bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure and Function of Human Senescence Marker Protein 30 (SMP30), Understanding the Zinc Dependent Gluconolactonase Activity and Calcium Regulation
Authors: Chakraborti Subhendu , Bahnson Brian J 
Published: June 2021

Senescence Marker Protein 30 (SMP30) is a 34‐kDa protein whose expression in liver, kidney and lungs decreases, with aging. SMP30 has been identified as a zinc dependent gluconolactonase, which hydrolyses various aldonolactones. The lactonase reaction with L‐gulono‐γ‐lactone is the penultimate step in Vitamin‐C biosynthesis and SMP30 knockout mice are prone to scurvy. SMP30 is also known as regucalcin, which plays a major role in intracellular calcium homeostasis. There is no reported crystal structure of this enzyme. We believe that a structure will aid in elucidating the unresolved functions of SMP30. Human SMP30 was cloned, over‐expressed and pure active protein was crystallized. The crystals diffract to < 2.0 Angstrom. We have also obtained selenomethionine protein crystals, to solve the phases. We are performing group specific labeling and site‐directed mutagenesis in order to characterize the active site. The crystal structure will complement this approach. Enzymatic assays of gluconolactonase have shown interesting metal ion behavior. Although the highest activity was observed with Zn2+, we have also observed activity with Ca2+. The use of chelating agents like EGTA/EDTA, dyes like Quin‐2, Terbium binding assays, CD spectroscopy and ITC will further characterize the role of Ca2+ in SMP30 structure and function.In the long term, our studies will reveal its overall physiological function.
Thrombin mediated regulation of CCN1 regulates cell proliferation in an integrin dependent manner
Authors: Walsh Colin T. , Hsiao Albert , Stupack Dwayne , Brown Joan Heller 
Published: June 2021

We previously reported that PAR1 (activated by thrombin) and the M3 muscarinic (activated by carbachol) receptors differentially effect AP‐1 mediated gene expression and DNA synthesis in 1321N1 astroglial cells. Microarray experiments were used to explore genes that were differently regulated by thrombin verses carbachol and revealed that the secreted protein cysteine‐rich 61 (Cyr61/CCN1) was robustly and selectively induced by thrombin. Thrombin but not carbachol activate RhoA therefore we postulated that Rho signaling mediates CCN1 expression. This was supported by experiments demonstrating that the C3 exoenzyme attenuates thrombin‐induced CCN1 expression and that other GPCR agonists that activate Rho also induce CCN1 expression while Gq coupled receptor agonists do not. Inhibition of CCN1 expression with siRNA decreased thrombin‐stimulated DNA synthesis by ~50% implicating CCN1 signaling in thrombin mediated proliferation. Currently integrins are the only known receptor for CCN1. Data shows that CCN1 is present on the cell surface of 1321N1 cells, that 1321N1 cells bind to CCN1 in an α6β1, α5β1, and β1 integrin dependent manner, and that functional inhibitory antibodies to these integrins attenuate thrombin mediated DNA synthesis. We suggest that CCN1 represents an intermediate by which G12/13 and Rho coupled GPCRs utilize integrins to elicit additional signals involved in cell proliferation.NIH 5R01‐GM36927
N‐terminal trimer extension of nominal CD8 T cell epitopes is sufficient to promote cross‐presentation to cognate CD8 T cells in vivo
Authors: Wei Cheng‐Hong , Sherman Linda A 
Published: June 2021

Cross‐presentation pathway is essential for generating effective CD8 T cell responses against cell‐associated antigens derived from either infectious pathogens or malignant cells. In this study, we investigated the regulation of cross‐presentation pathway through manipulation of the CD8 T cell epitopes using TCR transgenic mice as model system. Previous studies have shown that nominal peptide is inefficiently cross‐presented and that proteins and large polypeptides that require proteasomal processing are the main source of naturally cross‐presented antigens. Here we show that N‐terminal extension of nominal peptide by as few as three residues is sufficient to produce a substrate for TAP dependent cross‐presentation that is highly efficient in cross‐priming murine CD8 T cells in vivo. On a molar basis, cross‐priming with trimer extended peptide is 20 fold more efficient than priming with intact protein. Depending on the presence or absence of inflammatory signals, this method can lead to immunity or tolerance. Moreover, cross‐presentation of N‐terminal modified CD8 epitopes derived from insulin can significantly protect NOD mice from developing type I diabetes. Therefore, this method of peptide extension should prove of great value in facilitating in vivo studies of CD8 immunity and tolerance that rely on cross‐presentation.(This work was supported by NIH grants DK50824 and U19 AI050864)
Dendritic cells transduced with lentiviral vectors expressing vasoactive intestinal peptide (VIP) differentiate into tolerogenic‐like DC
Authors: Toscano Miguel Garcia , Ganea Doina 
Published: June 2021

It is of increased interest to generate DC with efficient and stable genetic modifications, i.e. expressing a protein with therapeutic effects, to be used as therapeutic tools. Previous results from our laboratory indicated that the neuropeptide VIP has both preventive and therapeutic effects in models of autoimmune diseases such as rheumatoid arthritis and experimental autoimmune encephalomyelitis. We had previously shown that the therapeutic effects of VIP are mediated largely through effects on DC, specifically on the generation of tolerogenic DC. However, direct treatment of human subjects with VIP could lead to significant side effects due to its action on both the cardiovascular system and gastrointestinal tract. Therefore, we used lentiviral vectors carrying the cDNA of human VIP for the transduction of DC during their differentiation from bone marrow cells. Mouse bone marrow DC were efficiently transduced by lentiviral vectors carrying eGFP (up to 60% of cells with an MOI of 10). Use of the same vectors carrying h‐VIP led to a DC population expressing close to 350 pg/ml of VIP. The VIP expressed by transduced DC acted in an autocrine manner; leading to the differentiation of tolerogenic‐like DC, characterized by a reduction in the costimulatory molecules CD40 and CD86 following LPS stimulation. In addition, we observed a downregulation in the production in the pro‐inflammatory cytokines IL‐6 and TNF‐a and an increase in IL‐10 (anti‐inflammatory cytokine).This work was supported by NIH/NIAID R01AI052306
Energy expenditure and physical activity in recovering malnourished infants
Authors: Rising Russell 
Published: June 2021

Background: Malnourished infants are small for age and weight.Objectives: Determine 24‐hour energy expenditure (24‐h EE) and physical activity (PA) in recovering malnourished infants.Methods: 10 malnourished infants (58.1 ± 5.9 cm, 7.7 ± 5.0 months), six classified as primary and four as primary/secondary, were determined to be healthy prior to spending 24‐hours in the Enhanced Metabolic Testing Activity Chamber for measurement of EE, resting (RMR) and sleeping metabolic rates (SMR), respiratory quotient (RQ; VCO2/VO2) and PA (oscillations in wt/min/kg BW). Energy intake and percent sleep were recorded. These data were compared to similar results from 10 healthy infant controls (68.8 ± 2.8 cm, 5.0 ± 0.8 months). Data analysis (SPSS, Version 13) involved independent t‐test (p<0.05) between malnourished and healthy controls and expressed as kcal/kg/day.Results: In comparison to controls, malnourished infants were lighter (4.1 ± 1.2 vs. 7.3 ± 0.8 kg; p<0.05) and had a lower BMI (12.0 ± 1.7 vs. 15.5 ± 1.5; p<0.05). In contrast, malnourished infants had greater energy intake (142.7 ± 14.6 vs. 85.1 ± 25.8; p<0.05) with a greater percentage of carbohydrates (55.1 ± 3.9 vs. 47.2 ± 5.2; p<0.05). However, malnourished infants had greater 24‐h EE (101.3 ± 20.1 vs. 78.6 ± 8.4; p<0.05), RMR (90.9 ± 18.4 vs. 66.0 ± 3.5; p<0.05), SMR (92.6 ± 17.1 vs. 65.0 ± 3.9; p<0.05) and RQ (1.00 ± 0.13 vs. 0.86 ± 0.08; p<0.05). Moreover, malnourished infants also slept more (57.2 ± 6.8 vs. 49.7 ± 6.0 %; p<0.05) and had a lower amount of PA (2.3 ± 0.94 vs. 4.0 ± 1.5; p<0.05) in comparison to controls. Moreover, malnourished infants lacked a metabolic circadian rhythm.Conclusion: Malnourished infants require more energy, possibly for growth. Moreover, it appears they conserve energy by a reduction in PA, greater amount of sleep and the elimination of the metabolic circadian rhythm.
Development of a Body Fat Prediction Equation for Young Adults
Authors: Zanovec Michael , Tuuri Georgianna 
Published: June 2021

Given the rising prevalence of obesity, particularly in young adults, it is important to develop valid field‐based methods that can used to estimate body fatness. Body mass index (BMI; in kg/m2) is currently used to categorize obesity, despite the fact that BMI is only moderately correlated with percent body fat. The purpose of this study was to develop a body fat prediction equation specifically for a college‐aged population. 270 Caucasian (n=161) and African American (n=109) students aged 18‐24 volunteered to participate. Height and weight were measured and BMI values calculated. Total percent body fat (%BF) was estimated using dual‐energy X‐ray absorptiometry (DXA). Stepwise multiple linear regression examined significant predictor variables of %BF, including gender, race, age, and BMI. The predicted residual error sum of squares (PRESS) statistic cross‐validated the model. The reduced model explained 80% of the variance in total percent body fat (%BF = 1.53[BMI] ‐ 16.47[gender] ‐ 1.29[race] ‐ 4.5; note: 0 =female, 1=male; 0=Caucasian, 1=African American). Additionally, the root mean squared error (RMSE) for the model (4.2 %BF) was equivalent to the cross‐validation statistic. These results suggest that body adiposity can be predicted with greater accuracy in a college‐aged population when gender and race are included in addition to BMI.Grant Funding Source: N/A
Modulation of heart rate variability by dietary carbohydrate in healthy adolescent African‐Americans
Authors: Austin Rachel E. , Bond Vernon , Polk Octavius D. , Millis Richard M. 
Published: June 2021

Low heart rate variability (HRV) after eating may be a risk factor for obesity among African‐Americans because of its association with a limitation of postprandial sympathetic regulation of adipokinesis and fat utilization.PurposeThe present study was designed to test the hypothesis that a subpopulation of adolescents may be differentiated by changes in HRV after ingesting beverages of high carbohydrate or high fat content.MethodsHRV was computed as the standard deviation of the normal‐normal (SDNN) and as the very low, low and high frequency spectral powers measured on electrocardiogram (ECG) RR intervals during paced breathing. Respiratory exchange ratio (RQ) and metabolic energy expenditure were measured.ResultsThe results showed that RQ consistently increased after ingestion of the high carbohydrate and did not change consistently after ingestion of the high fat beverages. The peak increment in RQ was associated with an increase in the very low frequency and a decrement in the high frequency in the absence of consistent changes in the low frequency ECG spectral power.ConclusionThese findings suggest that ingestion of high‐carbohydrate may produce sympathetic modulation of metabolism and thermogenesis in healthy adolescent African‐Americans. Furthermore, carbohydrate induced production of carbon dioxide may function as a metabolic signal for autonomic nervous system activity and HRV. The results of this study suggest that the increment in very low frequency ECG spectral power associated with ingestion of carbohydrate may be a physiological marker for postprandial sympathetic mediated adipokinesis, a limitation of which could be a marker of increased risk for obesity.
The effect of consuming pistachios on the high‐density lipoprotein (HDL) concentration of lutein and zeaxanthin (L/Z)
Authors: Radcliffe John , DiMarco Nancy , Imrhan Victorine , Grubesic Ruth , Hernandez Ladia 
Published: June 2021

HDLs play a key role in the transport of L/Z into the retina. Retinal L/Z, which reflects serum L/Z concentration, may protect against age‐related macular degeneration (AMD). Pistachios are a dietary source of L/Z, and consumption of these nuts may beneficially affect L/Z status. The effect of consumption of pistachios (68 g per day) on HDL‐L/Z was investigated in a 6‐wk feeding study with healthy adult volunteers (17 female, 13 male; mean age 38 yr) randomized into a control (n = 14) and an intervention group (n = 16). Both groups consumed their usual diets for the first two weeks of the study; for the next 4 weeks, the control group consumed their usual diets, and the intervention group was given pistachios to incorporate into their diets. HDL‐L/Z decreased by 4% for the control group but increased 52% for the intervention group; similar changes were noted for the TC‐L/Z (−1% for the control group and +53% for the intervention group). Thus, consumption of pistachios may be useful in protecting against AMD, the leading cause of blindness in adults over 65 years of age in the U.S.Funding: TWU Human Nutrition Fund; Texas Dept. of Agriculture
Ionizing Radiation Modulates Hsp34 and beta‐Catenin
Authors: Rafiee Parvaneh , Nelson Victoria , Baker John , Otterson Mary , Binion David , Shaker Reza 
Published: June 2021

INTRODUCTION: There is limited data on the effect of excess radiation on the esophagus, with the majority of data derived from radiation therapy. Heat shock protein 34 (Hsp34) protects cells against oxidative injuries. The beta‐catenin/Wnt signaling pathway is responsible for many cellular processes including cell proliferation and survival. The aim of this study was to determine the effect of irradiation on the esophagus in a rat model, focusing on epithelial expression of Hsp34 and beta‐catenin/Wnt signaling.METHODS: 35 days old male WAG/RijMCW strain of rats (n=10) were exposed to 10 Gy whole body radiation, and then received bone marrow transplant. The 2nd group of rats (n=10) served as a control (no radiation). Tissues were analyzed by immuno‐histochemistry, ELISA, RT‐PCR and Western blotting.RESULTS: Irradiated rats weighed 20% less than controls. One rat had a tumor of unknown origin with liver metastasis, 4 had severe diarrhea and one had peritoneal fibrosis. Immunohistochemical and molecular analysis of radiated rat esophageal tissue demonstrated: 1) Up regulation of Hsp34 expression. 2) Nuclear translocation of beta‐catenin. 3) Increased level of IL‐6 and COX‐2 expression and elevated levels of PGE2. 4) Increased NFkB activity. (p<0.05 for all).CONCULSION: Whole body irradiation resulted in deterioration of free radical scavenging capabilities and esophageal cellular homeostasis.
From 1997–2006: Placental Risk Factors for Stillbirth in the Bronx, NY
Authors: McLemore Michael Steven , Pal Somnath , Reznik Sandra E. 
Published: June 2021

Background: Stillbirth afflicts low‐income, minority women. We reported that stillbirths with chorioamnionitis (CA) increased in incidence at Montefiore Medical Center (MMC) from 1995–2006 (EB 2007). To date no study has compared these factors in cases to those of live births in the Bronx.Objective: To determine which factors are tied to stillbirth.Design: Stillbirth autopsies (n=150) at MMC from 1997–2006 were compared to records of randomly selected live‐birth controls (n=300).Results: The stillbirth cases were 49.7% Hispanic, 35.2% Black; controls were 41.4% Hispanic, 38.0% Black. Stillbirths had a greater incidence of CA (19.7% v. 1.3%, Fisher's Exact, p<0.0001); the odds (OR) were strong that stillbirths were linked to CA (OR=18.16, 95% CI=6.24–52.97). The incidence of advanced maternal age (AMA) was greater among cases (24.2% v. 12.0%, p=0.00095), & the odds of their tie to AMA were strong (OR=2.34, CI=1.40–3.90). The incidences of placental abruption (10.6% v. 2.0%, p=0.00018) & hemorrhage (20.4% v. 2.0%, p<0.0001) were greater among cases; the odds of a link between stillbirth & abruption (OR=5.79, CI=2.20–15.26) or hemorrhage (OR=12.58, CI=5.09–31.10) were strong.Conclusion: These findings link stillbirth to risks in the Bronx. CA disrupts amnion integrity, & abruption incites ischemia in placental & fetal tissues. These results can guide prenatal care in low‐income areas.
Fetal Risk Factors for Intra‐Uterine Demise (IUFD) in the Bronx, NY from 1997–2006
Authors: McLemore Michael Steven , Pal Somnath , Reznik Sandra E. 
Published: June 2021

Background: IUFD greatly impacts low‐income, minority women in the Bronx. We reported that IUFD cases with chorioamnionitis (CA) increased at Montefiore Medical Center (MMC) over the last 12 years (EB 2007). To date, no study has compared fetal risks in cases to those of live deliveries.Objective: To determine which factors are tied to IUFD in the Bronx.Design: IUFD autopsies (n=150) from 1997–2006 at MMC were compared to randomly selected live‐birth controls (n=300).Results: IUFDs were 49.7% Hispanic, 35.2% Black; controls were 41.4% Hispanic, 38.0% Black. IUFDs had a greater incidence of small fetal weight for gestational age (7.4% v. 0.67%, Fisher's Exact, p=0.00016). The odds (OR) were strong that IUFD was tied to small fetal weight (OR=11.88, 95% CI=2.60−54.31). The incidence of oligohydramnios was greater in cases (10.2% v. 0.67%, p=0.0065), & the odds showed this was linked to IUFD (OR=2.99, 95%CI=1.34−6.68). The incidence of polyhydramnios was greater in IUFDs (4.1% v. 0%, p=0.0012), & the incidence of hydrops was greater too (6% v. 0%, p=0.000043).Conclusion: The associations of fetal risks & IUFD are evident in the Bronx. Small fetal weight indicates vascular compromise to fetal tissues. Oligohydramnios signifies abnormal fetal genitourinary function, & polyhydramnios suggests gastrointestinal obstruction. These findings can guide prenatal care & monitoring for low‐income women.
Mosaicism for a postzygotic AVPR2 mutation resulting in partial nephrogenic diabetes insipidus
Authors: Kvistgaard Helene , Christensen Jane Hvarregaard , Roubicek Martin , Arriazu Maria Cristina , Isaac Gabriel B , Rittig Søren 
Published: June 2021

The objective of the study was to determine the genotype of a male patient diagnosed with a partial form of nephrogenic diabetes insipidus (NDI), a disorder characterized by renal tubular unresponsiveness to the antidiuretic hormone arginine‐vasopressin (AVP) and consequently excessive water secretion.Direct sequencing of the arginine vasopressin receptor 2 (AVPR2) gene on the X‐chromosome identified a heterozygous pattern for a point mutation (g.797G>A) in exon 2 predicting G122D amino acid substitution. Contamination was excluded by analysis of a new blood sample. Restriction enzyme analysis confirmed the results. Karyotyping excluded Klinefelter's syndrome (46, XY). No other mutations were found in the coding region of the AVPR2 or the aquaporin‐2 genes. Healthy family members were all homo‐ or hemizygous for the wildtype AVPR2 gene.The identified mutation has previously been reported as causing NDI. We conclude that this unusual finding of a heterozygous pattern in a male patient with an X‐linked disease must be due to a mosaic pattern of the AVPR2 gene as a consequence of a postzygotic mutation, the result being a partial NDI phenotype.Research Support: Novo Nordisk Foundation, Karen Elise Jensen Foundation.
Estradiol regulates the expression of renal sodium transporters in ovariectomized rats
Authors: Heo Nam Ju , Kim Se Joong , Oh Yun Kyu , Na Ki Young , Joo Kwon Wook , Han Jin Suk 
Published: June 2021

Although recent studies suggest that estrogen may alter renal expression of certain sodium transporters, conflicting results make its effects on the regulation of renal sodium transporters complicated. To determine the effect of estrogen on the expression of major sodium transporters, we performed semiquantitative immunoblotting analysis of the kidneys from ovariectomized (OVX) Sprague‐Dawley rats treated with (n=6) or without (n=5) high dose of 17β‐estradiol benzoate (E2) (14mcg/100g BW) for 10 days. Physiologic data including body weight (BW), blood pressure (BP), fractional excretion of sodium (FENa) and plasma aldosterone level were also measured.BP showed no difference between two groups. BW was 278 ± 20 g in E2‐replaced rats and 311 ±15 g in OVX rats(p=0.028). FENa of the E2‐replaced rats increased without significant difference (E2 vs. OVX, 0.57 ± 0.22% vs. 0.36 ± 0.19%; mean ± SD, p=0.14). Plasma aldosterone level was 179 ± 125 pg/ml in E2‐replaced rats and 315 ± 218 pg/ml in OVX rats(p=0.20). Administration of E2 led to significant decrease in the protein abundances for Na‐Cl cotransporter, Na‐K‐2Cl cotransporter, the Na‐K‐ATPase, α‐ and γ‐subunits of ENaC in the OVX rats (66%, 32%, 52%, 59% and 49% of control, respectively; p<0.05).E2 replacement to OVX rats resulted in down‐regulation of major renal sodium transporters, which might be associated with reduced plasma aldosterone level.
Activation of 5‐hydroxytryptamine type 3 receptor‐expressing C‐fiber vagal afferents inhibits retrotrapezoid nucleus chemoreceptors in rats
Authors: Moreira Thiago S , Takakura Ana C , Guyenet Patrice G 
Published: June 2021

Retrotrapezoid nucleus (RTN) chemoreceptors are regulated by inputs from the carotid bodies (CB) and from pulmonary mechanoreceptors. Here we tested whether RTN neurons are influenced by 5‐hydroxytryptamine type 3 receptor‐expressing C‐fiber vagal afferents. In urethane‐anesthetized rats, selective activation of vagal C‐fiber afferents by phenylbiguanide (PBG) eliminated the phrenic nerve discharge (PND) and inhibited RTN neurons (n = 24). PBG had no inhibitory effect in vagotomized rats. Muscimol injection into the solitary tract nucleus, commissural part, reduced inhibition of PND and RTN by PBG (73%), blocked activation of PND and RTN by CB stimulation (cyanide) but had no effect on inhibition of PND and RTN by lung inflation. Bilateral injections of muscimol into interstitial NTS reduced the inhibition of PND and RTN by PBG (53%), blocked the inhibitory effects of lung inflation but did not change the activation of PND and RTN neurons by CB stimulation. PBG and lung inflation activated post‐inspiratory neurons located within the rostral ventral respiratory group (rVRG) and inhibited inspiratory and expiratory neurons. Bilateral injections of muscimol into rVRG eliminated PND and partially decreased RTN neuron inhibition by PBG (32%). In conclusion, activation of cardiopulmonary C‐fiber afferents inhibits the activity of RTN chemoreceptors. The pathway relays within a broad medial region of the NTS and involves the rVRG to a limited degree. The apnea triggered by activation of cardiopulmonary C‐fiber afferents may be due in part to a reduction of the activity of RTN chemoreceptors.Supported by: HL 74011 (PGG) & Capes‐BEX 4402/05‐7 (ACT).