bluuebunny/crossref_metadata_2025_split huggingface dataset:
Orai1 (CRACM1) is the platelet SOC channel and essential for pathological thrombus formation
Authors: Braun Attila , Varga-Szabo David , Kleinschnitz Christoph , Pleines Irina , Bender Markus , Austinat Madeleine , Bösl Michael , Stoll Guido , Nieswandt Bernhard 
Published: October 2008

Abstract
Platelet activation and aggregation at sites of vascular injury are essential for primary hemostasis, but are also major pathomechanisms underlying myocardial infarction and stroke. Changes in [Ca2+]i are a central step in platelet activation. In nonexcitable cells, receptor-mediated depletion of intracellular Ca2+ stores triggers Ca2+ entry through store-operated calcium (SOC) channels. STIM1 has been identified as an endoplasmic reticulum (ER)–resident Ca2+ sensor that regulates store-operated calcium entry (SOCE) in immune cells and platelets, but the identity of the platelet SOC channel has remained elusive. Orai1 (CRACM1) is the recently discovered SOC (CRAC) channel in T cells and mast cells but its role in mammalian physiology is unknown. Here we report that Orai1 is strongly expressed in human and mouse platelets. To test its role in blood clotting, we generated Orai1-deficient mice and found that their platelets display severely defective SOCE, agonist-induced Ca2+ responses, and impaired activation and thrombus formation under flow in vitro. As a direct consequence, Orai1 deficiency in mice results in resistance to pulmonary thromboembolism, arterial thrombosis, and ischemic brain infarction, but only mild bleeding time prolongation. These results establish Orai1 as the long-sought platelet SOC channel and a crucial mediator of ischemic cardiovascular and cerebrovascular events.
Brachyspira pilosicoli bloodstream infections: Case report and review of the literature
Authors: Bait-Merabet Lilia , Thille Arnaud , Legrand Patrick , Brun-Buisson Christian , Cattoir Vincent 
Published: October 2008

Abstract

Brachyspira pilosicoli is the etiologic agent of human and animal intestinal spirochetosis and is rarely implicated as a cause of bacteremia. Here, we describe the case of a B. pilosicoli spirochetemia in a 53-year-old male patient suffering from cardiogenic shock. This fastidious bacterium was isolated from blood, likely after translocation from the intestinal tract. Blood cultures were positive after 5 days of incubation (one day after the patient's death), highlighting the problem of the recovery of such type of fastidious bacterium. Identification was achieved by molecular methods (16S rRNA sequencing). A review of the English literature found only 8 cases of bacteremia caused by B. pilosicoli, mostly in immunocompromised or critically ill patients. Finally, difficulties in rapid and accurate diagnosis of B. pilosicoli bloodstream infections, in vitro antimicrobial susceptibility of human clinical isolates, and therapeutic options are discussed.
Rationale for prostaglandin I2in bone marrow oedema – from theory to application
Authors: Jäger Marcus , Tillmann Frank Peter , Thornhill Thomas S , Mahmoudi Marcus , Blondin Dirk , Hetzel Gerd Rüdiger , Zilkens Christoph , Krauspe Rüdiger 
Published: October 2008

Abstract
Introduction
Bone marrow oedema (BME) and avascular osteonecrosis (AVN) are disorders of unclear origin. Although there are numerous operative and non-operative treatments for AVN, pain management in patients with AVN remains challenging. Prostaglandins play an important role in inflammatory responses and cell differentiation. It is thought that prostaglandin I2 ([PGI2] or synonoma prostacyclin) and its analogues promote bone regeneration on a cellular or systemic level. The purpose of this study was to assess the curative and symptomatic efficacy of the prostacyclin analogue iloprost in BME and AVN patients.

Method
We are reporting on 50 patients (117 bones) affected by BME/AVN who were treated with iloprost. Pain levels before, during and 3 and 6 months after iloprost application were evaluated by a visual analogue scale (VAS). The short form(SF)-36 health survey served to judge general health status before and after treatment. Harris Hip Score (HHS) and Knee Society Score (KSS) were performed as functional scores and MRI and X-rays before and 3 and 6 months after iloprost application served as objective parameters for morphological changes of the affected bones.

Results
We found a significant improvement in pain, functional and radiological outcome in BME and early AVN stages after iloprost application, whereas patients with advanced AVN stages did not benefit from iloprost infusions. Mean pain level decreased from 5.26 (day 0) to 1.63 (6 months) and both HHS and KSS increased during follow-up. Moreover, the SF-36 increased from 353.2 (day 0) to 560.5 points (6 months). We found a significant decrease in BME on MRI scans after iloprost application.

Conclusions
In addition to other drugs, iloprost may be an alternative substance which should be considered in the treatment of BME/AVN-associated pain.
Arabidopsis iba response5 Suppressors Separate Responses to Various Hormones
Authors: Strader Lucia C , Monroe-Augustus Melanie , Rogers Kristen C , Lin Grace L , Bartel Bonnie 
Published: October 2008

Abstract
Auxin controls numerous plant growth processes by directing cell division and expansion. Auxin-response mutants, including iba response5 (ibr5), exhibit a long root and decreased lateral root production in response to exogenous auxins. ibr5 also displays resistance to the phytohormone abscisic acid (ABA). We found that the sar3 suppressor of auxin resistant1 (axr1) mutant does not suppress ibr5 auxin-response defects, suggesting that screening for ibr5 suppressors might reveal new components important for phytohormone responsiveness. We identified two classes of Arabidopsis thaliana mutants that suppressed ibr5 resistance to indole-3-butyric acid (IBA): those with restored responses to both the auxin precursor IBA and the active auxin indole-3-acetic acid (IAA) and those with restored response to IBA but not IAA. Restored IAA sensitivity was accompanied by restored ABA responsiveness, whereas suppressors that remained IAA resistant also remained ABA resistant. Some suppressors restored sensitivity to both natural and synthetic auxins; others restored responsiveness only to auxin precursors. We used positional information to determine that one ibr5 suppressor carried a mutation in PLEIOTROPIC DRUG RESISTANCE9 (PDR9/ABCG37/At3g53480), which encodes an ATP-binding cassette transporter previously implicated in cellular efflux of the synthetic auxin 2,4-dichlorophenoxyacetic acid.
Selection for Environmental Variation: A Statistical Analysis and Power Calculations to Detect Response
Authors: Ibáñez-Escriche Noelia , Sorensen Daniel , Waagepetersen Rasmus , Blasco Agustín 
Published: October 2008

AbstractData from uterine capacity in rabbits (litter size) were analyzed to determine whether the environmental variance was partly genetically determined. The fit of a classical homogeneous variance mixed linear (HOM) model and that of a genetically structured heterogeneous variance mixed linear (HET) model were compared. Various methods to assess the quality of fit favor the HET model. The posterior mean (95% posterior interval) of the additive genetic variance affecting the environmental variance was 0.16 (0.10; 0.25) and the corresponding number for the coefficient of correlation between genes affecting mean and variance was −0.74 (−0.90;−0.52). It is argued that stronger support for the HET model than that derived from statistical analysis of data would be provided by a successful selection experiment designed to modify the environmental variance. A simple selection criterion is suggested (average squared deviation from the mean of repeated records within individuals) and its predicted response and variance under the HET model are derived. This is used to determine the appropriate size and length of a selection experiment designed to change the environmental variance. Results from the analytical expressions are compared with those obtained using simulation. There is good agreement provided selection intensity is not intense.
A Simple Formula for Obtaining Markedly Improved Mutation Rate Estimates
Authors: Gerrish Philip 
Published: October 2008

AbstractIn previous work by M. E. Jones and colleagues, it was shown that mutation rate estimates can be improved and corresponding confidence intervals tightened by following a very easy modification of the standard fluctuation assay: cultures are grown to a larger-than-usual final density, and mutants are screened for in only a fraction of the culture. Surprisingly, this very promising development has received limited attention, perhaps because there has been no efficient way to generate the predicted mutant distribution to obtain non-moment-based estimates of the mutation rate. Here, the improved fluctuation assay discovered by Jones and colleagues is made amenable to quantile-based, likelihood, and other Bayesian methods by a simple recursion formula that efficiently generates the entire mutant distribution after growth and dilution. This formula makes possible a further protocol improvement: grow cultures as large as is experimentally possible and severely dilute before plating to obtain easily countable numbers of mutants. A preliminary look at likelihood surfaces suggests that this easy protocol adjustment gives markedly improved mutation rate estimates and confidence intervals.
Unstable RNAi Effects Through Epigenetic Silencing of an Inverted Repeat Transgene in Chlamydomonas reinhardtii
Authors: Yamasaki Tomohito , Miyasaka Hitoshi , Ohama Takeshi 
Published: October 2008

Abstract
RNA interferences in the unicellular green alga, Chlamydomonas reinhardtii, can be silenced. We have used the silencing of a transgene (aadA) that confers resistance to spectinomycin to investigate the mechanisms responsible for silencing by an artificial inverted repeat (IR) of the aadA gene. The IR construct provided strong silencing, but the RNAi efficiency varied among subclones of a single RNAi-transformed strain with successive cell divisions. Northern blot analyses revealed an inverse correlation between the copy number of the hairpin RNA and the spectinomycin resistance of the subclones. There is an inverse correlation between the efficiency of RNAi and the frequency of methylated CpG (*CpG) in the silenced region. No significant methylated cytosine was observed in the target aadA gene, which suggests the absence of RNA-directed DNA methylation in trans. Several experiments suggest the existence of an intrinsic IR sequence-dependent but a transcription-independent DNA methylation system in C. reinhardtii. The correlation between the *CpG levels and the IR transcript implies the existence of IR DNA-dependent DNA methylation. Treatment of RNAi-induced cells with a histone deacetylase inhibitor, Trichostatin A, rapidly increased the amount of the hairpin RNA and suggests that transcription of the silencer construct was repressed by *CpG-related silencing mechanisms.
Recruitment of Saccharomyces cerevisiae Dnl4–Lif1 Complex to a Double-Strand Break Requires Interactions With Yku80 and the Xrs2 FHA Domain
Authors: Palmbos Phillip L , Wu Dongliang , Daley James M , Wilson Thomas E 
Published: October 2008

Abstract
Nonhomologous end joining (NHEJ) in yeast depends on eight different proteins in at least three different functional complexes: Yku70–Yku80 (Ku), Dnl4–Lif1–Nej1 (DNA ligase IV), and Mre11–Rad50–Xrs2 (MRX). Interactions between these complexes at DNA double-strand breaks (DSBs) are poorly understood but critical for the completion of repair. We previously identified two such contacts that are redundantly required for NHEJ, one between Dnl4 and the C terminus of Yku80 and one between the forkhead-associated (FHA) domain of Xrs2 and the C terminus of Lif1. Here, we first show that mutation of the Yku80 C terminus did not impair Ku binding to DSBs, supporting specificity of the mutant defect to the ligase interaction. We next show that the Xrs2–Lif1 interaction depends on Xrs2 FHA residues (R32, S47, R48, and K75) analogous to those known in other proteins to contact phosphorylated threonines. Two potential target threonines in Lif1 (T417 and T387) were inferred by identifying regions similar to a site in the human Lif1 homolog, XRCC4, known to be bound by the FHA domain of polynucleotide kinase. Mutating these threonines, especially T417, abolished the Xrs2–Lif1 interaction and impaired NHEJ epistatically with Xrs2 FHA mutation. Combining mutations that selectively disable the Yku80–Dnl4 and Xrs2–Lif1 interactions abrogated both NHEJ and DNA ligase IV recruitment to a DSB. The collected results indicate that the Xrs–Lif1 and Yku80–Dnl4 interactions are important for formation of a productive ligase–DSB intermediate.
A Self-Renewal Program Controls the Expansion of Genetically Unstable Cancer Stem Cells in Pluripotent Stem Cell-Derived Tumors
Authors: Conway Anne E. , Lindgren Anne , Galic Zoran , Pyle April D. , Wu Hong , Zack Jerome A. , Pelligrini Matteo , Teitell Michael A. , Clark Amander T. 
Published: October 2008

AbstractHuman germ cell tumors are often metastatic, presumably due to distal site tumor growth by cancer stem cells. To determine whether cancer stem cells can be identified in a transplantation model of testicular germ cell tumor, we transplanted murine embryonic germ cells (EGCs) into the testis of adult severe combined immunodeficient mice. Transplantation resulted in a locally invasive solid tumor, with a cellular component that generated secondary tumors upon serial transplantation. The secondary tumors were invariably metastatic, a feature not observed in the primary tumors derived from EGCs. To characterize the differences between EGCs and the tumor-derived stem cells, we performed karyotype and microarray analysis. Our results show that generation of cancer stem cells is associated with the acquisition of nonclonal genomic rearrangements not found in the originating population. Furthermore, pretreatment of EGCs with a potent inhibitor of self-renewal, retinoic acid, prevented tumor formation and the emergence of these genetically unstable cancer stem cells. Microarray analysis revealed that EGCs and first- and second-generation cancer stem cells were highly similar; however, approximately 1,000 differentially expressed transcripts could be identified corresponding to alterations in oncogenes and genes associated with motility and development. Combined, the data suggest that the activation of oncogenic pathways in a cellular background of genetic instability, coupled with an inherent ability to self-renew, is involved in the acquisition of metastatic behavior in the cancer stem cell population of tumors derived from pluripotent cells.
The Role of Lmx1a in the Differentiation of Human Embryonic Stem Cells into Midbrain Dopamine Neurons in Culture and After Transplantation into a Parkinson's Disease Model
Authors: Cai Jingli , Donaldson Angela , Yang Ming , German Michael S. , Enikolopov Grigori , Iacovitti Lorraine 
Published: October 2008

AbstractRecent studies have provided important insight into the homeoprotein LIM homeobox transcription factor 1α (Lmx1a) and its role in the commitment of cells to a midbrain dopamine (mDA) fate in the developing mouse. We show here that Lmx1a also plays a pivotal role in the mDA differentiation of human embryonic stem (hES) cells. Thus, as indicated by small interfering RNA experiments, the transient early expression of Lmx1a is necessary for the coordinated expression of all other dopamine (DA)-specific phenotypic traits as hES cells move from multipotent human neural progenitor cells (hNPs) to more restricted precursor cells in vitro. Moreover, only Lmx1a-specified hNPs have the potential to differentiate into bona fide mDA neurons after transplantation into the 6-hydroxydopamine-treated rat striatum. In contrast, cortical human neuronal precursor cells (HNPCs) and mouse subventricular zone cells do not express Lmx1a or become mDA neurons even when placed in an environment that fosters their DA differentiation in vitro or in vivo. These findings suggest that Lmx1a may be critical to the development of mDA neurons from hES cells and that, along with other key early DA markers (i.e., Aldh1a1), may prove to be extremely useful for the selection of appropriately staged and suitably mDA-specified hES cells for cell replacement in Parkinson's disease.
Periodontal Bacterial Profiles in Pregnant Women: Response to Treatment and Associations With Birth Outcomes in the Obstetrics and Periodontal Therapy (OPT) Study
Authors: Novak M. John , Novak Karen F. , Hodges James S. , Kirakodu Sreenatha , Govindaswami Meera , DiAngelis Anthony , Buchanan William , Papapanou Panos N. , Michalowicz Bryan S. 
Published: October 2008

Background: A recent clinical trial (Obstetrics and Periodontal Therapy [OPT] Study) demonstrated that periodontal therapy during pregnancy improved periodontal outcomes but failed to impact preterm birth. The present study evaluated seven target bacteria, Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia (previously T. forsythensis), Prevotella intermedia, Campylobacter rectus, and Fusobacterium nucleatum, in subgingival dental plaque of pregnant women in the OPT Study and their association with birth outcomes.Methods: Pregnant women were randomly assigned to receive periodontal treatment before 21 weeks’ gestation or after delivery. Subgingival plaque was sampled at baseline (13 to 16 weeks; 6 days of gestation) and at 29 to 32 weeks. We analyzed subgingival plaque samples from women who experienced fetal loss, delivered a live preterm infant (preterm women), or delivered a full‐term infant (full‐term women). Samples were analyzed using quantitative polymerase chain reaction. Associations between preterm birth and bacterial counts and percentages were tested using multiple linear regression.Results: No significant differences were observed at baseline between preterm and full‐term women for any measured bacterial species or group of species, after accounting for multiple comparisons. Changes in bacterial counts and proportions during pregnancy also were not associated with birth outcomes. In full‐term and preterm women, periodontal therapy significantly reduced (P <0.01) counts of all target species except for A. actinomycetemcomitans.Conclusions: In pregnant women with periodontitis, non‐surgical periodontal therapy significantly reduced levels of periodontal pathogens. Baseline levels of selected periodontal pathogens or changes in these bacteria resulting from therapy were not associated with preterm birth.
Evaluation of Mandibular Posterior Single Implants With Two Different Surfaces: A 5‐Year Comparative Study
Authors: Jung Ui‐Won , Choi Jung‐Yoo , Kim Chang‐Sung , Cho Kyoo‐Sung , Chai Jung‐Kiu , Kim Chong‐Kwan , Choi Seong‐Ho 
Published: October 2008

Background: Anatomic and biomechanical limitations can jeopardize successful single implantation in the mandibular posterior area. To overcome the limitations, the design and the surface of the fixtures were modified. This study evaluated the cumulative survival rate (CSR) of mandibular molars replaced with a sand‐blasted, large‐grit, acid‐etched (SLA) single implant or an anodized (ANO) single implant and examined associated factors, such as the surface treatment, position, and length and diameter of the implants.Methods: One hundred ninety‐three single implants restored with an SLA implant and 112 single implants restored with an ANO implant in the mandibular molar area were selected from subjects who had visited the Department of Periodontology, Dental Hospital of Yonsei University, from March 2001 through June 2006. In the SLA group, 123 and 70 implants were placed in the first and second molar area, respectively. In the ANO group, 55 and 57 implants were placed in the first and second molar area, respectively. The 1‐ to 6‐year CSR of the SLA and ANO groups was calculated using the life‐table analysis. In addition, associated factors, such as the surface treatment, position, and length and diameter of the implants, were compared and analyzed using the χ2 test (P <0.05).Results: Two of 193 implants in the SLA group failed, giving a CSR of 98.96%; four of 112 ANO implants failed, giving a CSR of 96.43%. There were no significant differences with regard to the surface treatment, position, and length and diameter of the implants.Conclusions: Despite the anatomic and biomechanical limitation in the mandibular posterior area, mandibular posterior single implants showed a high CSR during the observation period. Mandibular posterior single implants can be an effective and reliable treatment modality that is not affected by the surface treatment, position, or length and diameter of the implant.
Early Wound Healing Following One‐Stage Dental Implant Placement With and Without Antibiotic Prophylaxis: A Pilot Study
Authors: Khoury Samer B. , Thomas Leslie , Walters John D. , Sheridan John F. , Leblebicioglu Binnaz 
Published: October 2008

Background: One‐stage implant placement has clinically acceptable treatment outcomes. Among other advantages, it may allow investigation of early wound healing. The purpose of this pilot study was to determine whether peri‐implant crevicular fluid (PICF) can be used to detect early changes around implants placed with one‐stage surgical protocol following 1 week of healing.Methods: Twenty subjects (11 males and nine females; aged 22 to 72 years; two smokers) were included. Exclusion criteria were allergies to amoxicillin and systemic conditions that may affect healing. Subjects had a healthy periodontium and needed a single implant; eight received antibiotic prophylaxis, and 12 served as controls. Clinical healing was evaluated with plaque and gingival indices (PI and GI, respectively). Gingival crevicular fluid (GCF) from the surgical site was obtained prior to the surgery, whereas PICF was collected at the 1‐week visit. Enzyme‐linked immunosorbent assay was used to determine GCF/PICF interleukin (IL)‐1β and −8 concentrations. Peripheral blood and GCF antibiotic levels were measured by high‐performance liquid chromatography.Results: Postoperative PI and GI were slightly increased. Total GCF and PICF volumes did not show a significant difference between appointments. There was an increase in PICF IL‐1β and −8 levels at 1 week postoperatively. Mean amoxicillin serum concentration was 5.1 ± 2 μg/ml at 1 to 4 hours following the initial dose, whereas GCF amoxicillin levels were below the limit of detection. Antibiotic prophylaxis had a modest effect on clinical indices (PI and GI) and no appreciable effect on biomarkers.Conclusions: PICF content can be studied as early as 1 week following one‐stage implant placement. The results raise doubts regarding the clinical usefulness of amoxicillin prophylaxis.