bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression patterns induced by HPV‐16 L1 VLP in leukocytes from vaccine recipients
Authors: Pinto Ligia A , Garcia‐Pineres Alfonso J , Hildesheim Allan , Dodd Lori , Kemp Troy J , Yang Jun , Fullmer Brandie , Harro Clayton , Lowy Douglas R , Schiller John T , Lempicki Richard A 
Published: June 2021

To determine the cellular pathways induced by an HPV‐16 L1 VLP vaccine, we compared the gene expression signature in L1 VLP‐stimulated PBMC from 19 vaccine and 7 placebo recipients before vaccination, and 1 month after receiving the second immunization. Cells were incubated for 72 hours with or without HPV‐16 L1 VLP before total RNA extraction. Gene expression was analyzed using the Human Genome Focus Affymetrix Array.Vaccination with HPV 16 L1 VLP was associated with a differential expression of genes in the immune/defense response, cytokine, cell signaling and cell cycle pathways in VLP‐stimulated PBMC. In addition, there was up‐regulation of genes associated with cytotoxic (GZMB, TNFSF10) and regulatory (INDO, CTLA4) activities. The strongest correlations with neutralizing antibody titers were found for cyclin d2 (CCND2) and the IL‐1 receptor antagonist (IL1RN). Twenty‐two differentially expressed genes were selected for confirmation by RT‐PCR in an independent group of 9 vaccine recipients. Agreement with the microarray data was seen for most of these genes.In conclusion, microarray technology was used to identify host gene expression profiles induced by HPV‐16 L1 VLP in leukocytes from vaccine recipients. Further studies are needed to define their potential utility in prediction of HPV vaccination outcomes in clinical trials. (Funded by N01‐CO‐12400)
Macrophages pulsed with intact Streptococcus pneumoniae play an active role as antigen‐presenting cells in eliciting an anti‐protein response upon adoptive transfer into naïve mice
Authors: Vasilevsky Sam , Colino Jesus , Canaday David H. , Snapper Clifford M 
Published: June 2021

Macrophages, in contrast to dendritic cells (DC) are regarded as ineffective for priming naïve CD4+ T cells, but the relative role of these cells in promoting T cell‐dependent humoral immunity in a naïve host is largely unknown. We isolated bone marrow‐derived (BMM) and peritoneal (PerM) macrophages, as well as bone marrow‐derived DC (BMDC) and pulsed them with intact S. pneumoniae (Pn) followed by transfer into naive WT mice. Both Pn14‐pulsed BMM and PerM, elicited an IgM and/or IgG anti‐protein and anti‐polysaccharide (PS) response comparable to that of BMDC. Whereas the IgG anti‐protein response by Pn‐pulsed BMM exhibited an absolute requirement for T cells in the recipient, the induced anti‐PS response was largely T cell‐independent. Nevertheless, in vitro, Pn‐pulsed BMDC secreted significantly more pro‐ and anti‐inflammatory cytokines, underwent a greater degree of phenotypic maturation, and presented pneumococcal surface protein A (PspA) to a PspA‐specific T hybridoma more efficiently than either BMM or PerM. Pn‐pused BMM that were paraformaldehyde‐fixed prior to transfer or lacking expression of CD40 or MHC‐II failed to elicit an anti‐protein response, although the anti‐PS response was largely unaffected. These data are the first to demonstrate that macrophages can play an active role as APCs for eliciting a protein‐specific Ig response in vivo in a naïve host.Supported by NIH grant 2R01 AI49192
CD8 T cell response to Mycobacterium tuberculosis
Authors: Einarsdottir Thorbjorg , Flynn JoAnne L 
Published: June 2021

The immune response against Mycobacterium tuberculosis (Mtb) is generally sufficient to contain, but not clear, the infection. Memory forms following Mtb infection and BCG vaccination, but doesn't protect from reinfection with Mtb and has limited effect on bacterial load. Our research is aimed at better understanding CD8 T cell responses to Mtb and identify host factors that prevent clearing of the bacteria. We created recombinant Mtb expressing OT1 and OT2 epitopes, recognized by CD8 and CD4 T cells respectively, which allows us to follow Ag‐specific cells during murine infection. Using tetramers, ELISpot, in vivo cytotoxicity assay and intracellular cytokine staining, OT1 responses were compared to responses against an endogenous Mtb epitope (from Rv0125, designated GAP).Our results indicate that memory cells reside in lung and lymph node after bacterial clearance and can respond faster than naïve cells. Despite this, the frequency of responding cells is not appreciably higher during memory response. This low frequency may contribute to inefficiency of the response. Additionally, most CD8 T cells are cytolytic (characterized by CD107 surface expression) or IFNg producers, but not both. Cytolysis and IFNg are both important in controlling Mtb, and the inabilityof CD8 T cells to perform both functions may contribute to persistence of bacteria in the host.Funding: NIH/NIAID AI37859‐10
Underweight and overweight cluster equally with child stunting in Indonesia
Authors: Doak Colleen , Baron Ruth , Ponce Maiza Campos 
Published: June 2021

Background: Previous published results showed a dual burden of underweight and overweight within households in Indonesia. Aim: This study documents the dual burden in stunted pre‐school children from Indonesia in 2000.Methods: Definitions for stunting, underweight, wasting and overweight/obesity are based on the WHO international growth standards. Maternal weight status is assessed based on BMI definitions for underweight, overweight, or normal weight.Results: Stunted children were predominantly normal weight (86.7%) whereas the prevalence of overweight (6.7%) and wasting (6.6%) were nearly equal. Furthermore, mothers of stunted children were also predominantly normal weight (69.1%) with only a slightly higher prevalence of overweight (17.2%) than underweight (13.7%). Comparing maternal under and overweight, stunted children two and under more frequently clustered together with underweight mothers. In contrast, the older children more frequently had overweight mothers.Conclusions: In 2000, stunted Indonesian children and their mothers were predominantly normal weight. Furthermore, by the age of 3, stunted children have more overweight than underweight mothers. More research is needed to understand the role of food quality and/or infectious disease to the dual burden of child under‐nutrition and overweight/obesity.
The effect of dietary lysine and genetics on lysine metabolism and growth in rainbow trout
Authors: Pomeroy Stephanie Katherine , Silverstein Jeffrey T. , Barrows Frederic T , Cleveland Beth M , Blemings Kenneth P 
Published: June 2021

Since feed cost represents about 70% of production cost, inexpensive protein alternatives are desirable replacements for fish meal. One drawback to the replacement of fish meal with soybean meal is that the latter protein source is first limiting in lysine. To investigate if different genetic lines of fish would respond differently to a lysine‐deficient (LD) diet, five families with high feed efficiency and 5 with low feed efficiency were studied. These 10 families were fed a LD, soybean meal containing, diet. The highest and lowest feed efficiency families also received a lysine‐adequate (LA) diet as a positive control. For each diet x family treatment combination, 5 replicates were used. Feed efficiency and thermal growth coefficient were greater (P<0.05) while hepatic somatic index (HSI) and ammonia excretion were lower (P<0.05) for fish fed the LA diet. There was a family effect on feed efficiency (P<0.0001) and thermal growth coefficient (P<0.0001), but not ammonia excretion, HSI, or indices of lysine catabolism. A single family had a numerically more favorable feed efficiency and thermal growth coefficient, when fed the LD diet, indicating that it may possess an enhanced genetic potential for performance when consuming lysine‐deficient, soybean meal containing diets.Support: USDA/CSREES, WV‐AFMPD
Green Leafy Vegetable Extracts Prevent Cu2+‐Induced Oxidation of Human Low Density Lipoprotein
Authors: SIM HYUN JUNG , SON CHAN WOK , LIU XI WEN , KIM MEE REE 
Published: June 2021

Objective: Oxidation of low density lipoprotein(LDL) is regarded to play an important role in the development of atherosclerosis. Green leafy vegetables contain mixed antioxidants are responsible for their health benefits, and their advantage over single antioxidant may be due to a combination of additive and/or synergistic effects. In this respect, we evaluated that the total phenol content and antioxidant activity against LDL oxidation of green leafy vegetables.Methods: Freeze‐dried green leafy vegetables were extracted with methanol. we selected the vegetables showing strong antioxiant activity based on the DPPH radical scavenging activity. The selected vegetable extracts were evaluated antioxidant action of Cu2+‐induced oxidation of human LDL. In addition, total phenol content was determined colorimetrically using Folin‐Ciocalteu reagent.Results: The extracts of vegetables expressing a strong inhibition of LDL oxidation with EC50 values of less than 100 μg/mL were angelica, dandelion, mustard leaf and water spinach, which contain high total phenolic content. Highly positive correlations between inhibition of LDL oxidation and total phenol content were observed (p<0.001).Conclusion: Based on these results, it is suggested that salad vegetables, especially angelica, dandelion, mustard leaf, could be employed as easily accessible sources of natural antioxidants, especially associated with anti‐atherosclerosis purpose.
PPAR‐gamma ligands modulate growth factor and bacteria induced cellular responses in prostate carcinoma cells
Authors: Koenig Wolfgang , Allhoff Ernst Peter , Arnold Ralf , Koenig Brigitte , Ghebremedhin Beniam , Tammer Ina , Koenig Jens Ekkehard 
Published: June 2021

Prostate carcinoma cells (PC3, LNCAP, DU145) as well as prostate hyperplasia (BPH cells) can be activated for proinflammatory mediator release and parameters of innate immunity by bacteria as well as by various growth factors. Peroxisome proliferator‐activated receptors (PPAR) are ligand activated transcription factors with antiinflammatory, antineoplastic effects on tumor cell proliferation and angiogenesis. The effect of 15d‐PGJ2, and glitazones was analyzed on various prostate carcinoma cells which were stimulated with either VEGF, EGF, HGF, IGF, TNF, SEB, C5a for 5‐ to 48 hours. As bacterial stimuli were chosen Staph. aureus (n=5) or E. coli (n=5).The release of IL‐6, IL‐8, PGE2, TGFβ was studied by Elisa, by RT‐PCR and Taqman analysis the expression of p22‐, 47‐, 67‐phox, gp91‐phox, cysteinylleukotriene receptors 1, 2, trefoil peptides (TFF1‐3), protease activated receptors (PAR1‐4), toll‐like receptors (TLR2, 4, 9), cyclooxygenase 2. We show: PPARγ‐ligands 1.) interact differently with carcinoma cells for mediator release as well as cell surface receptor expression and 2.) differences in pro‐ and antiinflammatory responses depend on the individual cell as well as the stimulus via differences in signal transduction. The results suggest a potential use of PPARγ‐ligands as adjuvant therapy of prostate carcinoma and further one has to consider the individual cell type and mode of cellular activation.
Effects of green tea on lipids, blood pressure and vasorelaxation in rats with hypercholesterolaemia‐induced hypertension
Authors: Song Liyang , Koo Marcel WL , Lau Chu‐Pak , Cheung Bernard MY 
Published: June 2021

Objective: In this study, the effects of green tea on hypercholesterolemia‐induced hypertension, vascular responses in isolated aortic rings, and serum lipid profile in rats were examined.Methods: Male Sprague‐Dawley rats were divided into 4 groups. The normal control group was fed with a normal diet while the remaining 3 groups were given a diet high in cholesterol. Two of the hypercholesterol diet treated groups were administered with green tea or tea powder solution. The treatments were given for 2, 4 or 8 weeks.Results: High cholesterol diet treatment for 2 and 4 weeks induced significantly higher total serum cholesterol level (p<0.01) and blood pressure (p<0.05). There was no increase in blood pressure in tea and tea powder treated groups when compared to the normal control group. The blood pressure of the tea leaf group, and tea powder group was significantly lowered than the disease control group at 4 weeks and 4 to 8 weeks, respectively. Tea and tea powder solutions at physiologically attainable concentrations enhanced vasorelaxation induced by physiological concentrations of acetylcholine (10−8 M ‐ 10−7 M) in rat aortic rings.Conclusions: Green tea lowered blood pressure that was increased by hypercholesterolemic diet. It decreased serum total cholesterol and prevented reduction of HDL‐cholesterol level, thus tea consumption may exert beneficial effects on the cardiovascular system.
Opposing effects of the kinin B1 and B2 receptors in LPS‐induced hypotension.
Authors: Duchene Johan , Francis Stephanie , Lecomte Florence , Stidwill Raymond , Singer Mervyn , Cayla Cecile , Bader Michael , Perretti Mauro , Ahluwalia. Amrita 
Published: June 2021

Lipopolysaccharide (LPS)‐induced hypotension is absent in kinin B1/B2 receptor double knockout mice (B1B2dKO; Cayla et al., FASEB J. 2007) however, the mechanisms of this effect are uncertain. We now show that whilst LPS (12.5 mg/kg) induced hypotension is absent at 4 h it is present at 12 h in B1B2dKO mice (n = 6, p<0.05). LPS has no effect in B1KO mice (n = 6). These differences were not due to altered [NO] since LPS‐induced increases in plasma [NO] and tissue iNOS were similar in all genotypes (n = 6). However prostaglandins (PG) PGE2 and PGF1α.were elevated at 4 h (3 and 7‐fold respectively returning to basal by 12 h) in WT mice; an effect absent in B1KO mice, and delayed (evident at 12 h but not 4 h) in B1B2dKO mice (6 and 8‐fold). This effect was due to changes in COX activity since LPSinduced changes in COX‐1/2 expression were similar in all genotypes. Absence of raised [PG] was associated with reduced vascular dysfunction in isolated resistance arteries.Our data show that absence of B1 receptor abolishes LPS‐induced hypotension; however inactivation of both B1 and B2 receptors reverse this protective effect. We propose that during sepsis, B1 receptor activation causes early and substantial pathogenic PG production; whilst B2 receptor activation inhibits this response highlighting the potential of B1 receptor blockade combined with selective B2 receptor agonism in treatment of sepsis.Supported by The Wellcome Trust
Pharmacologic Probes to Differentiate Chronic Autonomic Failure Syndromes
Authors: Goldstein David S , Holmes Courtney , Sharabi Yehonatan 
Published: June 2021

Objective: The current clinical classification of chronic autonomic failure (CAF) recognizes four primary forms—pure autonomic failure (PAF), multiple system atrophy (MSA), Parkinson disease (PD), and autoimmune autonomic ganglionopathy (AAG). We provide a pathophysiologic classification scheme, based on neuropharmacologic probes: tyramine (TYR), trimethaphan (TRI) or pentolinium (PEN), yohimbine (YOH), acetylcholine (ACh, quantitative sudomotor axon reflex test, QSART), and 6‐[18F]fluorodopamine (18F‐DA) scanning.Methods: CAF groups received i.v. TYR, TRI/PEN, YOH, or 18F‐DA or ACh by iontophoresis. Blood pressure (BP) and dihydroxyphenylglycol (DHPG) responses were measured.Results: PAF involved low cardiac 18F‐DA‐derived radioactivity and attenuated (Atten.) increments (Inc.) to TYR and YOH and decrements (Dec.) to TRI/PEN, in contrast with normal reponses in AAG and MSA. MSA involved augmented (Aug.) responses to YOH and TRI/PEN and normal (Nl.) cardiac 18F‐DA, in contrast with Atten. in PD+NOH.Conclusions: Pharmacologic probes provide a pathophysiologic classification of chronic autonomic failure that can be utilized in individual patients.
Dynamic cerebral autoregulation during passive heat stress
Authors: Low David A , Wingo Jonathan E. , Keller David M. , Davis Scott L. , Zhang Rong , Crandall Craig G 
Published: June 2021

This study tested the hypothesis that passive heating impairs cerebral autoregulation. Transfer function analysis of resting arterial blood pressure (BP) and middle cerebral artery blood velocity (MCAVmean) were conducted on 9 healthy subjects, dressed in a water‐perfused suit, under normothermic (NT) and passive heat stress (HS, Δ core temperature 1.1 ± 0.2 °C, P<0.001) conditions. Passive heating reduced MCAVmean (8 ± 8 cm•s−1, P=0.01), whilst mean arterial BP was maintained (2 ± 5 mm Hg, P=0.36). In the very low frequency range (<0.07 Hz) coherence was lower during HS compared to NT conditions (0.26 ± 0.10 vs 0.57 ± 0.13, respectively, P<0.001). Coherence was >0.5 and similar between NT and HS in the low (0.07–0.20 Hz, 0.64 ± 0.19 vs 0.59 ± 0.10, respectively, P=0.40) and high (0.20–0.35 Hz, 0.63 ± 0.19 vs 0.72 ± 0.14, respectively, P=0.12) frequency ranges. Phase was higher during HS in the low frequency range (NT: 0.55 ± 0.31 vs HS: 0.82 ± 0.17°, P=0.01), whereas it was unchanged by HS in the high frequency range (NT: −0.10 ± 0.20 vs HS: 0.12 ± 0.71°, P=0.14). Transfer gain was higher during HS in the low (NT: 1.53 ± 0.41 vs HS: 1.73 ± 0.38 cm•s −1•mmHg−1, P=0.03) and high (NT: 1.55 ± 0.55 vs HS: 2.06 ± 0.37 cm•s−1•mmHg−1, P=0.03) frequency ranges. Higher transfer function estimates of gain suggest that dynamic cerebral autoregulation is impaired during HS.Supported by NIH Grant HL‐61388 & HL‐84072
Evidence for Impaired Skeletal Muscle Contraction‐Induced Rapid Vasodilation in Aging Humans
Authors: Carlson Rick E , Kirby Brett S , Voyles Wyatt F , Dinenno Frank A 
Published: June 2021

We tested the hypothesis that aging is associated with an impaired contraction‐induced rapid vasodilation in healthy adults. Single contractions of a small muscle mass were employed to isolate the local rapid vasodilatory responses independent of systemic influences on forearm hemodynamics. We measured forearm blood flow (Doppler ultrasound) and arterial blood pressure (finapres) on a beat‐by‐beat basis, and calculated the changes in forearm vascular conductance in response to forearm contractions in 18 young (24 ± 1 yrs) and 13 older (62 ± 2 yrs) healthy subjects. Single, 1‐second dynamic forearm contractions were performed at 5, 10, 20, and 40% of the subjects’ maximal voluntary contraction (MVC). At 5% MVC, there were no significant age‐related differences in contraction‐induced forearm vasodilation. However, the peak vasodilatory responses were impaired ∼40–45% in older adults at 10, 20, and 40% MVC, as were the total vasodilatory responses (∼40–50%; all P<0.05). Additionally, the immediate vasodilation (first cardiac cycle post‐contraction) for the 20% and 40% MVC trials was also impaired ∼50% with age (P<0.05). There were no significant age‐group differences in MVC or forearm fat‐free mass. Under these experimental conditions, the blunted responses with age reflect impaired local contraction‐induced rapid vasodilation.Supported by AG‐022337, AG‐027150, HL‐087952
Backpack straps decrease upper extremity blood flow
Authors: Neuschwander Timothy , Macias Brandon , Hargens Alan 
Published: June 2021

Adults in professions such as the military, firefighting, and mountain rescue routinely carry packs loaded with 60% body weight. Backpack straps are typically situated in a region where they may compress the axillary vein, causing venous hypertension and subsequently decreasing upper extremity blood flow. We hypothesize that upper extremity macro and microvascular blood flow will decrease while wearing a loaded backpack.Eight healthy volunteers (6 men, 2 women, age range: 18 – 30 years) had the right brachial artery measured with ultrasound Doppler. Index finger pulp microvascular flow was measured using photoplethysmography. Baseline flows were measured immediately before and 10 min after donning a 12kg backpack. Baseline microvascular flow was normalized to 100%; data are presented as means±SE.After wearing the pack for 10 min, brachial artery blood flow decreased from 2.66±0.36 to 1.52±0.27 mL/s (p<0.05, paired T‐test), and index finger microvascular flow decreased from 100% to 46±6% (p<0.05, paired T‐test).Even light backpack loads such as 12kg decrease upper extremity macrovascular and microvascular blood flows and may result in a loss of fine motor control and increased fatigue. Redesigning backpack straps to prevent compression of the axillary vein about the clavicle may maintain normal blood flow.Supported by UCSD Dept. of Orthopaedic Surgery Discretionary Funds.
Impact of metallothionein deficiency on soleus muscle function following acute spinal cord injury
Authors: DeRuisseau Lara R , Recca Daniel M , Bidwell Amy J , Orosz Nadia J , Pompo Kimberly M , DeRuisseau Keith C 
Published: June 2021

Metallothioneins (Mts) are small molecular weight proteins that possess metal binding and free radical scavenging properties. Furthermore, Mt is a stress protein that likely participates in the adaptive response of skeletal muscle to stressful stimuli and is up‐regulated following acute spinal cord injury (SCI). We tested the hypothesis that loss of Mt (Mt1 and Mt2; Mt−/ −) would lead to exacerbated atrophy and contractile dysfunction of the soleus muscle following acute SCI (7 days, T9 transection) in Mt−/ − mice compared to control strain mice. Transected control strain (CT; n=5) and transected Mt−/ − (MT; n=6) mice experienced an equivalent % loss of body weight by day 7 of recovery compared to pre‐surgery weight (CT = −8.6 ± 1.6; MT = −11.6 ± 2.4). Soleus muscle mass (mg) of CT (4.3 ± 0.2) and MT (4.6 ± 0.1) groups was lower (p<0.05) than the non‐surgical control strain (NS; n=5; 5.6 ± 0.3). However, preliminary data (n=1–3/group) indicate that a lower maximal specific tension (N/cm2) is generated by the soleus in MT vs. controls (NS=23.7 ± 2.5; CT=22.1; MT 19.0 ± 0.0). In summary, deficiency of Mt1 and Mt2 does not alter the loss of muscle mass but may lead to lower maximal force generating ability of the soleus in response to disuse resulting from spinal cord injury.Supported by Syracuse University SOE
hTERT overexpression delays replicative senescence but not damage‐induced senescence of vascular endothelial cells isolated from patients with severe CAD
Authors: Voghel Guillaume , Thorin‐Trescases Nathalie , Mamarbachi Maya , Villeneuve Louis , Perrault Louis P , Carrier Michel , Thorin Eric 
Published: June 2021

Overexpression of the catalytic subunit of telomerase (hTERT) immortalizes healthy human endothelial cells (EC) but its effect on senescence in pathological conditions is unknown. Our objective was to investigate whether hTERT overexpression would prevent senescence in EC isolated from patients with coronary artery disease (CAD). EC isolated from discarded internal mammary arteries of 11 patients undergoing CABG were infected or not with a lentivirus expressing hTERT and cultured in vitro. We quantified senescence by cytochemical detection of senescence‐associated b‐galactosidase, hTERT activity by real‐time TRAPassay, telomere length by Southern blotting, mRNA levels (p21 and ATM, a DNA damage response protein) by qPCR and oxidative stress by immunostaining of lipid peroxidation (HNE). Compared to control EC, lentiviral infection increased hTERT activity (p<0.05), elongated telomeres (p<0.05), decreased ATM and p21 mRNA levels (p<0.05), increased EC replicative potential (p<0.05) but only delayed the onset of senescence (p<0.05). HNE levels increased in both groups, with time (p<0.05). In conclusion, since no immortalization was observed, we hypothesize that hTERT overexpression delays replicative senescence but cannot bypass stress‐induced senescence associated with CAD.This study was supported by the Canadian Institutes of Health Research and the Fonds de la Recherche en Santé du Québec.