bluuebunny/crossref_metadata_2025_split huggingface dataset:
BACTERIAL STRAIN‐SPECIFIC EFFECTS ON IMMUNE MARKERS IN RSV INFECTED MICE
Authors: mitmesser susan hazels , Russell William Michael , O'Mahony David , MacSharry John , Ceddia Michael , O'Mahony Liam 
Published: June 2021

BackgroundRespiratory syncytial virus (RSV) causes respiratory tract infections in infants and immunocompromised individuals and has been associated with the development of asthma.ObjectiveTo evaluate the effect of feeding Bifidobacterium longum AH1206, Bifidobacterium breve AH1205, and Lactobacillus salivarius AH102 to RSV infected mice.MethodsBALB/c mice (N=10/group) were fed 109 cfu/day B. longum AH1206, B. breve AH1205, or L. salivarius AH102 for 21 days. On day 14, mice were nasally challenged with RSV. Following infection, mice were weighed and clinically scored daily. On day 21, lungs were harvested for RSV quantification and gene expression analysis of several immune biomarkers. Infected and non‐infected, placebo fed groups served as positive (RSV+) and negative (RSV‐) controls, respectively. Mann‐Whitney t‐test was used to determine statistical differences, p<0.05.ResultsAll RSV infected mice had increases in clinical scores and lost weight post‐infection with no differences among groups. There were no differences in RSV titres or cytokine gene expression among treatments. Compared to the RSV+ control, the AH102 group showed a significantly lower increase in Foxp3 expression (p<0.05). AH1206 showed significant increases in CD86, CD127 and CD11c expression compared to the RSV‐ and RSV+ controls (all p<0.01), AH 1206 also showed a significant increase in CD3 expression compared to RSV‐ (p<0.001).ConclusionStrain‐specific differences were observed in a number of immune cell markers that could play an important role in enhancing clearance and immunity to RSV infection. The clinical relevance of these findings should be the subject of further studies.
Associations between Preterm Birth, Small For Gestational Age, and Early Neonatal Morbidity, and Cognitive Function in School‐Age Children
Authors: Christian Parul , Murray-Kolb Laura , Katz Joanne , Tielsch James , Schaefer Barbara , Cole Pamela , LeClerq Steven , Khatry Subarna K. 
Published: June 2021

The long term consequences of preterm, small for gestational age (SGA, defined as birth weight for given gestational age less than the 10th percentile of the reference), and early newborn morbidity on functional outcomes are not well described. In rural Nepal, we assessed children (n~1900) at 7–9 y of age, for whom these exposures were available at birth. The prevalence of low birth weight (LBW), preterm, and SGA was 40%, 21%, and 55%, respectively, whereas symptoms of birth asphyxia and sepsis were reported in 7% and 9% of children. At follow‐up they were tested on aspects of intellectual, executive, and motor function. In multivariable regression analyses, low birth weight was strongly associated with scores on the Universal Nonverbal Intelligence Test (UNIT), tests of executive function, and the Movement Assessment Battery for Children (MABC). However, of the two underlying causes of LBW, preterm was not associated with any of the test scores. However, SGA was significantly associated with lower UNIT scores (−1.9 SD=0.4); higher proportion failure on the Stroop test (0.06, SD=0.02); and lower scores on the backward digit span test (−0.14, SD=0.04), MABC (0.94, SD=0.27), and finger tapping test (−0.63, SD=0.23) (all p<0.005). Neither birth asphyxia nor sepsis symptoms were significantly associated with the outcomes.Support: NICHD, Gates Foundation.
Infant and young child feeding (IYCF) practices:A formative research in rural India
Authors: anwar fahmina , Srivastava Ratan , Singh S 
Published: June 2021

Exclusive Breastfeeding (EBF) & thereafter adequate complementary feeding (CF) are two important preventive interventions against child mortality. To intervene these areas, Formative research was carried out to improve Infant and young child feeding (IYCF) practises among mother & child pair of 0–6 & 7–24 months of age, in rural India. Study was conducted in 3 phases over a period of 4 months 1. Assesment: 6 Focused group discussions (FGDs) among mothers & chid pair of 0–6 & 7–24 months, 5 In‐depth interviews of Health workers & base line survey of the study village was conducted to asses perceptions & practices regarding IYCF & also to identify mothers of 0–6 & 7–24 months child. 2. egotiation: Participatory Trail for improved practices (TIPs) counselling guide with recommended practices was prepared & used to explore if mothers could try new practices & continue using them. 30 mother and child pair in each 0–6 & 7–24 months group (n =60) were selected & TIPs was tried for a period of 15 days. 3. Evaluation: To see whether new recommendations was implemented or not & what were motivating factors/barrier for same. Study revealed suboptimal IYCF practices, such as low rates of EBF, early introduction of nutrient‐poor gruels and delay in introduction of adequate CF. TIPs showed, mothers are willing to adopt new feeding practices and can increase the amount of energy & essential micronutrients like vitamin A, iron, zinc & carotene.Grant Funding Source: University Grant Commission
Breastfeeding practices and beliefs among HIV+ pregnant and lactating women on antiretroviral therapy in rural Uganda indicate obstacles to following national guidelines
Authors: Natamba Barnabas Kahiira , Robine Marion , Luwedde Flavia , Mwesigwa Julia , Natureeba Paul , Osterbauer Beth , Ades Veronica , Clark Tamara , Charlebois Edwin , Plenty Albert , Havlir Diane , Cohan Deborah , Achan Jane , Young Sera 
Published: June 2021

Ugandan guidelines recommend 6 months of exclusive breastfeeding (EBF) for HIV‐infected women on antiretroviral therapy (ART), with continued breastfeeding (BF) for at least 1 year. We explored infant feeding (IF) practices and beliefs among HIV‐infected pregnant and BF women on ART in the PROMOTE trial (NCT00993031) in Tororo, Uganda. IF practices were determined using monthly maternal reports from a prospective cohort of 219 PROMOTE infants born between March 6, 2010 and October 31, 2011 and compared to 2007 Ugandan Demographic and Health Survey (DHS) data. To assess IF beliefs, a purposive sample of 24 pregnant and 32 BF PROMOTE participants took part in in‐depth interviews (IDIs) in July and August 2011 (n=56). In the PROMOTE study, the prevalence of EBF was 90.4% and 71.6% at 3 and 6 months, vs. 64.8% and 10.8% respectively in the DHS. In contrast, the prevalence of BF at 12 months was 62.6% in PROMOTE vs. 88.3% in DHS. IDIs revealed several potential reasons for suboptimal IF: 64.3% believed that HIV was an important reason to avoid BF and 21.4% did not know the recommended duration of EBF. Of BF IDI participants, 78.1% were concerned about adequate breast milk production and 46.9% had actually experienced problems with EBF, e.g. unsatisfied baby. Among all IDI participants, 96.4% desired further IF education. Further research is needed to understand optimal support to overcome identified obstacles to BF among HIV+ women in rural Uganda.Grant Funding Source: National Institute of Child Health and Human Development
Quantifying differences in local wall stress between carotid and femoral arteries
Authors: Wang Roy , Gleason Rudy L , Brewster Luke Packard 
Published: June 2021

ObjectiveArterial remodeling after vascular procedures are mediated by pulsatile stress, but arterial wall biomechanics likely contribute; this study defines differences in arterial wall stress between healthy femoral and carotid arteries.MethodHealthy nonhuman primate arteries were tested on a custom‐made device to determine biaxial mechanical responses. A custom LABVIEW program was using for data acquisition and processing. Local wall stress was calculated based on a nonlinear, finite deformation framework utilizing an orthotropic material model. Residual stresses were considered in the analysis through quantifying circumferential and longitudinal opening angles. Heteroscedastic t‐tests were used to analyze the results.ResultsThe pressure‐diameter response of the arteries at the in vivo stretch demonstrate that femoral are stiffer than the carotid arteries (P=0.05); Fig. 1. Circumferential opening angle results (Fig. 2) also show a trend toward a greater opening angle in the femoral arteries (P=0.3).ConclusionsThese results support baseline biomechanical differences between femoral and carotid arteries in nonhuman primates. A better understanding of the matricellular differences between arteries may provide improved compatibility strategies for future therapies.(RLG:GTEC Foundation Endowment; NIH, NSF)
Expression of receptor activator of nuclear factor‐κB (RANK), RANK ligand, and osteoprotegerin in the normal and E. coli lipopolysaccharide‐treated horse lungs
Authors: Channabasappa Shankaramurthy , Singh Swaran , Singh Baljit 
Published: June 2021

Receptor activator of nuclear factor‐κB ligand (RANKL), its receptor RANK and antagonist osteoprotegerin (OPG) are members of the TNF receptor superfamily. RANKL/RANK signaling mediates TNFα‐induced inflammation and RANKL acts as a chemoattractant for immune cells. OPG interacts with and blocks RANKL signal transduction. There are no or little data on the expression of RANKL, RANK, and OPG in normal or inflamed lungs. Therefore, we studied their expression in control and lipopolysaccharide (LPS) treated horse lungs. Immunohistochemistry showed RANKL expression in alveolar/septal macrophages, vascular endothelium, and alveolar septum but not in airway epithelium in control horses. The LPS treatment increased RANKL expression in airway epithelium and alveolar septum. While a weak staining for RANK was detected in airway epithelium and vascular endothelium of control horse lungs, the expression was increased in airway epithelium of LPS‐treated horses. OPG was expressed in airway epithelium and alveolar/septal macrophages and was increased in LPS‐treated lungs. Immunoelectron microscopy detected all three molecules in pulmonary intravascular and alveolar macrophages. Western blot confirmed expression of all three molecules in the lungs. These data show LPS‐induced changes in the expression of RANK, RANKL, and OPG to suggest their roles in endotoxin‐induced lung inflammation.Grant Funding Source: NSERC
The α1A‐adrenergic receptor mediates cardiac hypertrophy through the Gαq‐PI3K‐Rac1 signaling pathway
Authors: Mohl Marion , Xiao Xiao-Hui , Balaji Poornima , Issmaa Siiri , Feneley Michael , Graham Robert 
Published: June 2021

Using a mouse model of cardiac‐specific over‐expression of the α1A‐adrenergic receptor (α1A‐AR; α1A‐M 66‐fold; α1A‐H 166‐fold) we have recently shown that acute activation of the α1A‐AR results in enhanced contraction through activation of α1A‐AR‐operated Ca2+ entry via Snapin and TRPC6.We have now defined a hypertrophic signalling pathway involving α1A‐AR‐mediated recruitment of Gαq‐PI3K‐Rac1 that is distinct from the contractile pathway. Cardiomyocytes from adult α1A‐M, α1A‐H and WT mice stimulated with the α1A‐AR‐specific agonist A61603 exhibited dose‐dependent increases in hypertrophic gene expression, protein synthesis, and cell surface area that were proportional to the level of receptor expression and were Gαq‐PI3K‐Rac1‐dependent. Inhibition of the α1A‐AR contractile pathway by blockade of TRPC6 did not inhibit α1A‐AR‐mediated induction of cardiac hypertrophy.The elucidation of two distinct α1A‐AR‐mediated signalling pathways, one increasing cardiac contraction upon acute activation and the other inducing cardiac hypertrophy upon chronic activation, identifies the α1A‐AR as a potential target for the development of pathway‐specific α1A‐AR‐agonist drugs to treat heart failure.Sponsor: NHMRC, NHF
GPCR‐mediated Modulation Of Synaptic Transmission
Authors: Betke Katherine , Rose Kristie , Friedman David , Chen Yunjia , Wang Qin , Gilsbach Ralf , Hein Lutz , Caprioli Richard , Hamm Heidi 
Published: June 2021

Synaptic transmission is characterized by exocytotic events which mediate the release of chemical transmitters to facilitate neuronal communication. GPCRs such as the α2A adrenergic receptor play an important role in controlling this process as they act as feedback regulators for transmitter release from presynaptic terminals via their G protein βγ subunits. Many current therapies targeting these receptors exhibit significant side effects, and as such, dissection of the downstream mechanisms by which they modulate exocytosis may reveal more disease‐selective targets for therapeutic intervention.Gβγ subunits have been shown to bind directly to SNARE proteins to regulate fusion events. Studies suggest unique Gβγ combinations may differentially interact with SNARE proteins to regulate exocytosis; however, no study has been able to describe the subcellular localization of isoforms to presynaptic terminals, nor link their activation to specific receptors. Utilizing synaptosome preparations and targeted mass spectrometric approaches, the current study evaluates the distribution of Gβγ subunits at presynaptic terminals expressing α2A adrenergic receptors and the physiological relevance of the Gβγ‐SNARE interaction. This work was supported by the NIH (EY010291).
Finding novel intragenic suppressors of a constitutively active allele of Gs alpha
Authors: Janevska Daniela , Din Eraj , Tobar-Rubin Raquel , Alvarez Rebecca , Chaudhry Faiza 
Published: June 2021

McCune‐Albright Syndrome (MAS) is a genetic disorder caused by mutations that inhibit GTP hydrolysis in Gsα, permanently activating the protein. We have developed a yeast model system for MAS in which mutations in the yeast Gα subunit homologous to those seen in MAS (R297H) prevent colony formation when the mutant allele is the only Gα gene present in the cells. We then constructed of a library of 32,000 secondary mutations in the constitutively active yeast Gα gene with the goal of identifying intragenic suppressors of the MAS mutation. Nine novel suppressor alleles have been identified and have been mapped to the crystal structure of the Gsαƒnprotein. Suppressor mutations have been identified in the GTP‐binding site of the protein, near the βγ‐interaction surface, on a potential effector interaction surface, in switch III, and also on regions of the α subunit with no currently characterized function. The construction of a detailed map of sites on the surface of Gα which can inactivate the MAS allele can drive rational drug discovery of better treatments for MAS patients.Funded by NIH grant 1R15ED020190‐01
Angiotensin (1–7) Antagonizes Angiotensin II Action in SHR Hypothalamic Neurons via Stimulation of PTEN Expression
Authors: Modgil Amit , O'Rourke Stephen T. , Sun Chengwen 
Published: June 2021

It was demonstrated previously that Ang (1–7) counter‐regulates Ang II action in neuronal activity of SHR neurons. However, the underlying molecular mechanisms are still not fully known. Our objective in the present study was to characterize the signal transduction mechanism of phosphatidylinositol 3‐kinase (PI3K) and phosphatase and tensin homologue deleted on chromosome ten (PTEN) involvement in the counter‐regulatory effect of Ang (1–7) on Ang II action in neurons cultured from hypothalamus of WKY vs. SH rats using current clamp recording.Application of Ang II produced a 44% greater increase in neuronal firing in SHR vs. WKY neurons. Chronic treatment with Ang (1–7) (100nM, 24 hrs) and inhibition of PI3K using lentiviral vector (LV‐DNp85α) significantly abolished Ang II mediated increase in neuronal firing rate in SHR vs. WKY neurons. Pretreatment of Ang (1–7) attenuated Ang II‐induced increase in the phosphorylation of Akt by 83% in SHR vs WKY neurons. Treatment with Ang (1–7) (100nM, 24 hrs) significantly enhanced PTEN expression in both WKY and SHR neuronal cultures using western blot and real‐time PCR. These effects of Ang (1–7) were blocked by A‐779 (10 μM), a Mas‐R antagonist. The data demonstrate that Ang (1–7) induces PTEN expression via Mas‐R, and depresses PI3K signaling via PKB/Akt pathway, which leads to a counter‐regulatory effect of Ang (1–7) on Ang II action in neuronal activity of SHR neurons.
Temporal lipid mediator profiles differ between plasma and bronchoalveolar lavage in mice exposed to tobacco smoke
Authors: Nording Malin Linder , Yang Jun , Hoang Laura , Zamora Vanessa , Uyeminami Dale , Espiritu Imelda , Pinkerton Kent E. , Hammock Bruce D. , Luria Ayala 
Published: June 2021

Patients with chronic obstructive pulmonary disease exhibit inflammation in the respiratory tract. In order to investigate temporal trends of the inflammatory response, a murine model of short‐term tobacco smoke (TS) exposure was used. Focus was on lipid mediators in the oxylipin family, i.e. oxidized fatty acids including eicosanoids of the cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP) metabolic pathways. Mice (C57Bl/6) were exposed to TS for 3, 9, and 15 hours, or filtered air (FA). Bronchoalveolar lavage fluid (BALF) and plasma samples underwent solid phase extraction followed by analysis with liquid chromatography coupled to tandem mass spectrometry. The resulting oxylipin levels were higher in plasma than in BALF, and a larger number of oxylipins was detected in plasma than in BALF (28 vs 21). Furthermore, the fraction of LOX‐derived oxylipins was the same, while the fraction of COX‐ and CYP‐derived oxylipins differed between BALF and plasma. Six of the LOX‐oxylipins in BALF, and none in plasma, were significantly increased after 9h of TS exposure correlating to a significant increase in total number of infiltrated cells (p=0.05). In conclusion, temporal oxylipin profiles may be used to assess the progression of pulmonary inflammation in mice exposed to TS.TRDRP 16KT‐0037, NIEHS Grants ES02710, P42 ES04699, and the Swedish Research Councils VR, Formas, and Vinnova supported this work.
Inhibition of soluble epoxide hydrolase in mice exposed to tobacco smoke
Authors: Nording Malin Linder , Yang Jun , Hoang Laura , Zamora Vanessa , Uyeminami Dale , Espiritu Imelda , Pinkerton Kent E. , Hammock Bruce D. , Luria Ayala 
Published: June 2021

Patients with chronic obstructive pulmonary disease exhibit inflammation in the respiratory tract. Epoxyeicosatrienoic acids (EETs) possess promising anti‐inflammatory properties. Hence, stabilization of EETs through inhibition of the enzyme soluble epoxide hydrolase (sEH) by small molecule inhibitors (sEHI) was investigated in a murine model of short‐term tobacco smoke (TS) exposure. Wild‐type (WT), and sEH knock out (KO) mice were exposed to filtered air (FA) or TS for 9 hours. Bronchoalveolar lavage fluid samples underwent solid phase extraction followed by liquid chromatography coupled to tandem mass spectrometry to facilitate quantitation of EETs, and their corresponding diols (DHETs) derived from arachidonic acid, as well as linoleic acid epoxides (EpOMEs), and diols (DiHOMEs). The total number of infiltrated cells was decreased in TS exposed KO mice, as well as in sEHI‐treated WT mice, compared to non‐treated mice exposed to TS. Both the EET/DHET ratio, and the EpOME/DiHOME ratio were increased in TS‐exposed WT mice treated with sEHI, compared to non‐treated mice exposed to TS. The ratios were further increased in KO mice, both exposed to TS and FA. Our results suggest that inhibition of sEH stabilizes EETs and EpOMEs, with potential beneficial effects in TS exposed mice.TRDRP 16KT‐0037, NIEHS Grants ES02710, P42 ES04699, and the Swedish Research Councils VR, Formas, and Vinnova supported this work.
The African clawed frog (Xenopus laevis) is sensitive to pyrene exposure during early development
Authors: Snoke Deena B. , Rosato Kaitlyn E. , Richardson Elizabeth M. , Whittemore Susan L. 
Published: June 2021

Toxicity of pyrene, a tetracyclic polyaromatic hydrocarbon (PAH), is poorly understood. Pyrene deposition in air, soil, and water results primarily from fossil fuel combustion. Pyrene is also abundant in cigarette smoke. PAHs cross the placenta; urinary 1‐hydroxypyrene (1‐HP) levels, a measure of PAH (and pyrene) exposure, are higher in pregnant smokers and their newborns than in nonsmokers and their newborns. Children in urban and industrial settings excrete more 1‐HP than those from rural areas. It is clear that developing humans are exposed to PAHs, including pyrene, both in utero and postnatally. To better understand how this abundant contaminant may affect development, we exposed the embryos of X. laevis, an important model of vertebrate development, to pyrene. Exposure to 5–10 ppm (25–49 μM) pyrene from stage 10.5–42 (~96 hrs) resulted in 90–100% mortality 48 hrs after their return to control conditions, while exposure to 0.1–1 ppm had no effect. Pyrene‐induced mortality may be stage‐specific. We observed 30% mortality in embryos exposed to 5 ppm until stage 18, a rate in contrast to the 90–100% mortality of embryos exposed to stage 24 or beyond. In addition, pyrene exposure induced edema at all doses (0.1–10 ppm). Based on these findings, further characterization of the toxicity of this common pollutant is warranted and potential health risks to humans assessed.(Supported by NH‐INBRE grant 1P20RR030360‐01)
The role of protease‐activated receptor‐4 in vascular smooth muscle cell migration and proliferation
Authors: Epperson Tenille , Weekes Danielle , Tillery Lakeisha , Mantey Jane , Austin Anita , Motley-Johnson Evangeline 
Published: June 2021

Recent studies have shown that thrombin stimulates the activation of extracellular regulated kinase (ERK1/2) and Rho/Rho kinase, which are associated with cellular proliferation and migration in vascular diseases such as hypertrophy and atherosclerosis. Thrombin activates these kinases through protease‐activated receptors (PARs), which are a family of G‐protein coupled receptors activated by the enzymatic cleavage of the extracellular NH2 terminus. After verifying that PAR‐4 was expressed in vascular smooth muscle cells (VSMCs), we used a PAR‐4 activating peptide (AYPGKF) to stimulate the cells in a time‐ and concentration‐dependent manner. Using Western blot analysis, we observed that 25uM of the PAR‐4 agonist maximally phosphorylated ERK1/2 at a time point of 15 minutes. To determine if PAR‐4‐induced phosphorylation of ERK1/2 was dependent on Rho kinase, we pretreated VSMCs with 25uM of the Rho kinase inhibitor (Y27632) for one hour and then stimulated the cells with 25uM of AYPGKF for 15 minutes or 5U/ml of thrombin for 5 minutes. ERK1/2 phosphorylation was significantly attenuated in the presence of the Rho kinase inhibitor when stimulated with PAR‐4. In addition, pretreatment with the rho kinase inhibitor significantly decreased thrombin‐induced ERK1/2 phosphorylation. We demonstrated that PAR‐4 signals via Rho kinase in the phosphorylation of ERK1/2. We conclude that PAR‐4 may be a key mediator in the cellular migration and/or proliferation of VSMCs.NIH‐NIGMS‐SCORE