bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between sequence conservation and structural thermodynamics of microRNA precursors from human, mouse, and chicken genomes
Authors: Ni Ming , Shu Wenjie , Bo Xiaochen , Wang Shengqi , Li Songgang 
Published: October 2010

AbstractBackgroundPrevious studies have shown that microRNA precursors (pre-miRNAs) have considerably more stable secondary structures than other native RNAs (tRNA, rRNA, and mRNA) and artificial RNA sequences. However, pre-miRNAs with ultra stable secondary structures have not been investigated. It is not known if there is a tendency in pre-miRNA sequences towards or against ultra stable structures? Furthermore, the relationship between the structural thermodynamic stability of pre-miRNA and their evolution remains unclear.ResultsWe investigated the correlation between pre-miRNA sequence conservation and structural stability as measured by adjusted minimum folding free energies in pre-miRNAs isolated from human, mouse, and chicken. The analysis revealed that conserved and non-conserved pre-miRNA sequences had structures with similar average stabilities. However, the relatively ultra stable and unstable pre-miRNAs were more likely to be non-conserved than pre-miRNAs with moderate stability. Non-conserved pre-miRNAs had more G+C than A+U nucleotides, while conserved pre-miRNAs contained more A+U nucleotides. Notably, the U content of conserved pre-miRNAs was especially higher than that of non-conserved pre-miRNAs. Further investigations showed that conserved and non-conserved pre-miRNAs exhibited different structural element features, even though they had comparable levels of stability.ConclusionsWe proposed that there is a correlation between structural thermodynamic stability and sequence conservation for pre-miRNAs from human, mouse, and chicken genomes. Our analyses suggested that pre-miRNAs with relatively ultra stable or unstable structures were less favoured by natural selection than those with moderately stable structures. Comparison of nucleotide compositions between non-conserved and conserved pre-miRNAs indicated the importance of U nucleotides in the pre-miRNA evolutionary process. Several characteristic structural elements were also detected in conserved pre-miRNAs.
Polyploid genome of Camelina sativarevealed by isolation of fatty acid synthesis genes
Authors: Hutcheon Carolyn , Ditt Renata F , Beilstein Mark , Comai Luca , Schroeder Jesara , Goldstein Elianna , Shewmaker Christine K , Nguyen Thu , De Rocher Jay , Kiser Jack 
Published: October 2010

Abstract

Background

Camelina sativa, an oilseed crop in the Brassicaceae family, has inspired renewed interest due to its potential for biofuels applications. Little is understood of the nature of the C. sativa genome, however. A study was undertaken to characterize two genes in the fatty acid biosynthesis pathway, fatty acid desaturase (FAD) 2 and fatty acid elongase (FAE) 1, which revealed unexpected complexity in the C. sativa genome.

Results
In C. sativa, Southern analysis indicates the presence of three copies of both FAD2 and FAE1 as well as LFY, a known single copy gene in other species. All three copies of both CsFAD2 and CsFAE1 are expressed in developing seeds, and sequence alignments show that previously described conserved sites are present, suggesting that all three copies of both genes could be functional. The regions downstream of CsFAD2 and upstream of CsFAE1 demonstrate co-linearity with the Arabidopsis genome. In addition, three expressed haplotypes were observed for six predicted single-copy genes in 454 sequencing analysis and results from flow cytometry indicate that the DNA content of C. sativa is approximately three-fold that of diploid Camelina relatives. Phylogenetic analyses further support a history of duplication and indicate that C. sativa and C. microcarpa might share a parental genome.

Conclusions
There is compelling evidence for triplication of the C. sativa genome, including a larger chromosome number and three-fold larger measured genome size than other Camelina relatives, three isolated copies of FAD2, FAE1, and the KCS17-FAE1 intergenic region, and three expressed haplotypes observed for six predicted single-copy genes. Based on these results, we propose that C. sativa be considered an allohexaploid. The characterization of fatty acid synthesis pathway genes will allow for the future manipulation of oil composition of this emerging biofuel crop; however, targeted manipulations of oil composition and general development of C. sativa should consider and, when possible take advantage of, the implications of polyploidy.
Association of methylenetetrahydrofolate reductase C677T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations
Authors: Zhang Lin , Yin Rui-Xing , Liu Wan-Ying , Miao Lin , Wu Dong-Feng , Aung Lynn Htet Htet , Hu Xi-Jiang , Cao Xiao-Li , Wu Jin-Zhen , Pan Shang-Ling 
Published: October 2010

Abstract

Background
The association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and serum lipid profiles is still controversial in diverse ethnics. Bai Ku Yao is an isolated subgroup of the Yao minority in China. The aim of the present study was to eveluate the association of MTHFR C677T polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

Methods
A total of 780 subjects of Bai Ku Yao and 686 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the MTHFR C677T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.

Results
The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.05-0.001). The frequency of C and T alleles was 77.4% and 22.6% in Bai Ku Yao, and 60.9% and 39.1% in Han (P < 0.001); respectively. The frequency of CC, CT and TT genotypes was 58.7%, 37.3% and 4.0% in Bai Ku Yao, and 32.6%, 56.4% and 11.0% in Han (P < 0.001); respectively. The levels of TC and LDL-C in both ethnic groups were significant differences among the three genotypes (P < 0.05-0.01). The T allele carriers had higher serum TC and LDL-C levels than the T allele noncarriers. The levels of ApoB in Han were significant differences among the three genotypes (P < 0.05). The T allele carriers had higher serum ApoB levels as compared with the T allele noncarriers. The levels of TC, TG and LDL-C in Bai Ku Yao were correlated with genotypes (P < 0.05-0.001), whereas the levels of LDL-C in Han were associated with genotypes (P < 0.001). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, cigarette smoking, and blood pressure in the both ethnic groups.

Conclusions
The differences in serum TC, TG, LDL-C and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of the MTHFR C677T or different MTHFR gene-enviromental interactions.
Spatiotemporal expression of the serine protease inhibitor, SERPINE2, in the mouse placenta and uterus during the estrous cycle, pregnancy, and lactation
Authors: Chern Schu-Rern , Li Sheng-Hsiang , Lu Chung-Hao , Chen Edmund I Tsuen 
Published: October 2010

Abstract

Background
SERPINE2, also known as glia-derived nexin or protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent serpins that modulates the activity of the plasminogen activator (PA) and was implicated in tissue remodeling. In this study, we investigated the expression patterns of SERPINE2 in the mouse placenta and uterus during the estrous cycle, pregnancy, and lactation.

Methods
SERPINE2 was purified from mouse seminal vesicle secretion using liquid chromatography (LC) and identified by LC/tandem mass spectrometry. The antiserum against the SERPINE2 protein was raised in rabbits. To reveal the uterine and placental expression of SERPINE2, tissues at various stages were collected for real-time PCR quantification, Western blotting, and immunohistochemical staining.

Results
Serpine2 mRNA was the major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation, although Serpine1 mRNA had higher expression levels than Serpine2 mRNA in the placenta. Plat seemed to be the major PA in the mouse uterus and placenta. Antiserum against the SERPINE2 protein specifically recognized two forms of SERPINE2 and an extra 75-kDa protein, which was probably a complex of SERPINE2 with a certain protease, from among thousands of protein components in the tissue extract as demonstrated by Western blotting. In the uterus, SERPINE2 was primarily localized in luminal and glandular epithelial cells but it also was detected in circular and longitudinal smooth muscle cells during the estrous cycle and lactation. It was prominently expressed in decidual stroma cells, the metrial gland, and endometrial epithelium of the pregnant uterus. In the placenta, SERPINE2 was expressed in trophoblasts of the labyrinth and spongiotrophoblasts. However, its expression was remarkably reduced in giant cells which existed in the giant cell-decidual junction zone. In contrast, prominent expression of SERPINE2 seemed to be detected on clusters of glycogen cells near the junction zone. In addition, yolk sac membranes also showed high expression of SERPINE2.

Conclusions
These findings indicate that SERPINE2 is a major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation. It may participate in the PA-modulated tissue remodeling process in the mouse placenta and uterus.
Fcγ receptors are required for NF-κB signaling, microglial activation and dopaminergic neurodegeneration in an AAV-synuclein mouse model of Parkinson's disease
Authors: Cao Shuwen , Theodore Shaji , Standaert David G 
Published: October 2010

AbstractOverexpression of alpha-synuclein (α-SYN), a protein which plays an important role in the pathogenesis of Parkinson's disease (PD), triggers microglial activation and adaptive immune responses, and leads to neurodegeneration of dopaminergic (DA) neurons. We hypothesized a link between the humoral adaptive immune response and microglial activation in α-SYN induced neurodegeneration. To test this hypothesis, we employed adeno-associated virus serotype 2 (AAV2) to selectively over-express human α-SYN in the substantia nigra (SN) of wild-type mice and FcγR-/- mice, which lack high-affinity receptors for IgG. We found that in wild-type mice, α-SYN induced the expression of NF-κB p65 and pro-inflammatory molecules. In FcγR-/- mice, NF-κB activation was blocked and pro-inflammatory signaling was reduced. Microglial activation was examined using immunohistochemistry for gp91PHOX. At four weeks, microglia were strongly activated in wild-type mice, while microglial activation was attenuated in FcγR-/- mice. Dopaminergic neurodegeneration was examined using immunohistochemistry for tyrosine hydroxylase (TH) and unbiased stereology. α-SYN overexpression led to the appearance of dysmorphic neurites, and a loss of DA neurons in the SN in wild-type animals, while FcγR-/- mice did not exhibit neuritic change and were protected from α-SYN-induced neurodegeneration 24 weeks after injection. Our results suggest that the humoral adaptive immune response triggered by excess α-SYN plays a causative role in microglial activation through IgG-FcγR interaction. This involves NF-κB signaling, and leads to DA neurodegeneration. Therefore, blocking either FcγR signaling or specific intracellular signal transduction events downstream of FcγR-IgG interaction, such as NF-κB activation, may be viable therapeutic strategies in PD.
Increased Aripiprazole Concentrations in an HIV-Positive Male Concurrently Taking Duloxetine, Darunavir, and Ritonavir
Authors: Aung Gregory L , O'Brien John G , Tien Pamela G , Kawamoto Laura S 
Published: October 2010

Objective: To report a case of increased aripiprazole concentrations during coadministration with darunavir, ritonavir, and duloxetine. Case Summary: A 43-year-old HIV-positive Hispanic man received darunavir/ritonavir-based antiretroviral therapy (ART) in addition to aripiprazole and duloxetine for depression and anxiety. A month after the aripiprazole dosage was increased to 50 mg dailry, the patient developed confusion and loss of coordination. Weeks later, he presented to the emergency department with fever, cough, headache, neck stiffness, back pain, and blurred vision and was admitted for possible meningitis. Because symptoms improved with pain control and intravenous fluids during hospitalization, he was discharged within a couple days after admission. One month later he was readmitted for worsening symptoms, and the resulting diagnostic workup showed unremarkable findings except for lymphadenopathy (LAD). This finding was attributed to discontinuing ARTs after his first admission, He was discharged on aripiprazole 50 mg daily, darunavir 800 mg daily, ritonavir 100 mg daily, and duloxetine 60 mg daily. A random steady-state concentration of aripiprazole was 1100 ng/mL (therapeutic concentration 100-200 ng/mL) obtained 49 days after discharge. Discussion: The Horn Drug Interaction Probability Scale demonstrated a possible relationship between the increased aripiprazole concentration and coadministration of darunavir/ritonavir and duloxetine, which inhibit CYP3A4 and 2D6. Potential confounders to the increased concentration include duloxeline inhibition of CYP2D6 polymorphism, possible 2D6 polymorphism, and exceeding aripiprazole's maximum dose. The initial presentation of confusion and loss of coordination may have been early signs of aripiprazole toxicity, which relapsed as shown by his symptoms prior to admission. Conclusions: The interaction between aripiprazole and darunavir, ritonavir, and duloxetine may be significant. Clinicians should be cognizant of increased risk of aripiprazole toxicity in HIV-positive patients concurrently taking ritonavir-boosted ART and other cytochrome P450 inhibitors like duloxetine. Dose adjustments or monitoring parameters should be an area of research and discussion.
Assessing the Effect of the Surviving Sepsis Campaign Treatment Guidelines on Clinical Outcomes in a Community Hospital
Authors: Patel Gita Wasan , Roderman Nicki , Gehring Hollie , Saad John , Bartek William 
Published: October 2010

Background: Bundles yield a reduction in mortality in patients with sepsis, but the majority of the data is from large academic centers. The ability of a community hospital to implement a sepsis bundle successfully, however, has not been investigated. Objective: To examine the effect of a collaborative 2-part sepsis bundle on clinical outcomes and mortality at a community hospital. Methods: The study included all patients with severe sepsis/septic shock over the age of 18 years admitted to the intensive care unit (ICU) from 2006 to 2007 who were not treated with a bundle (n = 53) and those who were treated with a bundle (n = 59). Data collected included demographics; initiation of vasopressors; days on vasopressors; blood glucose; use of drotrecogin alfa (activated), steroids, and ventilator; ICU/hospital lengths of stay; ventilator days; time to culture; time to first dose of antibiotics; time to transfer from emergency department to ICU; fluid resuscitation in the first 24 hours; percentage of patients started on dialysis; and mortality. Results: Demographics; blood glucose; use of drolrecogin alfa (activated), steroids and ventilator; ICU/hospital lengths of stay; and ventilator days were statistically similar between groups. Median time to cultures, first dose of antibiotics, and transfer to ICU were all reduced with the bundle. Percentage of non-bundle patients on vasopressors was 87% versus 66.7% of bundle patients (p = 0.011) and number of median days on vasopressors was reduced. Fewer bundle patients were initiated on dialysis (0%) versus non-bundle patients (14.8%) (p = 0.02). Median fluid administered in the first 24 hours was 2200 mL (10-13,996 mL) for non-bundle patients and 7143 mL (1000-19,104 mL) for bundle patients (p < 0.001). Mortality was 61.1% in the non-bundle group versus 20% with the bundle (p < 0.001). Conclusions: Implementation of a 2-part sepsis bundle based on the Surviving Sepsis Campaign Guidelines can yield a positive impact on clinical outcome and mortality in a nonacademic, community hospital setting.
Spironolactone Management of Resistant Hypertension
Authors: Marrs Joel C 
Published: October 2010

Objective:To review the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone in the treatment of resistant hypertension.Data Sources:A literature search was conducted using MEDLINE (1966-July 2010), International Pharmaceutical Abstracts (1970-July 2010), and Cochrane database (2009) for the key words spironolactone or resistant hypertension. References cited in the articles were reviewed for additional information.Study Selection and Data Extraction:English-language literature reporting pharmacology data from animal studies and clinical trials evaluating the pharmacology, pharmacokinetics, pharmacodynamics, efficacy data, and adverse effects of spironolactone were included.Data Synthesis:Spironolactone is a potassium-sparing diuretic with anti-aldosterone effects that are beneficial in the management of hypertension. Spironolactone has shown improvement in 5 prospective studies and 1 retrospective study evaluating its blood pressuring–lowering abilities in patients with resistant hypertension. Specifically, the average blood pressure lowering noted in these trials with the addition of spironolactone in patients with resistant hypertension was 22/10 mm Hg. Trials evaluating spironolactone's role in resistant hypertension treatment have identified hyperkalemia, gynecomastia, and renal insufficiency as the major adverse effects that warrant monitoring.Conclusions:Spironolactone is an appropriate antihypertensive medication to add to treatment of patients with resistant hypertension (≥3 antihypertensive medications at optimal doses) not at their blood pressure goal. In patients considered to have resistant hypertension, secondary causes should be ruled out.
Incidence of Cleft Lip and Palate in Uganda
Authors: Dreise Marieke , Galiwango George , Hodges Andrew 
Published: October 2010

Objective The purpose of the study was to estimate the need for resources for cleft repairs in Uganda by determining the overall incidence of -facial clefts and the ratio of isolated cleft lip to isolated cleft palate to cleft lip and palate. Design A 1-year prospective study was implemented in seven hospitals and health centers with maternity units in and around Kampala. All live babies were examined for cleft lip and/or palate at birth. The birth of a baby with a cleft was communicated to the research coordinator by maternity staff, and the babies were assessed within 24 hours of delivery. Maternity data (live births) for each center were collected monthly to determine the denominator. Results Over the course of 1 year (February 1, 2008 to January 31, 2009), 26,186 babies were delivered. Nineteen babies had a cleft lip and/or palate, giving an incidence of 0.73 in 1000; 12 of the 19 babies (63.2%) had a cleft lip and palate, six (31.2%) had an isolated cleft lip, and only one (5.3%) had an isolated cleft palate. The ratio of boys to girls was 1.1:1. Conclusions The incidence of clefts in this study was 0.73 in 1000. With an estimated 1100 babies born with a cleft per year, this would result in the need for 1800 cleft repairs for babies in Uganda (695 babies needing two repairs each). These data will be helpful to advocate for and plan the necessary resources to effectively treat this condition.
Cyclic GMP Kinase I Modulates Glucagon Release From Pancreatic α-Cells
Authors: Leiss Veronika , Friebe Andreas , Welling Andrea , Hofmann Franz , Lukowski Robert 
Published: October 2010

OBJECTIVEThe physiologic significance of the nitric oxide (NO)/cGMP signaling pathway in islets is unclear. We hypothesized that cGMP-dependent protein kinase type I (cGKI) is directly involved in the secretion of islet hormones and glucose homeostasis.RESEARCH DESIGN AND METHODSGene-targeted mice that lack cGKI in islets (conventional cGKI mutants and cGKIα and Iβ rescue mice [α/βRM] that express cGKI only in smooth muscle) were studied in comparison to control (CTR) mice. cGKI expression was mapped in the endocrine pancreas by Western blot, immuno-histochemistry, and islet-specific recombination analysis. Insulin, glucagon secretion, and cytosolic Ca2+ ([Ca2+]i) were assayed by radioimmunoassay and FURA-2 measurements, respectively. Serum levels of islet hormones were analyzed at fasting and upon glucose challenge (2 g/kg) in vivo.RESULTSImmunohistochemistry showed that cGKI is present in α- but not in β-cells in islets of Langerhans. Mice that lack α-cell cGKI had significantly elevated fasting glucose and glucagon levels, whereas serum insulin levels were unchanged. High glucose concentrations strongly suppressed the glucagon release in CTR mice, but had only a moderate effect on islets that lacked cGKI. 8-Br-cGMP reduced stimulated [Ca2+]i levels and glucagon release rates of CTR islets at 0.5 mmol/l glucose, but was without effect on [Ca2+]i or hormone release in cGKI-deficient islets.CONCLUSIONSWe propose that cGKI modulates glucagon release by suppression of [Ca2+]i in α-cells.
Comparison of Diabetes Control Among Haitians, African Americans, and Non-Hispanic Whites in an Urban Safety-Net Hospital
Authors: Vimalananda Varsha G. , Rosenzweig James L. , Cabral Howard J. , David Michele M. , Lasser Karen E. 
Published: October 2010

OBJECTIVE
To compare diabetes care and outcomes among Haitians, African Americans, and non-Hispanic whites.

RESEARCH DESIGN AND METHODS
We analyzed data from 715 Haitian, 1,472 African American, and 466 non-Hispanic white adults with diabetes using χ2 testing and multiple logistic regression.

RESULTS
Haitians had a higher mean A1C than African Americans (8.2 ± 1.9 vs. 7.7 ± 2.0%) and non-Hispanic whites (7.5 ± 1.7%) (both P &lt; 0.0001). There was no difference in completion of process measures. Haitians were more likely than non-Hispanic whites to have elevated LDL cholesterol or blood pressure. Macrovascular complications were fewer among Haitians than African Americans (adjusted odds ratio 0.35 [95% CI 0.23–0.55]), as were microvascular complications (0.56 [0.41–0.76]). Haitians also had fewer macrovascular (0.32 [0.20–0.50]) and microvascular (0.55 [0.39–0.79]) complications than non-Hispanic whites.

CONCLUSIONS
Haitians have worse glycemic control than African Americans or non-Hispanic whites. Future research and interventions to improve diabetes care should target Haitians as a distinct racial/ethnic group.