bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth inhibition of an Araucaria angustifolia (Coniferopsida) fungal seed pathogen, Neofusicoccum parvum, by soil streptomycetes
Authors: Dalmas Fernando Rostirolla , Astarita Leandro , DeFilippis Luigi , Magel Elisabeth , Fiedler Hans-Peter , Bauer Robert , Hampp Rüdiger 
Published: July 2013

Abstract

Background
Araucariaceae are important forest trees of the southern hemisphere. Life expectancy of their seedlings can largely be reduced by fungal infections. In this study we have isolated and characterized such a fungus and investigated the potential of Streptomyces Actinobacteria from the respective rhizosphere to act as antagonists.

Results
The pathogenic fungus from Araucaria angustifolia seeds was identified by morphological markers (pore-associated Woronin-bodies) as belonging to the Pezizomycotina. Molecular data identified the fungus as Neofusicoccum parvum (Botryosphaeriaceae). Co-cultures on agar of this fungus with certain streptomycete isolates from the rhizosphere, and from the surface of Araucaria roots significantly reduced the growth of the fungus. HPLC analysis of the agar yielded streptomycete-specific exudate compounds which were partly identified. There were differences in compounds between single (bacteria, fungus) and dual cultures (bacteria + fungus).

Conclusion
Streptomycetes from the rhizosphere of Araucariaceae produce exudates which can suppress the development of pathogenic fungi in their seeds.
Fast selection of maribavir resistant cytomegalovirus in a bone marrow transplant recipient
Authors: Schubert Axel , Ehlert Karoline , Schuler-Luettmann Susanne , Gentner Eva , Mertens Thomas , Michel Detlef 
Published: July 2013

Abstract

Background
Human cytomegalovirus infections are still significant causes of morbidity and mortality in transplant recipients. The use of antiviral agents is limited by toxicity and evolving resistance in immunocompromised patients with ongoing viral replication during therapy. Here, we present the first documented case of genotypic resistance against maribavir in a bone marrow transplant (BMT) recipient.

Case presentation
The female 13-year-old patient was suffering from a refractory cytopenia. Ganciclovir, foscarnet, cidofovir, leflunomide and maribavir, an inhibitor of the cytomegalovirus UL97 protein, were administered to treat a therapy-resistant cytomegalovirus infection. Viral mutations conferring resistance against nucleotide and pyrophosphate analogs as well as maribavir (MBV) have evolved sequentially. Particularly, impressive was the fast emergence of multiple mutations T409M, H411Y and H411N conferring maribavir resistance after less than 6 weeks.

Conclusion
We describe the fast emergence of cytomegalovirus variants with different maribavir resistance associated mutations in a bone marrow transplant recipient treated with MBV 400 mg p.o. twice per day. The results suggest that a high virus load permitted a selection of several but distinct therapy-resistant HCMV mutants. Since a phase II study with MBV is intended for the treatment of resistant or refractory HCMV infections in transplant recipients this has to be kept in mind in patients with high viral loads during therapy (NCT01611974).
Mitochondrial DNA variant m.15218A > G in Finnish epilepsy patients who have maternal relatives with epilepsy, sensorineural hearing impairment or diabetes mellitus
Authors: Soini Heidi K , Moilanen Jukka S , Vilmi-Kerälä Tiina , Finnilä Saara , Majamaa Kari 
Published: July 2013

Abstract

Background
Mitochondrial diseases caused by mutations in mitochondrial DNA (mtDNA) affect tissues with high energy demand. Epilepsy is one of the manifestations of mitochondrial dysfunction when the brain is affected. We have studied here 79 Finnish patients with epilepsy and who have maternal first- or second-degree relatives with epilepsy, sensorineural hearing impairment or diabetes mellitus.

Methods
The entire mtDNA was studied by using conformation sensitive gel electrophoresis and PCR fragments that differed in mobility were directly sequenced.

Results
We found a common nonsynonymous variant m.15218A > G (p.T158A, MTCYB) that occurs in haplogroup U5a1 to be more frequent in patients with epilepsy. The m.15218A > G variant was present in five patients with epilepsy and in four out of 403 population controls (p = 0.0077). This variant was present in two branches in the phylogenetic network constructed on the basis of mtDNA variation among the patients. Three algorithms predicted that m.15218A > G is damaging in effect.

Conclusions
We suggest that the m.15218A > G variant is mildly deleterious and that mtDNA involvement should be considered in patients with epilepsy and who have a maternal history of epilepsy, sensorineural hearing impairment or diabetes mellitus.
Simvastatin decreases the level of heparin-binding protein in patients with acute lung injury
Authors: McAuley Daniel F , O’Kane Cecilia M , Craig Thelma R , Shyamsundar Murali , Herwald Heiko , Dib Karim 
Published: July 2013

Abstract

Background
Heparin-binding protein is released by neutrophils during inflammation and disrupts the integrity of the alveolar and capillary endothelial barrier implicated in the development of acute lung injury and systemic organ failure. We sought to investigate whether oral administration of simvastatin to patients with acute lung injury reduces plasma heparin-binding protein levels and improves intensive care unit outcome.

Methods
Blood samples were collected from patients with acute lung injury with 48 h of onset of acute lung injury (day 0), day 3, and day 7. Patients were given placebo or 80 mg simvastatin for up to 14 days. Plasma heparin-binding protein levels from patients with acute lung injury and healthy volunteers were measured by ELISA.

Results
Levels of plasma heparin-binding protein were significantly higher in patients with acute lung injury than healthy volunteers on day 0 (p = 0.011). Simvastatin 80 mg administered enterally for 14 days reduced plasma level of heparin-binding protein in patients. Reduced heparin-binding protein was associated with improved intensive care unit survival.

Conclusions
A reduction in heparin-binding protein with simvastatin is a potential mechanism by which the statin may modify outcome from acute lung injury.

Trial registration
Current controlled trials: ISRCTN70127774
Antileptospiral activity of xanthones from Garcinia mangostanaand synergy of gamma-mangostin with penicillin G
Authors: Seesom Weeranuch , Jaratrungtawee Amornmart , Suksamrarn Sunit , Mekseepralard Chantana , Ratananukul Piniti , Sukhumsirichart Wasana 
Published: July 2013

Abstract

Background
Leptospirosis, one of the most widespread zoonotic infectious diseases worldwide, is caused by spirochetes bacteria of the genus Leptospira. The present study examined inhibitory activity of purified xanthones and crude extracts from Garcinia mangostana against both non-pathogenic and pathogenic leptospira. Synergy between γ-mangostin and penicillin G against leptospires was also determined.

Methods
Minimal inhibitory concentrations (MIC) of crude extracts and purified xanthones from G. mangostana and penicillin G for a non-pathogenic (L. biflexa serovar Patoc) and pathogenic (L. interrogans serovar Bataviae, Autumnalis, Javanica and Saigon) leptospires were determined by using broth microdilution method and alamar blue. The synergy was evaluated by calculating the fractional inhibitory concentration (FIC) index.

Results
The results of broth microdilution test demonstrated that the crude extract and purified xanthones from mangosteen possessed antileptospiral activities. The crude extracts were active against all five serovars of test leptospira with MICs ranging from 200 to ≥ 800 μg/ml. Among the crude extracts and purified xanthones, garcinone C was the most active compound against both of pathogenic (MIC =100 μg/ml) and non-pathogenic leptospira (MIC = 200 μg/ml). However, these MIC values were higher than those of traditional antibiotics. Combinations of γ-mangostin with penicillin G generated synergistic effect against L. interrogans serovars Bataviae, Autumnalis and Javanica (FIC = 0.52, 0.50, and 0.04, respectively) and no interaction against L. biflexa serovar Patoc (FIC =0.75). However, antagonistic activity (FIC = 4.03) was observed in L. interrogans serovar Saigon.

Conclusions
Crude extracts and purified xanthones from fruit pericarp of G. mangostana with significant antibacterial activity may be used to control leptospirosis. The combination of xanthone with antibiotic enhances the antileptospiral efficacy.
Association of tumor necrosis factor-alpha promoter variants with risk of HPV-associated oral squamous cell carcinoma
Authors: Jin Lei , Sturgis Erich M , Zhang Yang , Huang Zhigang , Song Xicheng , Li Chao , Wei Qingyi , Li Guojun 
Published: July 2013

AbstractBackgroundTumor necrosis factor alpha (TNF-α) plays an important role in inflammation, immunity, and defense against infection and clearance of human papillomavirus (HPV). Thus, genetic variants may modulate individual susceptibility to HPV-associated oral squamous cell carcinoma (OSCC).MethodsIn this study we genotyped four common single nucleotide polymorphisms (SNPs) in theTNF-αpromoter [ −308G > A(rs1800629), -857C > T (rs1799724), -863C > A (rs1800630), and -1031T > C (rs1799964)] and determined HPV16 serology in 325 OSCC cases and 335 matched controls and tumor HPV status in 176 squamous cell carcinomas of the oropharynx (SCCOP) patients. Univariate and multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).ResultsWe found that HPV16 seropositivity alone was associated with an increased risk of OSCC (OR, 3.1; 95% CI, 2.1–4.6), and such risk of HPV16-associated OSCC was modified by each SNP. Patients with both HPV16 seropositivity and variant genotypes for each SNP had the highest risk when using patients with HPV16 seronegativity and a wild-type genotype as a comparison group. Moreover, similar results were observed for the combined risk genotypes of four variants and all such significant associations were more pronounced in several subgroups, particularly in SCCOP patients and never smokers. Notably, the combined risk genotypes of four variants were also significantly associated with tumor HPV-positive SCCOP.ConclusionTaken together, these results suggest thatTNF-αSNPs may individually or, more likely, jointly affect individual susceptibility to HPV16-associated OSCC, particularly SCCOP and never smokers. Validation of our findings is warranted.
Investigation of bulk hybrid heterojunction solar cells based on Cu(In,Ga)Se2 nanocrystals
Authors: Yen Yu-Ting , Lin Yi-Kai , Chang Shu-Hao , Hong Hwen-Fen , Tuan Hsing-Yu , Chueh Yu-Lun 
Published: July 2013

Abstract
This work presents the systematic studies of bulk hybrid heterojunction solar cells based on Cu(In, Ga)Se2 (CIGS) nanocrystals (NCs) embedded in poly(3-hexylthiophene) matrix. The CIGS NCs of approximately 17 nm in diameter were homogeneously blended with P3HT layer to form an active layer of a photovoltaic device. The blend ratios of CIGS NCs to P3HT, solvent effects on thin film morphologies, interface between P3HT/CIGS NCs and post-production annealing of devices were investigated, and the best performance of photovoltaic devices was measured under AM 1.5 simulated solar illumination (100 mW/cm2).
The Lyme disease spirochete Borrelia burgdorferi induces inflammation and apoptosis in cells from dorsal root ganglia
Authors: Ramesh Geeta , Santana-Gould Lenay , Inglis Fiona M , England John D , Philipp Mario T 
Published: July 2013

AbstractBackgroundLyme neuroborreliosis (LNB), caused by the spirocheteBorrelia burgdorferi, affects both the peripheral and the central nervous systems. Radiculitis or nerve root inflammation, which can cause pain, sensory loss, and weakness, is the most common manifestation of peripheral LNB in humans. We previously reported that rhesus monkeys infected withB.burgdorferidevelop radiculitis as well as inflammation in the dorsal root ganglia (DRG), with elevated levels of neuronal and satellite glial cell apoptosis in the DRG. We hypothesized thatB.burgdorferiinduces inflammatory mediators in glial and neuronal cells and that this inflammatory milieu precipitates glial and neuronal apoptosis.MethodsTo model peripheral neuropathy in LNB we incubated normal rhesus DRG tissue explants with liveB.burgdorferi ex vivoand identified immune mediators, producer cells, and verified the presence ofB.burgdorferiin tissue sections by immunofluorescence staining and confocal microscopy. We also set up primary cultures of DRG cells from normal adult rhesus macaques and incubated the cultures with liveB.burgdorferi. Culture supernatants were subjected to multiplex ELISA to detect immune mediators, while the cells were evaluated for apoptosis by thein situTUNEL assay. A role for inflammation in mediating apoptosis was assessed by evaluating the above phenomena in the presence and absence of various concentrations of the anti-inflammatory drug dexamethasone. As Schwann cells ensheath the dorsal roots of the DRG, we evaluated the potential of liveB.burgdorferito induce inflammatory mediators in human Schwann cell (HSC) cultures.ResultsRhesus DRG tissue explants exposed to liveB.burgdorferishowed localization of CCL2 and IL-6 in sensory neurons, satellite glial cells and Schwann cells while IL-8 was seen in satellite glial cells and Schwann cells. LiveB.burgdorferiinduced elevated levels of IL-6, IL-8 and CCL2 in HSC and DRG cultures and apoptosis of sensory neurons. Dexamethasone reduced the levels of immune mediators and neuronal apoptosis in a dose dependent manner.ConclusionIn this model,B.burgdorferiinduced an inflammatory response and neuronal apoptosis of DRG. These pathophysiological processes could contribute to peripheral neuropathy in LNB.
Reduction of microglial activity in a model of multiple sclerosis by dipyridamole
Authors: Sloka Scott , Metz Luanne M , Hader Walter , Starreveld Yves , Yong V Wee 
Published: July 2013

AbstractBackgroundDespite extensive and persistent activation of microglia in multiple sclerosis (MS), microglia inhibitors have not yet been identified for treatment of the disorder. We sought to identify medications already in clinical use that could inhibit the activation of microglia. On the basis of the reported inhibitory effects of dipyridamole on phosphodiesterase activity that result in the production of various anti-inflammatory outcomes, we selected it for study. Dipyridamole is used clinically for secondary prevention in stroke. In this study, dipyridamole was examined using microglia in culture and in the mouse model of MS, experimental autoimmune encephalomyelitis (EAE).ResultsWe found that dipyridamole attenuated the elevation of several cytokines and chemokines in human microglia caused by Toll-like receptor stimulation. Morphological characteristics of activated microglia in culture were also normalized by dipyridamole. In mice, dipyridamole decreased the clinical severity of EAE and reduced microglial activity and other histological indices of EAE in the spinal cord.ConclusionsDipyridamole is an inhibitor of microglia activation and may have a role in MS and other neurological conditions to attenuate microglial activity.
Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection
Authors: Jost Stephanie , Moreno-Nieves Uriel Y , Garcia-Beltran Wilfredo F , Rands Keith , Reardon Jeff , Toth Ildiko , Piechocka-Trocha Alicja , Altfeld Marcus , Addo Marylyn M 
Published: July 2013

Abstract

Background
Natural killer (NK) cells constitutively express high levels of Tim-3, an immunoregulatory molecule recently proposed to be a marker for mature and functional NK cells. Whether HIV-1 infection modulates the expression of Tim-3 on NK cells, or the levels of its ligand Galectin-9 (Gal-9), and how signaling through these molecules affects the NK cell response to HIV-1 remains inadequately understood.

Results
We analyzed Tim-3 and Gal-9 expression in a cohort of 85 individuals with early and chronic HIV-1 infection, and in 13 HIV-1 seronegative control subjects. HIV-1 infection was associated with reduced expression of Tim-3 on NK cells, which was normalized by HAART. Plasma concentrations of Gal-9 were higher in HIV-1-infected individuals than in healthy individuals. Interestingly, Gal-9 expression in immune cells was significantly elevated in early infection, with monocytes and dendritic cells displaying the highest expression levels, which correlated with HIV-1 viral loads. In vitro, Gal-9 triggered Tim-3 downregulation on NK cells as well as NK cell activation.

Conclusions
Our data suggest that high expression levels of Gal-9 during early HIV-1 infection can lead to enhanced NK cell activity, possibly allowing for improved early control of HIV-1. In contrast, persistent Gal-9 production might impair Tim-3 activity and contribute to NK cell dysfunction in chronic HIV-1 infection.
‘Huang Qi Elixir’ for proteinuria in patients with diabetic nephropathy: a study protocol for a randomized controlled pilot trial
Authors: Tu Xiang , Liu Fang , Jordan James B , Ye Xue Feng , Fu Ping , Wang Fei , Zhong Sen 
Published: July 2013

Abstract

Background
Diabetic nephropathy (DN) is the major complication of diabetes; proteinuria is the hall mark of DN. Currently, the treatment for proteinuria is mainly limited to angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). According to Traditional Chinese Medicine (TCM) theory, Chinese medicinals ‘securing essence and tonifying the kidney’ may be appropriate for proteinuria. The most promising Chinese medicinals and formulae are introduced in the present study to form a potent formula for DN proteinuria. To make oral administration convenient, the formula will be processed in the form of granules.

Methods/design
A randomized, multi-center pilot trial will be conducted. Forty eight participants with DN will be randomly assigned to one of four treatment groups:
1. A granule group, at 10 grams, three times daily (G10 group, n = 12);
2. A granule group, at 20 grams, three times daily (G20 group, n = 12);
3. A decoction group (D group, n = 12); and
4. An irbesartan group (Aprovel group, n = 12).
The following outcome measures will be used: the percentage change of the albumin-to-creatinine ratio; and the changes in serum creatinine, glomerular filtration rate, fasting plasma glucose and hemoglobulin from baseline to the end of the trial.

Discussion
It is notable that most published clinical trials which assessed the efficacy of TCM on DN were of poor methodology and, therefore, their results have been invalidated. It is necessary to carry out well-designed clinical trials to provide sound evidence. The present trial is a study with potentially great value, for it will provide the parameters for future randomized, placebo-controlled, clinical trials with large sample sizes.

Trial registration
The trial is registered on the Chinese Clinical Trial Registry: ChiCTR-TRC-12002718 (http://www.chictr.org/cn/proj/show.aspx?proj=3820).
Medicinal plants used for the treatment of various skin disorders by a rural community in northern Maputaland, South Africa
Authors: De Wet Helene , Nciki Sibongile , van Vuuren Sandy F 
Published: July 2013

Abstract
Background
Skin diseases have been of major concern recently due to their association with the Human Immunodeficiency Virus and Acquired Immunity Deficiency Syndrome (HIV/AIDS). The study area (northern Maputaland) has the highest HIV infection rate in South Africa, which made them more prone to a wide range of skin conditions. Fungal infections due to the hot climate and overcrowding households are common in this area, as well as burn accidents due to the use of wood as the major fuel for cooking. It is known that the lay people in this area depend on medicinal plants for their primary health care. However no survey has been done in northern Maputaland to document the medicinal plants used to treat various skin disorder.

Methods
Interviews were undertaken at 80 homesteads, using structured questionnaires. The focus was on plants used for dermatological conditions and information regarding vernacular plant names, plant parts used, preparation (independently and in various combinations) and application was collected.

Results
A total of 87 lay people, both male (22%) and female (78%) were interviewed on their knowledge of medicinal plants used to treat disorders of the skin. Forty-seven plant species from 35 families were recorded in the present survey for the treatment of 11 different skin disorders including abscesses, acne, burns, boils, incisions, ringworm, rashes, shingles, sores, wounds and warts. When searching the most frequently used scientific databases (ScienceDirect, Scopus and Pubmed), nine plant species (Acacia burkei, Brachylaena discolor, Ozoroa engleri, Parinari capensis, subsp. capensis, Portulacaria afra, Sida pseudocordifolia, Solanum rigescens, Strychnos madagascariensis and Drimia delagoensis) were found to be recorded for the first time globally as a treatment for skin disorders. Fourteen plant combinations were used. Surprisingly, the application of enema’s was frequently mentioned.

Conclusions
The preference of traditional medicine over allopathic medicine by most of the interviewees strengthens previous studies on the importance that traditional medicine can have in the primary health care system in this rural community. Studies to validate the potential of these plants independently and in their various combinations is underway to provide insight into the anti-infective role of each plant.
A synonymous change, p.Gly16Gly in MECP2 Exon 1, causes a cryptic splice event in a Rett syndrome patient
Authors: Sheikh Taimoor I , Mittal Kirti , Willis Mary J , Vincent John B 
Published: July 2013

Abstract

Background
Mutations in MECP2 are the main cause of Rett Syndrome. To date, no pathogenic synonymous MECP2 mutation has yet been identified. Here, we investigated a de novo synonymous variant c.48C>T (p.Gly16Gly) identified in a girl presenting with a typical RTT phenotype.

Methods

In silico analyses to predict the effects of sequence variation on mRNA splicing were employed, followed by sequencing and quantification of lymphocyte mRNAs from the subject for splice variants MECP2_E1 and MECP2_E2.

Results
Analysis of mRNA confirmed predictions that this synonymous mutation activates a splice-donor site at an early position in exon 1, leading to a deletion (r.[=, 48_63del]), codon frameshift and premature stop codon (p.Glu17Lysfs*16) for MECP2_E1. For MECP2_E2, the same premature splice site is used, but as this is located in the 5′untranslated region, no effect on the amino acid sequence is predicted. Quantitative analysis that specifically measured this cryptic splice variant also revealed a significant decrease in the quantity of the correct MECP2_E1 transcript, which indicates that this is the etiologically significant mutation in this patient.

Conclusion
These findings suggest that synonymous variants of MECP2 as well as other known disease genes—and de novo variants in particular— should be re-evaluated for potential effects on splicing.