bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real‐time dynamics of pre‐mRNA transcription and splicing
Authors: Carmo‐Fonseca Maria 
Published: June 2021

The spliceosome is a dynamic RNA‐protein macromolecular machine that is responsible for the splicing of intronic sequences from pre‐mRNA. The spliceosome undergoes major structural changes during the splicing reaction and its components must be recycled for each new round of splicing. Although the spliceosome cycle has been extensively studied at the molecular level, little is known about the dynamics of splicing and spliceosome assembly in living cells.We have been using Photobleaching and Photoactivation microscopy techniques to study how splicing factors are recruited to nascent transcripts in the living cell nucleus. Currently, we are developing tools to visualize in real‐time the dynamics of RNA Pol II transcription, splicing and spliceosome assembly.
Survey of biological active molecule in the Chinese herbal formula‐ Suan Zao Ren Tang in treating insomnia
Authors: Chuang Gloria , Mao Sena , Tam W , Tam G , Tam Chick 
Published: June 2021

ObjectiveIdentify biological active molecules found in ancient Chinese herbal formula Suan Zao Ren Tang (SZRT) in treating insomnia.MethodsUse various sources of textbooks, e.g., Handbook of Active Constituents from Chinese Materia Medica & Phytomedicine (ISBN: 9620731549) by Y. H. Wing and X. P. Gen, peer‐reviewed journals, clinical studies and internet research to identify biological molecules found in the SZRT.ResultThe main herbs of Suan Zao Ren Tang are Sour Jujube Seed or Suan Zao Ren (semen Zizyphi spinosae), Fu‐Ling (sclerotium Poriae cocos) and licorice (Glycyrrhiza glabra). The active molecules found in these herbs for example are triterpene saponins , tumulosic acid and glycyrrhetic acid which are molecules important to treat people suffered from insomnia, restlessness and chronic fatigue without significant side effects of Western medications.ConclusionThe biologic active molecules found in SZRT can help people suffered from insomnia. The use of SZRT can reduce the cost when compared to the use of Western medicine, and minimize side effects of the prescriptive medication. Thus it could promote overall patients' quality of life.
Impacts of Piglet Age and Route of Delivery on Ileal Lactobacillus Diversity
Authors: Chen Long , Monaco Marcia H , Wang Mei , Donovan Sharon M , Miller Michael J 
Published: June 2021

Lactobacilli are inhabitants of the human and porcine gastrointestinal tract. Herein, Lactobacillus diversity in piglets that were either Cesarean ‐ (CD, n = 11) or vaginally delivered (VD, n=9) was characterized. Piglets were weaned on d21 and samples obtained on d3, 14, 21 and 28. Total lactobacilli increased from d3 to 14, were stable until d21 and decreased at d28. Ten random isolates per piglet were identified by partial (499‐bp) hsp60 gene sequencing using Lactobacillus specific primers and 7 species were identified: L. johnsonii, L. thermotolerans, L. reurteri, L. amylovorus, L. delbrueckii, L. salivarius and L. vaginalis. At d3, VD and CD piglets had 3‐5 Lactobacillus species, but the composition differed between the groups. At d14 and 21, L. johnsonii dominated in both CD and VD piglets (>75%). At 28 days, L. johnsonii remained dominant with VD (91%) piglets, whereas CD piglets had both L. johnsonii (72%) and L. thermotolerans (21%). Carbohydrate utilization profiles of 200 Lactobacillus isolates demonstrated intraspecies diversity confirming that several strains may be present for each Lactobacillus species. Terminal restriction fragment length polymorphism patterns (T‐RFLP) generated from ileal contents confirmed the Lactobacillus species composition identified by cultivation. Thus, piglet age and route of delivery impacts the ileal Lactobacillus community. (BMS Freedom to Discover Award).Grant Funding SourceFSHN
All‐trans retinoic acid up regulates matrix metalloproteinase‐9 activity by murine C57BL/6J myeloid dendritic cells
Authors: Lackey Denise Elizabeth , Hoag Kathleen Ann 
Published: June 2021

Myeloid dendritic cells (DC) are specialized cells for antigen presentation. Upon activation in peripheral tissues, DC migrate to lymph nodes to present antigen to and activate T cells. Matrix metalloproteinase (MMP)‐9 is a gelatinase essential for DC migration to sites of infection and inflammation as well as to lymph nodes. We have previously shown that all‐trans retinoic acid (atRA), a bioactive metabolite of vitamin A, is important for release of DC from the surface of the tissue culture dish in vitro and that it significantly augments MMP‐9 mRNA and protein production. In the current studies, we investigated the effects of atRA on MMP‐9 activity related to DC adhesion in vitro. Mouse bone marrow cells cultured under myeloid DC generating conditions in the presence of a retinoic acid receptor antagonist demonstrated decreased gelatinase activity compared to cells rescued with atRA treatment for the last 48 hours of the culture period. DC cultured in the presence of atRA and a specific MMP‐9 inhibitor showed significant increase in the adherent cell yield and percentage of total cells and DC that are adherent in a dose dependent manner compared to cultures treated with atRA only for the full culture period. These data suggest that atRA regulates DC adhesion in vitro through MMP‐9 activity.Grant Funding SourceDepartment of Food Science and Human Nutrition, Michigan State University
Effects of quercetin on skeletal muscle mitochondrial biogenesis and performance in untrained males
Authors: Williams Ashley Silberman , Nieman David C. , Jin Fuxia , Sobieraj James , Shanely Andrew , McAnulty Steve R. , Triplett N. Travis , Austin Melanie 
Published: June 2021

We determined the influence of 2‐weeks quercetin supplementation (1000 mg/day) compared to placebo on exercise performance and markers of skeletal muscle mitochondrial biogenesis in 26 untrained, physically inactive, young adult males. Utilizing a randomized, crossover design with a 2‐week washout period, subjects provided blood and muscle biopsy samples pre‐ and post‐supplementation periods, and were given 12‐minute time trials on 15% graded treadmills following 60‐min moderate exercise pre‐loads at 60% VO2max. Plasma quercetin levels rose significantly during the two‐week quercetin compared to placebo supplementation period. During the 12‐minute trial (15% treadmill grade, self‐selected speed), the net change in distance achieved was significantly greater with quercetin compared to placebo (29.5±11.5 vs. ‐11.9±16.0 m, respectively, P=0.038). Skeletal muscle mRNA expression tended to increase during supplementation with quercetin compared to placebo for SIRT‐1 (P‐value=0.152), PGC‐1α (P=0.192), cytochrome c oxidase (P=0.081), and citrate synthase (P=0.166). In summary, 1000 mg/d quercetin supplementation for 2 weeks by untrained males was associated with an improvement in 12‐minute treadmill time trial performance and 16% to 25% increases above placebo levels for mRNA expression for four genes related to mitochondrial biogenesis.Supported by a Grant from Quercegen Pharma
Examine the Over Time Shifts of Under‐ to Overnutrition Problems In India
Authors: Wang Youfa , Chen Hsin‐Jen , Shaikh Saijuddin , Mathur Prashant 
Published: June 2021

It is speculated obesity has increased in India in recent years thank to economic development and to follow trends observed in many other courtiers. Based on a systematic literature search on PubMed and other data sources, we examined the trends in overweight, obesity and undernutrition in recent decades in India. Most published studies were based on regional or local surveys in urban areas, while good representative data from the India National Family Health Surveys (NFHS, 1992‐93, 1998‐99, and 2005‐06) allowed for examining the shifts at national level. Overall, available data showed that in India, prevalence of overweight was low while that of undernutrition remained high, in children and adults. Overweight was more prevalent in female, urban, and high‐socioeconomic status (SES) groups. NFHS showed that overweight rates in women and preschool children did not increase much in the last decade: 10.6% and 1.6% in 1998‐99 to 12.6% and 1.5% in 2005‐06, respectively. As for underweight, NFHS 2005‐06 showed high prevalence among ever married women (about 35%) and preschool children (about 42%). Thus, India's nationwide overweight/obesity prevalence has been relatively stable in past decade, but in some urban‐ and high‐SES groups it has increased and reached a high level. Factors associated with undernutrition need closer examination; prevention of obesity should be targeted at the high‐risk groups simultaneously.This study is supported by Johns Hopkins University.
Anemia prevalence in Honduran children is significantly higher at increased altitudes
Authors: Kemmer Teresa Marie , Gidvani Vinod , Lougee Douglas , Coello Miguel , Amador Wilmer , Aviles Ricardo , Saenz Guillermo , Duron Carlos 
Published: June 2021

When determining anemia at altitudes >3,000 ft, hemoglobin (Hb) concentration values are adjusted. Objectives of this study were to determine 1) prevalence of anemia in children ages 6‐60 months living in rural Honduras and 2) if prevalence of anemia varies depending on altitude.Random sampling was used and data were collected at the household level in three health regions in Honduras. On‐the‐spot Hb levels were obtained and anemia was determined using age specific altitude adjusted Hb concentration values.Data were obtained from 1024 children (49.6% female). Mean age was 32.45 mo. Mean altitude was 4703 ft. Overall anemia prevalence was 31.1%. Anemia prevalence by region (mean altitude in ft) was Chinacla (4995), 26.9%; Santiago de Purlinga (4278), 28.3%; and Lepaterique (4909), 35.0%. In children living at >5,000 ft, 41.4% were anemic and 27.7% living at <5,000 ft were anemic (P=0.000). By using logistic regression and controlling for age, gender, and health region, anemia was associated with lower age (P=0.000), health region (P=0.02), and higher altitude (P=0.005).Anemia prevalence is high within the three mountainous health regions evaluated. Anemia prevalence is significantly higher in children living at altitudes > 5,000 ft. Funded by: US Air Force Southern Command, South Dakota State University, and the Center for Disaster and Humanitarian Assistance Medicine.
Augmentation of the Anticancer Effect of Proteasome Inhibitors by Butyrate in Human Colorectal Carcinoma
Authors: Abaza Mohamed Salah I. 
Published: June 2021

The ubiquitin‐proteasome pathway plays a critical role in the degradation of cellular proteins and cell cycle control. Dysregulating the degradation of such proteins should have profound effects on tumor growth and causes cells to undergo apoptosis. This study deals with the apoptotic effect of both proteasome inhibitors; MG115, MG132, proteasome inibitor‐1 (PSI‐1), proteasome inhibitor‐2 (PSI‐2) and epoxomicin; and sodium butyrate (NaB), their synergistic interaction and whether NaB , a natural product capable of inducing apoptosis in a number of tumor cells and exhibit a low degree of clinical toxicity, can enhance the anticancer effect of the proteasome inhibitors in colorectal cancer. The results showed that proteasome inhibitors and NaB inhibited the proliferation cancer cells in a dose and time dependent manner. The combinations of MG115, MG132, PSI‐1, PSI‐2 or epoxomicin and NaB produced prominent, additive and/or synergistic dose and time dependent growth inhibitory effects as well as a marked induction of apoptosis compared to single treatment with proteasome inhibitors or NaB. Cancer cells treated with NaB, proteasome inhibitors and their combinations were growth arrested at G1, G2‐M/S and G1 or S/G2‐M phases of cell cycle, respectively. p53, p21Waf1 , p27Kip1 and Bax were over‐expressed. Meanwhile, Bcl2 was down‐regulated after treatment with proteasome inhibitors and their combinations with NaB. Taken together, these results indicated a synergistic interaction between proteasome inhibitors and sodium butyrate that could represent a new tool in tumor therapy.This study was supported by Kuwait University, Research Grant No. SL04‐02
Dysregulation of MicroRNAs that Regulate DNMT3b Expression in Primary Breast Cancers
Authors: Sandhu Rupninder , Coleman William B 
Published: June 2021

A subset of breast cancer cell lines express a hypermethylation defect related to DNMT3b overexpression resulting from loss of expression of regulatory microRNAs (miRs). Most primary breast cancers overexpress DNMT3b compared to normal breast epithelia, and certain subsets of breast cancer (basal‐type) display gene expression signatures that reflect methylation‐dependent silencing of multiple genes, consistent with the expression of a hypermethylation defect in vivo. Several miRs have been implicated in the regulation of DNMT3b. We examined the expression of miRs‐29a, 29b, 29c, 148a, and 148b, in a group of 15 primary breast cancers (n=6 luminal A, n=2 luminal B, n=2 Her2+, n=5 basal) and two normal breast tissues. miR expression levels <50% of normal were found in 9/15 (60%) tumors for 29a/29c, 10/15 (67%) tumors for 29b, 12/15 (80%) tumors for 148a, and 8/15 (53%) for 148b. Further, 12/15 (80%) tumors lost expression =2 miRs, 9/15 (60%) lost =3 miRs, and 8/15 (53%) lost =4 miRs. The aggregate miR expression score did not differ for luminal A versus basal breast cancers, suggesting that loss of additional factors may govern the hypermethylation defect. These results suggest that loss of expression of miRs‐29a, 29b, 29c, 148a, and 148b occurs commonly among primary breast cancers, but may contribute to the expression of a hypermethylation defect in a subset of these neoplasms.Support: NIH CA 78343
Autocrine serotonin signaling mediates spontaneous canine myxomatous mitral valve disease
Authors: Disatian Sirilak , Orton Christopher 
Published: June 2021

Serotonin and serotonergic drugs are known to cause myxomatous‐like valvulopathy, but the role of serotonin in spontaneous myxomatous valve disease (MVD) is unknown. The study objective was to test the hypothesis that autocrine serotonin signaling mediates spontaneous MVD.METHODSNormal and myxomatous mitral valves from dogs were studied. Expression of serotonin 2B receptor (5HT2BR), tryptophan hydroxylase 1 (TPH1), serotonin transmembrane transporter (SERT), total and phosphorylated extracellular signaling‐regulated kinase (ERK)1/2 were studied by immunohistochemistry and immunoblot analysis.RESULTSBoth 5HT2BR and TPH1, the key serotonin synthetic enzyme, were increased in myxomatous valves; whereas SERT, a key protein in serotonin metabolism, was decreased in myxomatous valves. Phosphorylated, but not total, ERK1/2 was increased in myxomatous valves consistent with enhanced active serotonin signaling.CONCLUSIONExpression patterns for key serotonin signaling proteins suggest that autocrine serotonin signaling mediates spontaneous canine MVD. Research supported by the Heart to Heart foundation.
Skeletal muscle‐specific overexpression of insulin‐like growth factor I (IGF‐1) decreases oxidative stress and prevents angiotensin II‐induced skeletal muscle wasting: novel potential therapy to treat cachexia in congestive heart failure
Authors: Sukhanov Sergiy , Semprun‐Prieto Laura , Yoshida Tadashi , Vaughn Charlotte , Delafontaine Patrick 
Published: June 2021

Congestive heart failure is associated with elevated levels of angiotensin II (ANG) and skeletal muscle wasting (cachexia). We have shown that ANG induces cachexia and increases oxidative stress in FVB mice. Since we also found that IGF‐1 exerts anti‐oxidant effect in a murine model we hypothesized that IGF‐1 overexpression would decrease ANG‐induced cachexia and/or oxidative stress.Mice overexpressing IGF‐1 under control of the skeletal muscle‐specific type II myosin light chain promoter (MLC) and control FVB mice were infused with 1 ug/kg ANG or vehicle (SHM) for 7d. ANG decreased skeletal muscle weight in FVB (ANG/SHM, gastrocnemius: 99.8±3.6/122.3±4.2mg; tibialis anterior: 32.0±1.3/41.3±1.3mg; quadriceps:117.6±6.1/160.6±6.7mg), however no significant cachexia was found in ANG‐infused MLC. ANG induced leftward shift in myofibers number/size distribution and decreased cross‐sectional area (CSA) of type I and II myofibers in FVB (type I, 443±22/528±28 um2; type II, 620±40/835±44 um2) without effect on myofibers distribution and CSA in MLC (immunostaining with isoform‐specific a/b). ANG increased superoxides in FVB by 67±8% (p<0.05) but did not significantly change superoxides in MLC (assay with superoxide‐sensitive dye L‐012). ANG‐induced superoxides were suppressed by apocynin (a specific NADPH oxidase inhibitor) and also ANG increased NOX4 (a NADPH oxidase subunit) expression (RT‐PCR) in both mouse models, however NOX4 upregulation was greater in FVB compared to MLC (3.6‐ vs. 2.1‐fold increase). Thus, IGF‐1 overexpression suppresses oxidative stress and efficiently blocks skeletal muscle wasting, possibly via inhibition of NADPH oxidase‐mediated superoxide formation.
PI3K‐R1 expression in hepatic tissue of horses with laminitis
Authors: Carlisle Katherine , McGeachy Matthew , Garza Frank , Stokes Ashley Michelle 
Published: June 2021

Phosphatidylinositol‐3‐Kinase (PI3K) is an inhibitor of pro‐inflammatory processes regulated by two converging pathways. It is a cytoplasmic component of the Toll‐Like Receptor Signaling Pathway and is also affected by insulin receptor activation. The objective was to examine gene expression of the regulatory subunit p85 (R1) of PI3K in equine liver samples from normal (n=13), naturally acquired laminitis (n=11), experimentally induced laminitis (n=7), and metabolic disorder (n=3) cases.Total cellular RNA was extracted, analyzed by agarose gel electrophoresis, quantified by spectrophotometry, reverse transcribed to cDNA, and quantified by TaqMan RT‐PCR.The most significant finding of this study was a difference between PI3K expression and laminitis activity (p=0.0441). Horses with active cases of laminitis, Obel grade ¡Ý 1, demonstrated significantly less expression of PI3K than horses with inactive cases (fold decrease=10.26). We also found a marked increase of PI3K in horses with metabolic disorders compared to those with laminitis (fold increase=14.949).Our study suggests a relationship may exist between PI3K down‐regulation and the pathogenesis of laminitis. Therefore, PI3K‐R1 deserves further investigation as an inflammatory mediator that can be targeted in prevention and treatment of laminitis.Funding provided by the LSU Equine Health Studies Program.
sEH‐deficiency attenuates neointima formation in the femoral artery cuff model of hyperlipidemic mice
Authors: Revermann Marc , Schloss Manuel , Barbosa‐Sicard Eduardo , Fleming Ingrid , Morriseau Christophe , Hammock Bruce , Brandes Ralf Peter 
Published: June 2021

Epoxyeicosatrienoic acids (EETs) have anti‐inflammatory effects and promote normal endothelial function. The soluble epoxide hydrolase (sEH) metabolizes EETs to their less active diols. We hypothesized that knockdown and inhibition of sEH prevents neointima formation in hyperlipidemic ApoE‐/‐ mice induced by the femoral artery cuff model. Inhibition of sEH by 12‐(3‐adamantan‐1‐yl‐ureido) dodecanoic acid (AUDA) or knockout of the enzyme significantly increased the plasma EET concentration. sEH activity was detectable in femoral arteries. sEH‐knockout and inhibition results in a significant reduction of neointima formation (50±6,3% and 42±4,7% reduction in intima/media‐ratio, p<0.05). The proinflammatory gene expression at the site of cuff placement was significantly reduced in sEH‐/‐‐mice. Moreover, an in vivo‐BrdU‐assay revealed significantly attenuated SMC‐proliferation in sEH‐/‐. Accordingly, SMC‐migration activity in cultured cells was attenuated by EETs and this effect was abolished by protein kinase A inhibition. These observations suggest that inhibition of sEH prevents vascular remodelling.German Research Foundation & Goethe‐University
NADPH oxidase is critically involved in CCL2‐induced endothelial cell activation
Authors: Zhang Wenbo , Rojas Modesto A. , Wiseman Dean A. , Behzadian M.A. , Bartoli Manuela , Black Stephen M. , Caldwell Robert W. , Caldwell Ruth B. 
Published: June 2021

CCL2 plays an important role in vascular diseases via recruitment of leukocytes and by altering integrity of the vascular wall. Molecular mechanisms of direct CCL2‐induced activation of vascular endothelial cells (ECs) are largely unknown. Here we assessed the hypothesis that NADPH oxidase is critically involved in regulating EC responses to CCL2. Studies using EPR spin trap CMH and DCF imaging showed that CCL2 induces a significant and time‐dependent increase in the reactive oxygen species (ROS) which was blocked by pretreating ECs with NADPH oxidase inhibitors or anti‐oxidants. Measurement of directed EC migration showed that CCL2 induced a dose‐dependent increase in EC migration. The increase in migration was blocked by inhibiting NADPH oxidase activity. Immunoblot analysis revealed that CCL2 rapidly activates Akt, ERK, and p38 MAPK. Pretreatment of ECs with NADPH oxidase inhibitors, antioxidants, or the superoxide scavenger, significantly attenuated CCL2‐induced activation of Akt, but did not alter the activation of ERK or p38 MAPK. Inhibiting activity of mitochondrial complex II did not prevent the CCL2‐induced Akt activation. These studies indicate that CCL2‐mediated activation of ECs and induction of EC migration are mediated by NADPH oxidase‐derived ROS and that the process involves the redox dependent activation of Akt.Supported by EY04618, EY11766, and VA (R.B.C.); HL70215 (R.W.C); AHA (W. Z.)
In vitro system for studying blood, perfluorocarbons (PFC) and Sickle Cell Anemia
Authors: Narayanan Srinivasan Vasudevan , Berger Brian , Torres Filho Ivo 
Published: June 2021

PFCs are inert compounds that dissolve more oxygen (O2) than plasma. A mixture of PFC and sickle cell blood could potentially hold and deliver more O2 to tissues, compensating for sickle cell red blood cell's (RBC) decreased affinity for O2. A system was developed for in vitro studies using blood mixed with PFC. The system (priming volume: 10 ml) includes a computer‐controlled pump, gas mixer, oxygenator, deoxygenator and interconnected tubing that allowed the flowing blood to be exposed to various O2 and CO2 tensions, yielding controlled levels of hemoglobin O2 saturation (SO2) and O2 partial pressures (PO2). SO2 and PO2 were measured using a blood gas analyzer and a CO‐oximeter. With the addition of 5, 10, and 20% of PFC by volume of blood, the total O2 content, O2 delivery and consumption increased linearly with the PFC concentration. The data suggest increased O2 transport by the PFC. The SO2 of blood mixed with PFC did not differ significantly from baseline. Changes in blood cell morphology can also be evaluated at each oxygenation level and PFC concentration using video‐microscopy. The percentage of RBC that sickle at a given PO2 with and without PFC will be determined. The system allows several variables to be studied using blood sampled from animals and patients.Support: Virginia Commonwealth University.