‐diabetic effects are unknown, prompting microarray gene expression analysis. Livers were obtained from NR undergoing 4 diet plans: hiCHO alone (diabetic control), 4800ppm resveratrol (RES) in food, 4800ppm PFJ in food, or 1500ppm PFJ in drinking water. Compared to hiCHO (most diabetic), hepatic liver gene expression profiles were enhanced for RES and PFJ‐food, while PFJ‐water gene expression changes were subtler. Random blood glucose was lowered (p<0.05) in both PFJ groups, but only slightly by RES (n.s.). Compared to hiCHO, PFJwater had 17 genes up‐regulated, 29 down‐regulated. PFJ‐food had 71 genes up‐regulated, 108 down‐regulated. RES had 90 genes upregulated, 76 down‐regulated. As a preliminary observation, the insulin signaling pathway, especially phosphatidylinositol (PI) 3‐ kinase, was significantly down‐regulated by PFJ‐food and RES, PFJ‐water being less marked. PI 3‐kinase has been reported to suppress glucose‐stimulated insulin secretion (Diabetes 51:87, 2002), suggesting PFJ and RES may modulate this activity in NRs to favor insulin secretion.

Funding source: Foster Biomed Res Lab and the Malaysian Palm Oil Board
Cardiovascular responses evoked by acetylcholine in prelimbic cortex is mediated by nitric oxide – guanylate cyclase mechanism in rats
Authors: Fassini Aline , da Silva Leandro Antero , de Aguiar Correa Fernando Morgan , Joca Samia Regiane Lourenço , Resstel Leonardo Barbosa Moraes
Published: June 2021

The stimulation of PL with acetylcholine (ACh) caused depressor response mediated by muscarinic receptors. Studies in literature demonstrated that stimulation of muscarinic receptors induced cyclic GMP formation mediated by nitric oxide. Hence, the objective of this study was to investigate if cardiovascular response caused by muscarinic receptors stimulation is mediated by nitric oxide and cyclic GMP formation. Male Wistar rats (240–280g) were used and guide cannulae were implanted in the PL for drug injection. The cardiovascular responses evoked by ACh (30nmol/200nL) microinjected into the PL were measured before and 15 min after PL treatment with, J 104129 fumarate ‐ M3 antagonist (6nmol/200nL), pirenzepine ‐ M1 antagonist (6nmol/200nL), N‐Propyl ‐ inhibitor of neuronal nitric oxide synthase (nNOS) (0,04nmol/200nL), carboxy‐PTIO ‐ scavenger NO (1nmol/200nL) or ODQ ‐ guanylate cyclase inhibitor (1nmol/200nL). A polyethylene catheter was implanted in the femoral artery for MAP and HR records. The statistical test utilized was two‐way ANOVA. The pre‐treatment with pirenzepine did not blockade the decrease of the MAP (F1,220=6.526; P=0.0113) and increase of the HR (F1,220=0.2313; P=0.6310), while J 104129 fumarate (MAP: F1,220=200.7; P<0.0001; HR: F1,220=170.1; P<0.0001), N‐Propyl (MAP: F1,264=79.04; P<0.0001; HR: F1,264=257.4; P<0.0001), C‐PTIO (MAP: F1,176=115.4; P<0.0001; HR: F1,176=255.7; P<0.0001) or ODQ (MAP: F1,220=165.7; P<0.0001; HR: F1,220=161.3; P<0.0001) blocked depressor and tachycardic responses caused by ACh microinjection into the PL. This results demonstrated that the cardiovascular responses caused by ACh in PL are mediated by local nitric oxide – guanylate cyclase mechanism. Financial Support: CAPES and FAEPA.
Psychopharmacology of a prominent HIV antiretroviral drug
Authors: Schetz John A. , Forster Michael J. , Maeso Javier González
Published: June 2021

Over half of HIV patients taking the antiretroviral (ARV) drug efavirenz under prescribed dosing conditions experience psychiatric adverse drug reactions, and, despite earlier claims, these side effects can persist. Yet the mechanistic explanation for ARV drug adverse psychiatric events is unknown, prompting us to investigate the psychopharmacology of efavirenz. Profiling the GPCR psychopharmacology of efavirenz pinpointed its interactions with the serotonin 5‐HT2A receptor (5‐HT2AR), a molecular site of action for hallucinogens such as lysergic acid diethylamide (LSD). Efavirenz activates 5‐HT2ARs though its efficacy is comparatively lower than that of LSD. In rodents, an LSD‐like interaction with the 5‐HT2AR appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz depress open field activity in a novel environment. Similar to LSD, efavirenz induces head‐twitch responses in wild type, but not 5‐ HT2AR–knockout mice. We conclude efavirenz has an LSD‐like psychoactivity mediated by the 5‐HT2AR. Our finding correlates with subjective reports from HIV patients experiencing specific dose‐dependent adverse drug reactions to efavirenz, such as hallucinations and night terrors, and also may explain reports of the recreational use of this ARV drug.

Support: R01 MH063162, R01 MH084894, UNTHSC RI6015
The in vivo Effects of Glucose and Lipid on the Granulocytes and Monocytes of Type 2 Diabetic Male Subjects
Authors: Horvath Peter , Oliver Stacy R. , Zaldivar Frank P. , Radom‐Aizik Shlomit , Galassetti Pietro R.
Published: June 2021

Atherosclerosis/cardiovascular disease are major causes of morbidity/mortality in type 2 diabetes (T2D), and have been associated with activation of innate immune cells, their diapedesis to the arterial intima, formation of the atherosclerotic plaque and release of thrombotic factors. While in T2D immune cell activation likely depends on dysregulated metabolic conditions, we have limited knowledge of the interaction between individual metabolic factor typical of T2D (hyperglycemia, hyperlipidemia), innate immune cell activation, and the progression of atherosclerosis. We therefore measured by flow cytometry cell surface expression of CD11b, CD14, CD16, CD62L and CD66b, known markers of granulocyte (Gc) and monocyte (Mc) activation, in 5 T2D subjects, during 4‐h i.v. infusions of glucose and lipids, performed separately or simultaneously. We hypothesized that both glucose and lipids would increase Gc/Mc surface marker expression, and simultaneous infusion would have a synergistic effect. Surprisingly, though, glucose only had little effect, while lipids, alone or combined with glucose, increased expression of several markers (such as CD11b in Gc, see figure, and in Mc). Our results suggest lipids may be stronger acute contributors to innate cell activation than glucose per se, possibly helping shape preventive dietary guidelines in T2D.

Supported by NIH Grants P01HD048721 and UL1RR031985
A novel model for ischemic stroke ‐ the ANP gene disrupted (ANP−/−) mouse: molecular effects of hypertension in the development of stroke
Authors: Ventura Nicole Marie , Peterson Nichole T , Tse M Yat , Jin Albert Y , Andrew R David , Pang Stephen C
Published: June 2021

Cardiovascular disease (CVD) and stroke share many similar risk factors including hypertension. Alterations in the natriuretic peptide system (NPS) have shown to play a protective role in cardiac hypertrophy (CH) and myocardial infarction (MI). Given the similarities between CVD and stroke, these conditions may also share similar molecular mechanisms in their etiologies. The objective of this study is to develop a novel model for stroke using the chronically hypertensive, atrial natriuretic peptide (ANP) gene disrupted (ANP−/ −) mouse to assess the effect of hypertension on stroke development. ANP+/− (salt‐sensitive) mice treated with either high (8%) or normal (0.8%) salt diet for 6 weeks were subjected to left middle cerebral artery occlusion (MCAO) for 30 min and allowed to recover for 24 hr. Results have demonstrated left ventricular (LV) hypertrophy and increased infarct volumes in mice treated with high dietary salt. Furthermore, we have characterized the alterations occurring in four major vasoactive systems in the brain; the NPS, the renin‐angiotensin system (RAS), the nitric oxide system (NOS) and endothelin system (ETS) using real‐time quantitative PCR (qPCR). Since ablation of ANP induces CH, understanding the molecular mechanisms of the above systems in the brain will allow us to assess if ANP plays a protective role for stroke as it does for MI. Support: HSFO and Canadian Foundation for Innovation.

Grant Funding Source: Heart and Stroke Foundation of Ontario and Canadian Foundation for Innovation
Anatomy and development of brainstem vasculature in the spiny dogfish, Squalus acanthias
Authors: Gilland Edwin , Rahmat Sulman
Published: June 2021

Vertebrates differ in how the internal carotid arteries (ICAs) connect to the aortic arches and how the basilar artery and its penetrating branches arise. To test phylogenetic patterns in brain vasculature, the carotid/basilar arterial system in embryonic and adult Squalus acanthias were examined using serial sections, vascular fills and microdissection. Dissections of other cartilaginous fish such as Hydrolagus, Raja, Mustelus and Scyliorhinus allowed identification of general patterns within Chondrichthyes for comparison to other vertebrates. At their earliest appearance, both the primitive ICA and a pial hindbrain angiogenic network contributed to the carotid‐basilar arterial tree. The paired ICAs are extensions of a midline sinus cephalicus which transforms into an unpaired encephalic trunk that enters the hypophyseal fossa and branches into paired cerebral carotids that are joined by the efferent pseudobranchial arteries. Within the fossa, the carotids divide into anterior and posterior divisions. The posterior run caudally along the lateral walls of the brainstem, giving off diencephalic, mesencephalic and cerebellar branches before fusing in the midline to form an unpaired basilar artery. The basilar gives off a quasi‐segmental series of transverse rhombencephalic branches. Fusion of the initially paired basilars is often incomplete beneath the medulla, resulting in a fenestrated adult basilar. Despite the significant diversity in adult brain vasculature, a highly conserved framework of brainstem vessels and morphogenetic processes is evident when comparing development of distantly related vertebrates such as dogfish sharks, zebrafish and humans.
Skeletal muscle satellite cells are reduced in cigarette smoke exposed mice
Authors: Jackson Jason Matthew , Palau Helena G. , Wagner Peter D. , Breen Ellen C.
Published: June 2021

Satellite cells (SC) are muscle stem cells important for muscle regeneration. We hypothesized that cigarette smoke (CS) exposure would decrease myofiber associated SCs, in part due to inhibited VEGF expression. SC number per myofiber was measured in wild type (WT), skeletal muscle VEGF gene‐deleted (skmVEGF−/−) and CS exposed mice. Growth of SC colonies in vitro was monitored in myofibers +/− CS extract (CSE) and/or VEGF−/−.

Methods

HSA‐Cre‐ ERT2 × VEGFLoxP mice were exposed daily to whole body CS for 4 wks or tamoxifen‐induced skmVEGF−/−. Nes‐GFP+/Pax7+ cells per isolated soleus myofiber were identified by confocal microscopy. Additional fibers were cultured for 4 days in the presence of tamoxifen +/− 2.5% CSE.

Results

Gastrocnemius VEGF levels were decreased to the same extent in skmVEGF−/− and smoke exposed mice (17.1 ± 3.9 WT, 5.2 ± 2 skmVEGF−/−, 4.2 ± 1.3 CS, p<0.01). Pax7+/Nes+ cells per soleus fiber were lowest in CS exposed mice but also reduced in the skmVEGF−/− group compared to WT (12 ± 2.2 WT, 7.2 ± 3.3 skmVEGF−/−, 3.5 ± 1.7 CS, p<0.01). Cultured soleus fibers treated with CSE formed long extensions of aggregated SC colonies. In vitro VEGF gene deletion resulted in smaller SC colonies compared to WT mice cultured under control and CSE conditions.

Conclusions

CS exposure leads to the loss of SC that may result from inhibited VEGF expression and incorporation into mature myofibers.

NIH/NHLBI HL091830‐01A1
Characterization of a MarR Homolog in Vibrio vulnificus
Authors: Lemon Tiffany LaShay , Grove Anne
Published: June 2021

A genomic locus of Vibrio vulnificus encodes a MarR family transcription regulator and an antibacterial efflux pump. The MarR homolog is predicted to autoregulate its own transcription and the expression of the antibacterial efflux pump, which would allow the bacterium to survive select antibiotic treatments. V. vulnificus's MarR homolog shares key residues with members of UrtR, a MarR subfamily that responds to urate for the attenuation of DNA binding. Because the V. vulnificus MarR homolog conserves the amino acid residues known to coordinate urate and to cause derepression of UrtR controlled genes, DNA binding should be attenuated in the presence of urate. Using electromobility shift assays, we have demonstrated specific protein‐DNA binding, and we are currently testing urate along with other possible ligands for the attenuation of this interaction. Identifying the natural ligand of the V. vulnificus MarR homolog will provide a better understanding of MarR family dynamics and unearth a mechanism of antibiotic escape that could be an effective target for treatments.
The regulation of microRNAs by Brahma‐related gene 1 in smooth muscle cells
Authors: Chen Meng , Herring Paul
Published: June 2021

MicroRNAs (miRs) regulate the phenotypic switch of smooth muscle cells (SMCs) that occurs under pathological conditions. Little is known about the transcriptional and epigenetic regulation of miR expression in SMCs. To identify miRs that are regulated by the Brahma‐related gene 1 (Brg1)‐containing SWI/SNF chromatin remodeling complex we performed a microRNA array screen of RNA isolated from colonic SMCs of mice harboring a smooth muscle‐specific knockout of Brg1. Quantitative RT‐PCR confirmed changes in expression of several miRs, including miRs‐143/5 and miR‐133. Expression of dominant negative Brg1 in wild‐type SMCs led to decreased expression of miRs‐143/145 but not miR‐133. The dominant negative Brg1 also blocked the myocardin‐mediated induction of miRs‐143/5 in 10T1/2 cells. Knockdown of SRF or myocardin decreased expression of miRs‐143/5 in SMCs, whereas miR‐133 expression was only repressed following SRF knockdown. In Brg1‐null SW13 cells, miRs‐143/5 but not miR‐133 were dramatically induced by myocardin only in the presence of Brg1. Chromatin immunoprecipitation assays revealed that Brg1 was important for myocardin‐mediated SRF binding to the miRs‐143/5 promoter. These data show that Brg1‐dependent chromatin remodeling regulates the expression of miRs‐143/5 and miR‐133 through distinct pathways in SMCs.

Supported by NIH DK61130 and AHA predoctoral fellowship.
Kabuki syndrome missense mutations disrupt the formation and histone methyltransferase activity of the MLL2 core complex
Authors: Shinsky Stephen Alan , Hu Michael , Vought Valarie E , Ng Sarah B , Bamshad Michael J , Shendure Jay , Cosgrove Michael S
Published: June 2021

Kabuki syndrome (KS) is a rare disorder characterized by multiple malformations and cognitive delay. Recent studies reveal that ~70% of KS individuals have missense or nonsense mutations in coding regions of the Mixed‐Lineage Leukemia 2 (MLL2 or ALR) gene. MLL2 catalyzes histone 3 lysine 4 (H3K4) methylation using a conserved SET domain in complex with WDR5, RbBP5, ASH2L and DPY30 (WRAD), together forming what is known as the MLL2 core complex. H3K4 methylation is required for transcription of genes involved in normal development. In KS, the majority of nonsense mutations delete the SET domain, while most missense mutations localize in or near the SET domain. This suggests that KS may result from a loss of function of MLL2 SET domain activity. To test this hypothesis, we substituted conserved amino acid positions in the closely related MLL1 homolog with KS missense mutations and found that all alter enzymatic activity, but in distinct ways. The R5340L variant does not complex with WRAD and loses H3K4 dimethylation activity. The R5471T, G5428D and T5464M variants form atypical complexes with WRAD, but with a weakened interaction with ASH2L. As a result, the R5471T and G5428D variants are enzymatically inactive, whereas the T5464M variant is defective for H3K4 dimethylation. Our results are consistent with the hypothesis that KS results from loss of MLL2 enzymatic activity. Work supported by NIH Grant #R01CA140522 to M.S.C.
Effect of pre‐tRNA 5’ leader sequence variation on the thermodynamic coupling and shared molecular recognition between RNA and protein components of RNase P
Authors: Niland Courtney Nicole , Yandek Lindsay E. , Guenther Ulf‐Peter , Jankowsky Eckhard , Harris Michael E.
Published: June 2021

Ribonuclease P, RNase P, recognizes different precursor tRNAs to process the 5’ ends of each and produce mature tRNAs. The RNA subunit of this ribonucleoprotein enzyme is catalytic, however, the protein subunit is essential in vivo and contacts nucleotides in the 5’ leader. Extensive genomic variation of this sequence makes identification of cognate binding motifs difficult. Since the RNA subunit also recognizes this region, we focus on the shared molecular recognition of the 5’ leader by RNA and protein. We developed a new method that allows us to quantify rate constants of individual substrates in a reaction with many alternative substrates. This allows analysis of all possible sequences in areas of protein and RNA contact, providing information on thermodynamic coupling between nucleotides. The effect of randomizing the protein binding site or both RNA and protein binding sites was determined. The results confirm that randomizing the protein binding site alters the of the holoenzyme reaction but not the ribozyme. Randomizing nucleotides at both protein and RNA binding sites alters the kinetics of both the ribozyme and holoenzyme. Illumina sequencing of the residual substrates during the reaction allows us to calculate the rate constants for each sequence. This data will reveal whether nucleotides at RNA‐RNA binding sites influence the thermodynamic contribution of those at protein‐RNA contacts and vice versa.
Molecular Mechanism of Aniline induced bladder cancer
Authors: Kannan Subburaj , Fielder Ronald , Tristan Johanna , Longoria Elena , Castillon Arianna
Published: June 2021

The National Institute for Occupational Safety and Health based in Cincinnati, Ohio, reported that an incidence of the bladder cancer risk was 6.5 times higher for workers considered to have definite exposure to ortho‐toluidine and aniline, and 4 times higher for workers with possible exposure among workers employed at a rubber chemical manufacturing plants. Aniline exposure has been shown to cause: i) An increase in iron overload and induction of oxidative stress in the spleen; ii) Enhanced transcriptional and translational up regulation of IL‐1, IL‐6, and TNF‐α. Increased activation of redox‐sensitive transcription factors NF‐κβ and AP‐1. iii) MAPK phosphorylation, AP‐1 activation, and enhanced TGF‐α gene expression. iv) increased expression of heme oxygenase‐1 (HO‐1), contributing pro‐oxidant mechanism, mediated through iron release, accumulation thus leading to oxidative damage. v) Increased expression of cyclins, Cyclin dependant Kinases (CDKs) and phosphorylation of retinoblastoma protein (pRB) protein; vi) Increases in both p‐IKKα and p‐IKK£]. Taken together, it is suggested that above sequence of events could represent the plausible underlying mechanism of aniline exposure induced oxidative stress.
Effects of Soy Protein Isolate and/or Omega‐3 Polyunsaturated Fatty Acid Supplementation on Bone Health in Female Rats with Polycystic Kidney Disease
Authors: Miller Matthew Scott , Oldaker Christopher , Maditz Kaitlin , Tou Janet C.
Published: June 2021

Polycystic kidney disease (PKD) is a genetic disorder resulting in multiple cysts that can alter kidney function leading to mineral imbalance and bone loss. In healthy female rats, soy protein isolate (SPI) and omega‐3 polyunsaturated fatty acids (n‐3 PUFA) increased bone mineral density (BMD), bone mineral content (BMC), and bone formation markers. The study objective was to investigate the effect of soy protein isolate and/or n‐3 PUFA supplementation on bone mass and strength in rats with PKD. Growing female pck rats (n=12/group) were randomly assigned to be fed soy protein isolate + corn oil (Casein + CO), casein + soybean oil (Casein + SO), soy protein isolate + soybean oil (SPI + SO) or soy protein isolate + 1:1 soybean/salmon oil (SPI + BLEND) for 12 wks. Urinary calcium (Ca) decreased (P=0.003) in the order of Casein + SO >; Casein +CO >; SPI +SO >; SPI + BLEND. Urinary phosphorus (P<0.001) decreased in the order of Casein + SO >; Casein CO >; SPI + BLEND >; SPI + SO. There were no significant differences in bone Ca, P, BMD and BMC among the diet groups. There were also no dietary effects on peak force, ultimate stiffness, ultimate bending stress, or young's modulus. Serum alkaline phosphatase was higher (P=0.003) in rats fed SPI + BLEND and SPI + SO compared to Casein + CO and Casein + SO. The SPI + BLEND group had the highest (P=0.001) femur length. Based on the study results, diet had little impact on the bone mass or strength of female rats with PKD.
Mushrooms not only Produce Vitamin D2 but can also Produce Vitamin D3 and Vitamin D4
Authors: Williams Jennifer , Lu Zhiren , Holick Michael F
Published: June 2021

It has been previously reported that mushrooms have the ability to produce both vitamin D2 and vitamin D4. Using high performance liquid chromatography with a photodiode ultraviolet (UV) absorbance detector we detected several vitamin Ds and provitamin Ds in mushroom samples. UV irradiated mushroom powder (Monterey Mushroom) extracted with methanol was run on a Zorbax C18 column along with standards for vitamin D2 (D2)and vitamin D3 (D3). The resulting chromatograms revealed 3 separate peaks with retention times of 11.2, 12.9 and 13.9 minutes that were similar to retention times for standards of D2, D3 and vitamin D4 (D4), respectively. Additionally, isolated pro‐vitamin D from a shitake mushroom sample was run on a Zorbax ODS column along with standards for pro‐vitamin D2 (pro‐D2; ergosterol) and provitamin D3 (pro‐D3; 7‐dehydrocholesterol). The resulting chromotograms revealed three separate peaks with retention times of 7.4, 8.2 and 8.8 minutes which were consistent with retention times for standards of pro‐D2, pro‐D3 and pro‐D4, respectively. The UV absorption spectra for D2, D3, D4, pro‐D2, pro‐D3 and pro‐D4 in the mushroom samples matched the UV absorption spectra of a 5,6‐cis triene of vitamin D and a 5,7‐diene of pro‐vitamin D standards. These results demonstrate that in addition to vitamin D2, mushrooms can also produce vitamin D3 and vitamin D4.
The MESA Program Advantage in STEM Education
Authors: Bakhiet Raga , Carcia Theresa , Alvarez Rafael
Published: June 2021

Objective

The objective of our work is to provide a model pathway to Science, Technology, Engineering and Mathematics (STEM) opportunities that students from precollege to community colleges/universities take toward achieving STEM industry positions or graduate school.

Methods

The San Diego MESA Alliance is a student success initiative built on best practices of the Mathematics, Engineering, and Science Achievement (MESA) Program and grant funds. The Alliance team provides essential academic and career development services to students who are interested in STEM fields at the precollege level and who are majoring in STEM fields at the college level. More than 1200 students on the STEM pipeline are served annually. Student support is based on ‘standards’ identified by industry representatives as critical for success. As a result of completing activities that are in line with these standards, students gain career development experience, workforce preparedness, and academic success.

Results

Students in these programs outperform their peers and standout in job/internship interviews due to their tangible excellence. Evaluation of the standards, implemented by means of student activities, proves that they are effective. The proposed outcomes of our model were either met at or in excess of 100%. These outcomes include the improvement of the retention of STEM students and increase of the number of STEM students graduating with B.S degrees

Conclusion

The San Diego MESA Alliance model pathway to (STEM) opportunities is a system that works. We recommend it for nationwide adoption in our efforts to maintain a strong STEM presence in the world.
Daily eating frequency is associated with diet quality and weight status in US adults
Authors: Shin Dayeon , Krumhar Kim , Richardson Rhonda , Song Won O.
Published: June 2021

Few studies have reported eating frequencies in relation to diet quality and weight status. Using 24h diet‐recall, anthropometric and socio‐demographic data of US adults (≥20y, n=4544 excluding pregnant/lactating women and diabetics) in NHANES 2007–8, we examined the association between daily eating frequencies (1–3, 4, 5, 6 and ≥7), diet quality (HEI 2005), and weight status (BMI ≥25). With SAS 9.3 (Cary, NC), we accounted for the complex survey design and sample weights in detecting the differences, trends and associations among the variables and/or subgroups by covariate‐adjusted logistic regressions and linear regression analyses. Mean eating frequencies were similar between men and women (5.0 and 5.3, respectively) with increasing frequencies from 20y to 65y (p<0.05). Eating frequencies were positively associated with diet quality in both genders, with some variations among age subgroups within a gender (p<0.05); and inversely associated with mean BMI and the prevalence of individuals with BMI ≥25 in women (p=0.06), but not in men. Findings from this cross‐sectional survey suggest that, although the degree of strength differs among age/gender groups, eating frequency is an indicator of diet quality and weight status in US adults.

Grant Funding Source: Nestle USA
Weight change and the matching of energy consumption and expenditure
Authors: Hand Gregory A. , Hebert James R. , Hill James O. , Blair Steven N.
Published: June 2021

We evaluated the balance of energy consumption and expenditure on body weight change over one year in 430 healthy young adults.

METHODS

Over a 14‐day measurement period activity was objectively measured (BodyMedia armband) and diet was measured by 3 random 24‐hr recalls. Change in weight was calculated as measured weight at baseline minus self‐reported weight 1 year earlier. Total daily physical activity (TDEE) was stratified as low/sedentary (LSA, <3METS) moderate/vigorous (MVPA, 3+METS). Correlational analyses were performed on weight change and TDEE, total daily energy intake (TDEI), and the two activity levels. Variables were determined per kg of weight. Analyses were adjusted for age and race.

RESULTS

Women averages: 69.1±0.9 kgs, rTDEE=35.1±0.4 kcals/kg/day (KKD). Men averages: 81.3±0.9 kgs, rTDEE=39±0.4 KKD. Correlations (*significant, **very significant) with 1 year weight change were TDEE (−.231**), TDEI (−.122*), MVPA (−.187**), and LSA (−.076, NS). Correlations with TDEI were rTDEE (.444**), MVPA (.893**) and LSA (.164*).

CONCLUSIONS

Regulation of body weight is a complex interaction of physical, psychological and environmental factors. While absolute TDEE is dependent on body mass, rTDEE and rTDEI correlated most significantly with moderate and vigorous activity. These data suggest that how energy is expended is a critical component of energy balance.
The Hyaluronan Receptor RHAMM Promotes Constrictive Artery Wall Remodeling
Authors: Ma Xue , Pearce Jeffrey D , Li Jing , Wilson David B. , English William P. , Edwards Matthew S. , Geary Randolph L.
Published: June 2021

Constrictive remodeling of the extracellular matrix (ECM) contributes significantly to restenosis after angioplasty. Hyaluronan (HA) accumulates at sites of injury where it facilitates collagen remodeling. SMCs interact with HA via specific receptor RHAMM for HA‐induced migration. We hypothesized that RHAMM may also mediate SMC‐ECM interactions that alter the extent of constrictive remodeling.

We determined the role of RHAMM in HA‐induced SMC adhesion to collagen, migration, and collagen gel contraction by blocking cell‐surface RHAMM with antibodies or by employing SMC from RHAMM −/− (rKO) mice. We then studied the impact of RHAMM on constrictive remodeling by measuring changes in artery wall geometry 1 month after carotid ligation in rKO and RHAMM+/+ (rWT) mice.

Attachment to collagen‐coated plates was enhanced by HA and inhibited by antibody blockade of RHAMM. RKO SMC also showed reduced adhesion. HA enhanced SMC contraction of collagen gels and RHAMM blockade or RHAMM gene deletion increased the extent of gel contraction even further. RHAMM also mediated constrictive artery wall remodeling in vivo, as carotid artery wall caliber was significantly greater in rKO mice after ligation. Neointimal thickening was similar but artery size (EEL area) was much larger in rKO mice. Thus, strategies to block RHAMM at sites of injury may prove useful in the prevention of clinical restenosis.
CONTRACEPTIVE AND ABORTIFACIENT EFFECTS OF LIME VAGINAL DOUCHE IN ALBINO WISTAR RATS
Authors: Bassey Rosemary Basiono , Bakare Airat Adeola , Edagha Innocent Asuquo , Peter Aniekan Imoh
Published: June 2021

Objective

To study the contraceptive and abortifacient effects of lime vaginal douche and its consequent histopathologies on reproductive organs of adult female albino Wistar rats.

Methodology

Thirty‐five adult female Wistar rats were used and five adult males kept for mating. The animals were randomly divided into groups of five animals per cage. Group 1: concentrated lime juice, group 2: 50% concentrated lime juice group 3: concentrated lime juice and mated, group 4: 50% concentrated lime juice and mated, group 5: mated then administered concentrated lime juice, group 6: mated then administered 50% lime juice and group 7: control. The lime juice was administered intra‐vaginally for 2 weeks. Vaginal smears were taken daily to study the estrous cycle. Groups 1, 2 and 7 were sacrificed after two weeks and uterus, ovary and vagina were prepared for histology; while groups 3 to 6 were sacrificed on the 21st day of gestation.

Results

Lime juice showed some contraceptive but no abortifacient effects; however the fetus were not well‐developed. There were some irregularities in the estrous cycle. In the rats administered lime juice, the uterus showed areas of inflammation and vascular congestion; the ovaries showed cortical area with lining degenerated, marked cellular degeneration, follicular degeneration, atrophy and inflammation while the vagina showed marked areas of cellular degeneration, vascular degeneration and inflammation.

Conclusion

Lime juice vaginal douche has teratogenic effects and adverse effects on female reproductive system.
Matrix Metalloproteinase Inhibition Protects Kidney from Adverse Remodeling Induced by Hypertension
Authors: Pushpakumar Sathnur , Kundu Sourav , Metreveli Naira , Tyagi Suresh C , Sen Utpal
Published: June 2021

Extracellular matrix (ECM) remodeling is the hallmark of hypertensive nephropathy. Uncontrolled proteolytic activity due to an imbalance between matrix metalloproteinases and tissue inhibitors of metalloproteinases (MMPs/TIMPs) has been implicated in renal fibrosis. We hypothesized that inhibition of MMPs will reduce excess ECM deposition and modulate autophagy to attenuate hypertension. Dahl‐salt sensitive (Dahl‐SS) and Lewis rats fed on high salt diet were treated without or with 0.5mg/mL of GM6001 (MMP inhibitor) by intra‐peritoneal injection on alternate days for 3 weeks. GM6001 treatment significantly reduced mean blood pressure in Dahl‐SS rats compared to its untreated controls. Renal ultrasound revealed increased resistive index in Dahl‐SS controls indicating vascular stiffness which improved upon treatment. Barium angiography demonstrated a reduction in terminal branches of renal vessels in Dahl‐SS controls and GM6001 treatment resulted in significant improvement. MMP inhibition reduced type‐1 collagen and increased elastin in renal vessels indicating reduced fibrosis. Untreated Dahl‐SS rats exhibited high levels of superoxide anion and decreased levels of autophagy which was mitigated by GM6001 treatment. We conclude that MMP inhibition (GM6001) reduces adverse renal remodeling in hypertension by decreasing ECM turnover and stimulating autophagy.
Septic cardiomyopathy is improved by enhancing cardiomyocyte denitrosylation capacity
Authors: Sips Patrick Yves , Zou Lin , Irie Tomoya , Nguyen Rebecca , Chao Wei , Kaneki Masao , Ichinose Fumito
Published: June 2021

Objective

to test the hypothesis that reducing cardiomyocyte protein S‐nitrosylation can improve myocardial depression associated with sepsis.

Methods and results

We generated novel transgenic mice overexpressing S‐nitrosoglutathione reductase (GSNOR), an enzyme promoting protein denitrosylation, specifically in cardiomyocytes (GSNOR‐CMTg mice). Echocardiographic measurements showed that GSNOR‐CMTg mice had a significantly improved cardiac function compared to wild‐type (WT) mice 6 hours after lipopolysaccharide (LPS) injection, while no difference was observed at baseline. Analysis of isolated heart function on a Langendorff setup confirmed a higher contractility in GSNOR‐CMTg hearts than in WT hearts after LPS. Isolated GSNOR‐CMTg cardiomyocytes showed increased cell shortening compared to WT cells after LPS, with no differences at baseline. However, we found a similar LPS‐induced depression in intracellular systolic Ca2+ transients in both genotypes. This suggests that GSNOR‐CMTg cardiomyocytes have an increased Ca2+ sensitivity after LPS. Finally, we confirmed that overexpression of GSNOR resulted in a decrease in total cardiac protein S‐nitrosylation after LPS.

Conclusion

Our results indicate that cardiomyocyte‐specific reduction of protein S‐nitrosylation protects against sepsis‐induced cardiac dysfunction, presumably by improving cardiomyocyte Ca2+ sensitivity.
Endogenously‐generated lipid peroxidation products dilate rat cerebral arteries by activating TRPA1 channels in the endothelium
Authors: Sullivan Michelle Nicole , Bruhl Allison , Earley Scott
Published: June 2021

The Ca2+‐permeable ankyrin (A) transient receptor potential (TRP) channel TRPA1 is activated by a variety of pungent and irritating electrophilic substances. TRPA1 channels are present in the cerebral artery endothelium, but physiological activators of the channel in this tissue are not known. We tested the hypothesis that lipid peroxidation products (LPP) generated by reactive oxygen species (ROS) are endogenous activators of TRPA1 in the cerebral endothelium. We found that NADPH, a substrate of the ROS‐producing enzyme NADPH oxidase (NOX), increased TRPA1 Ca2+sparklet frequency in primary cerebral artery endothelial cells (0.04 ± 0.02 Hz before vs. 0.28 ± 0.08 Hz after, n = 20–30). NADPH also dilated pressurized (80 mmHg) rat cerebral arteries in a concentration‐dependent manner (EC50 = 1.2 μM). This response was diminished by the selective TRPA1 antagonist HC‐030031 (HC) (61.3 ± 21.6% dilation (NADPH) vs. 8.7 ± 16.2% dilation (HC + NADPH), n = 3). The LPP 4‐hydroxy‐nonenal (4‐HNE) also caused cerebral artery dilation (EC50 = 8.4 μM) that was abolished by HC (51.4 ± 7.8% dilation (4‐HNE) vs. 0.0 ± 11.6 % (HC + 4‐HNE), n = 5). Immunolabeling of rat cerebral arteries demonstrates co‐localization of TRPA1, NOX2, and 4‐HNE in myoendothelial junction (MEJ) sites. Together, our findings suggest that NOX‐derived LPP dilate cerebral arteries by activating TRPA1 in MEJs. HL091905.
Angiotensin II (AngII) is rapidly metabolized in neuronal cell culture media as determined by liquid chromatography‐tandem mass spectrometry (LC MS/MS)
Authors: Basu Urmi , Madayiputhiya Nandakumar , Zimmerman Matthew C.
Published: June 2021

Previous reports using AngII‐sensitive neuronal cell culture models suggest that AngII induces chronic changes in various cell signaling proteins (e.g. kinases & transcription factors). Many of these studies stimulated cultured neurons with a single administration of exogenous AngII and harvested neurons 1–3 days later to investigate changes in protein levels. One limitation of such “chronic” AngII stimulation studies is the lack of evidence indicating the length of time exogenous AngII remains in neuronal cell culture media. Herein, using LC MS/MS, we tested the hypothesis that exogenous AngII is quickly metabolized to other angiotensin peptides in neuronal cell culture media. AngII (104.62pg/μl) was added to cultured CATH.a neurons and media was collected 15 min – 24 hr later for LC MS/MS analysis. Media levels of AngII rapidly and significantly decreased over time (52.8pg/μl AngII at 15 min; 4.2pg/ul at 3 hr; 0.37pg/μl at 24 hr, p<0.05, n = 3–4). At early time points (15 min – 3 hr), levels of AngIII and Ang1–7, two peptides generated from AngII, increased with a subsequent decrease at later times. Levels of AngI and AngIV did not significantly change. These studies provide new insight into the half‐life and metabolism of AngII in neuronal cell culture media and suggest previous studies using a single administration of AngII to study “chronic” AngII intra‐neuronal signaling pathways be reevaluated. NIH R01HL103942
The role of cGMP‐dependent nitric oxide signalling on cardiac repolarisation
Authors: Brack Kieran , Caves Rachel , Ng G. Andre , Mitcheson John
Published: June 2021

Recently, roles for nitric oxide (NO) signalling pathways have been linked with regulation of cardiac repolarisation and protection from arrhythmias. In this study, cGMP‐dependent regulation of repolarisation was investigated using BAY 60–2770, a novel NO and haem‐independent soluble guanylyl cyclase (sGC) activator. Action potentials (AP) were recorded from isolated guinea‐pig ventricular myocytes using the perforated‐patch clamp technique. Cellular cGMP was quantified by radioimmunoassay. 1 μM BAY 60–2770 increased cellular cGMP by 2.1 ± 0.2 (n=5) fold on its own, by 7.9 ± 0.7 (n=4) fold in the presence of 100 μM IBMX a non‐selective phosphodiesterase (PDE) inhibitor, and by 38.7 ± 0.2 (n=2) fold in the presence of ODQ (which strongly potentiates the action of BAY 60–2770 on sGC). Despite substantial increases in cellular cGMP, changes in AP duration were modest. BAY 60–2770 shortened AP duration from 223.3 ± 8.1 ms in basal conditions to 213.0 ± 7.4 ms (n=6, P<0.001) ms and ODQ + BAY 60–2770 caused no further shortening. Importantly, when cGMP hydrolysis was blocked by IBMX, BAY 60–2770 prolonged APs by 19.5 ± 5.6 ms (p < 0.01, n = 8). Overall, these findings demonstrate the complex interplay between cGMP and cAMP mediated effects on cardiac repolarisation. Our results further demonstrate that PDEs limit cGMP accumulation close to ion channels in the sarcolemma, thus compartmentalising cGMP signalling.

KEB is supported by a British Heart Foundation Fellowship and REC by a University of Leicester PhD studentship
Effects of Hsp27 overexpression and phosphorylation state on muscle hypertrophy and function induced by functional overload in mice
Authors: Chamney Carissa , Godar Michelle , Huey Kimberly
Published: June 2021

Functional overload (FO, removal of major synergists) induces muscle growth and increased strength and fatigue resistance. With FO, Hsp25 (rodent form of Hsp27) expression and phosphorylation is significantly increased in hypertrophying muscle suggesting its role in muscle adaptation to loading stressors. Since phosphorylation can modify stress‐related Hsp25 functions, we tested the hypothesis that overexpression of human Hsp27 (TG) or a nonphosphorylatable Hsp27 mutant (MUT) will respectively increase and decrease FO‐induced muscle growth and function vs. wild type (WT) mice. Plantaris (Plt) isometric force and fatigue were measured in vivo 14 or 30 d after FO or sham surgery. Plt mass increased ~ 2 fold with FO in all groups, but was lower in MUT than WT at 14d (p<0.05). Plt maximal isometric force was 30% lower in MUT than WT at 30d (p<0.05) and tended to be lower in TG than WT at 14 and 30d. Fatigue resistance was lower in MUT than WT at 14 and 30d (16 and 32% respectively) and 20% lower in TG than WT with Sham only (p<0.05). Results suggest that elevated Hsp27 levels do not alter muscle adaptation to FO; however, preventing Hsp27 phosphorylation attenuates adaptations in force and fatigability compared to WT with 14 or 30d of FO. This suggests Hsp27 phosphorylation dependent functions (e.g. reducing apoptosis) may be involved in processes that increase muscle strength and fatigue resistance. Funded by NIH R15AR060469
Short‐term exercise training shifts the control of sympathetic vasoconstriction in contracting skeletal muscle to the α2‐adrenergic receptor
Authors: Jendzjowsky Nicholas Gregory , DeLorey Darren Scott
Published: June 2021

We hypothesized that short‐term mild‐ (M) and heavy‐intensity (H) exercise training (ET) would augment α2‐adrenergic receptor mediated vasoconstriction in skeletal muscle. Sprague‐Dawley rats (n=30) were randomized to sedentary (S), M (20m/min5% grade) or H (40m/min5% grade) ET groups and trained 5d/wk for 4 wks with equal ET volume. Rats were anesthetised and instrumented for lumbar sympathetic chain stimulation and measurement of femoral vascular conductance (FVC). Triceps surae muscles were contracted at 60% of maximal contractile force. The percent decrease in FVC to sympathetic stimulation (2 and 5 Hz) was determined at rest and during contraction before (C) and after α2 blockade (Yohimbine; Y). ET increased (p<0.05) vasoconstrictor responsiveness. Y did not alter (p>;0.05) the decrease in FVC in S rats at rest (C: 2Hz: −22±5% 5Hz: −36±6%; Y: 2Hz: −20±5% 5Hz: −34±6%) or during contraction (C: 2Hz: −6±4% 5Hz: −18±5%; Y: 2Hz: −7±3% 5Hz: −16±5%). In contrast, Y reduced (p<0.05) vasoconstriction in ET rats at rest (M: C: 2Hz: −34±4% 5Hz: −47±7%; Y: 2Hz: −26±5% 5Hz: −38±7%; H: C: 2Hz: −44±5% 5Hz: −57±8%; Y: 2Hz: −30±6% 5Hz: −46±6%) and during contraction (M: C: 2Hz: −12±3% 5Hz: −20±3%; Y: 2Hz: −3±2% 5Hz: −11±5%; H: C: 2Hz: −12±3% 5Hz: −19±7%; Y: 2Hz: −4±3% 5Hz: −12±2%). ET increased α2 mediated constriction and shifted the control of sympathetic vasoconstriction in contracting muscle to the α2 receptor. NSERC, Canada.
Multivitamin/mineral usage, MyPlate adherence, and diet quality among college students
Authors: Tully Leah Rose , Morrell Jesse Stabile , Mastriano Christie Marie
Published: June 2021

Little is known about multivitamin/mineral supplement (MVM) usage among college students. The purpose of this study is to investigate MVM usage and its relationship to overall dietary quality. Initiated in 2005, College Health and Nutrition Assessment Survey (CHANAS) is an ongoing cross sectional survey of the health of young adults (18–24 yrs). Participants (n=4,351; 26% men) completed a 3‐day nutrient analysis and a wellness questionnaire. Dietary quality was based upon MyPlate guidelines for the average male (19 yrs; 5′8″; 174 lbs; 30–60 mins mod‐intense activity/day) and female (19 yrs; 5′4″; 139 lbs; 30–60 mins mod‐intense activity/day) participant. Subjects were separated into 4 groups according to the number of MyPlate categories they met (0, 1, 2, ≥ 3). One‐third of all students reported MVM usage. Men were more likely than women to meet MyPlate recommendations (≥ 3 categories) (23% vs. 12% p < 0.05). MVM users were more likely than non‐users to meet MyPlate recommendations (17% vs. 13% p < 0.05). Data suggests that among college students MVM usage is associated with greater MyPlate adherence. Further, college men are more likely than college women to meet MyPlate guidelines. Supported by NHAES grant NH00541.
Functionality enhancement of conventional propolis by using enzymatic lipid removal process
Authors: Park Hyein , Park Eu Ddeum , Yeon You Kyung , Lee Heeseok , Chang Un Jae , Suh Hyung Joo
Published: June 2021

Propolis, a bee product composed mainly of plant originated resins and bee wax, is one of the most popular traditional remedy for its beneficial effect on human health. However, the application of propolis on food is still limited due to its low water solubility. In this research, we treated lipase to remove bee wax from conventional propolis and consequently confirmed the safety of propolis in animal model. No adverse effect of enzyme treated PE was observed in the animal study. In the skin irritation test, neither treated lipase PE nor non‐treated lipase PE induced adverse skin reactions, such as erythema or edema. In skin sensitization, PE, Lipase OF and Lipozyme TL IM had a positive skin sensitization at the rate of 14%, 33% and 14%, respectively. Conclusively, skin safety of propolis can be enhanced by enzymatic lipid removal process.
Obesity in Mexican preschooler is associated to low physical activity and diet imbalance
Authors: Becerra Laura Beatriz Trujillo , Chávez Luis Nabor , García Olga Patricia , Anaya‐Loyola Miriam Aracely
Published: June 2021

The objective of this study was to evaluate the difference in energy expenditure and its relationship with overweight and obesity in 30 children of both sexes aged between 3 and 6 years. Weight, height, body composition and resting energy expenditure (REE) were measured. Total energy expenditure (TEE) and dietary intake were estimated by questionnaires. A total of 37% of children were overweight/obese (OW/OB) and 90% of total had elevated body fat. The difference in REE between OW/OB and normal weight children was not significant (81.6 kcal/d; P=0.1601). The average REE was 900 ± 152 kcal/d ad was significantly higher in boys (P=0.04). Mean physical activity coefficient was 2.43 MET's; 90% of children had light physical activity and 10% moderate. The mean caloric intake was 1968 ± 453 kcal/d with no difference by gender (P=0.8292). Dietary daily energy intake was above 30% of recommendation, with high percentages of proteins and lipids intake (17% and 35%, respectively). Sugars consumption represented 41% of total carbohydrate intake while dietary fiber was about 22 g/d, being 10 g higher in girls. TEE was half of dietary intake (944.8 kcal/d vs. 1968.6 kcal/d). In conclusion obesity in preschoolers correlated with both TEE and dietary macronutrient imbalance. This study was supported by FOFI‐UAQ‐ 2012.
The role of cyclin‐dependent kinase 6 in cardiac development and hypertrophy
Authors: Bryan Crystal , Blanton Robert , Aronovitz Mark , Karas Richard , Hu Miaofen , Hinds Philip W.
Published: June 2021

Heart failure affects 1–3% of people in the Western world and is strongly associated with cardiac hypertrophy. Studies have linked the cell cycle machinery to this process, but the role of cyclins and cyclin‐dependent kinases (cdks) remains poorly understood. Our research focuses on the role of the G1 cell cycle regulator cdk6 during normal development and cardiac stress. Cdk6 acts with D‐type cyclins to promote S‐phase entry in proliferating cells, but is also known to be induced concomitant with cardiac hypertrophy after transaortic constriction (TAC). Through in vivo studies utilizing cdk6 knockout (KO) mice, we observed decreased heart weight/tibia length ratios in KO mice. One objective of this project is to understand how cdk6 regulates cardiac size. Our data indicate that cdk6 is required for proper levels of proliferation and timing of differentiation of embryonic cardiomyocytes. Another objective of this project is to study the role of cdk6 in cardiac stress. Our ongoing studies suggest that cdk6 loss may impair harmful cardiac remodeling which leads to heart failure. We observe blunted hypertrophy in response to TAC in KO animals, with IL‐1β playing a key role. If this suppression of pathologic hypertrophy is accompanied by superior function following TAC, therapeutics targeting cdk6 may be indicated following cardiac injury to reduce the possibility of subsequent heart failure.