bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trichostatin A treatment of cloned mouse embryos improves constitutive heterochromatin remodeling as well as developmental potential to term
Authors: Maalouf Walid E , Liu Zichuan , Brochard Vincent , Renard Jean-Paul , Debey Pascale , Beaujean Nathalie , Zink Daniele 
Published: March 2009

Abstract

Background
Genome reprogramming in early mouse embryos is associated with nuclear reorganization and particular features such as the peculiar distribution of centromeric and pericentric heterochromatin during the first developmental stage. This zygote-specific heterochromatin organization could be observed both in maternal and paternal pronuclei after natural fertilization as well as in embryonic stem (ES) cell nuclei after nuclear transfer suggesting that this particular type of nuclear organization was essential for embryonic reprogramming and subsequent development.

Results
Here, we show that remodeling into a zygotic-like organization also occurs after somatic cell nuclear transfer (SCNT), supporting the hypothesis that reorganization of constitutive heterochromatin occurs regardless of the source and differentiation state of the starting material. However, abnormal nuclear remodeling was frequently observed after SCNT, in association with low developmental efficiency. When transient treatment with the histone deacetylase inhibitor trichostatin A (TSA) was tested, we observed improved nuclear remodeling in 1-cell SCNT embryos that correlated with improved rates of embryonic development at subsequent stages.

Conclusion
Together, the results suggest that proper organization of constitutive heterochromatin in early embryos is involved in the initial developmental steps and might have long term consequences, especially in cloning procedures.
Whole genome surveys of rice, maize and sorghum reveal multiple horizontal transfers of the LTR-retrotransposon Route66 in Poaceae
Authors: Roulin Anne , Piegu Benoit , Fortune Philippe M , Sabot François , D'Hont Angélique , Manicacci Domenica , Panaud Olivier 
Published: March 2009

Abstract

Background
Horizontal transfers (HTs) refer to the transmission of genetic material between phylogenetically distant species. Although most of the cases of HTs described so far concern genes, there is increasing evidence that some involve transposable elements (TEs) in Eukaryotes. The availability of the full genome sequence of two cereal species, (i.e. rice and Sorghum), as well as the partial genome sequence of maize, provides the opportunity to carry out genome-wide searches for TE-HTs in Poaceae.

Results
We have identified an LTR-retrotransposon, that we named Route66, with more than 95% sequence identity between rice and Sorghum. Using a combination of in silico and molecular approaches, we are able to present a substantial phylogenetic evidence that Route66 has been transferred horizontally between Panicoideae and several species of the genus Oryza. In addition, we show that it has remained active after these transfers.

Conclusion
This study constitutes a new case of HTs for an LTR-retrotransposon and we strongly believe that this mechanism could play a major role in the life cycle of transposable elements. We therefore propose to integrate classe I elements into the previous model of transposable element evolution through horizontal transfers.
Ancient diversification of eukaryotic MCM DNA replication proteins
Authors: Liu Yuan , Richards Thomas A , Aves Stephen J 
Published: March 2009

Abstract

Background
Yeast and animal cells require six mini-chromosome maintenance proteins (Mcm2-7) for pre-replication complex formation, DNA replication initiation and DNA synthesis. These six individual MCM proteins form distinct heterogeneous subunits within a hexamer which is believed to form the replicative helicase and which associates with the essential but non-homologous Mcm10 protein during DNA replication. In contrast Archaea generally only possess one MCM homologue which forms a homohexameric MCM helicase. In some eukaryotes Mcm8 and Mcm9 paralogues also appear to be involved in DNA replication although their exact roles are unclear.

Results
We used comparative genomics and phylogenetics to reconstruct the diversification of the eukaryotic Mcm2-9 gene family, demonstrating that Mcm2-9 were formed by seven gene duplication events before the last common ancestor of the eukaryotes. Mcm2-7 protein paralogues were present in all eukaryote genomes studied suggesting that no gene loss or functional replacements have been tolerated during the evolutionary diversification of eukaryotes. Mcm8 and 9 are widely distributed in eukaryotes and group together on the MCM phylogenetic tree to the exclusion of all other MCM paralogues suggesting co-ancestry. Mcm8 and Mcm9 are absent in some taxa, including Trichomonas and Giardia, and appear to have been secondarily lost in some fungi and some animals. The presence and absence of Mcm8 and 9 is concordant in all taxa sampled with the exception of Drosophila species. Mcm10 is present in most eukaryotes sampled but shows no concordant pattern of presence or absence with Mcm8 or 9.

Conclusion
A multifaceted and heterogeneous Mcm2-7 hexamer evolved during the early evolution of the eukaryote cell in parallel with numerous other acquisitions in cell complexity and prior to the diversification of extant eukaryotes. The conservation of all six paralogues throughout the eukaryotes suggests that each Mcm2-7 hexamer component has an exclusive functional role, either by a combination of unique lock and key interactions between MCM hexamer subunits and/or by a range of novel side interactions. Mcm8 and 9 evolved early in eukaryote cell evolution and their pattern of presence or absence suggests that they may have linked functions. Mcm8 is highly divergent in all Drosophila species and may not provide a good model for Mcm8 in other eukaryotes.
Safety and effectiveness of colistin compared with tobramycin for multi-drug resistant Acinetobacter baumannii infections
Authors: Gounden Ronald , Bamford Colleen , van Zyl-Smit Richard , Cohen Karen , Maartens Gary 
Published: March 2009

Abstract

Background
Nosocomial infections due to multi-drug resistant Acinetobacter baumannii are often treated with colistin, but there are few data comparing its safety and efficacy with other antimicrobials.

Methods
A retrospective cohort study of patients treated with colistin or tobramycin for A. baumannii infections in intensive care units (ICUs) at Groote Schuur hospital. Colistin was used for A. baumannii isolates which were resistant to all other available antimicrobials. In the tobramycin group, 53% of the isolates were only susceptible to tobramycin and colistin. We assessed ICU mortality, nephrotoxicity and time to the first negative culture.

Results
32 patients, with similar admission APACHE scores and serum creatinine, were treated with each antimicrobial. There were no significant differences between the colistin and tobramycin groups in ICU mortality (p = 0.54), nephrotoxicity (p = 0.67), change in creatinine from baseline to highest subsequent value (p = 0.11) and time to microbiological clearance (p = 0.75). The hazard ratio for total in-hospital survival in patients treated with colistin compared to tobramycin was 0.43 (95% CI 0.19 to 0.99).

Conclusion
Our study suggests that colistin and tobramycin have similar risks of nephrotoxicity and are equally efficacious. Colistin is an acceptable antibiotic for the treatment of A. baumanii infections when the organism is resistant to other available antimicrobials.
APRIL is overexpressed in cancer: link with tumor progression
Authors: Moreaux Jérôme , Veyrune Jean-Luc , De Vos John , Klein Bernard 
Published: March 2009

Abstract

Background
BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia.

Methods
We compared the expression of BAFF, APRIL, TACI and BAFF-R gene expression in 40 human tumor types – brain, epithelial, lymphoid, germ cells – to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.

Results
We found significant overexpression of TACI in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, BAFF and APRIL are overexpressed in many cancers and we show that APRIL expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans.

Conclusion
Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.
From bench to bedside: current and future applications of molecular profiling in renal cell carcinoma
Authors: Arsanious Androu , Bjarnason Georg A , Yousef George M 
Published: March 2009

AbstractAmong the adult population, renal cell carcinoma (RCC) constitutes the most prevalent form of kidney neoplasm. Unfortunately, RCC is relatively asymptomatic and there are no tumor markers available for diagnostic, prognostic or predictive purposes. Molecular profiling, the global analysis of gene and protein expression profiles, is an emerging promising tool for new biomarker identification in RCC. In this review, we summarize the existing knowledge on RCC regarding clinical presentation, treatment options, and tumor marker status. We present a general overview of the more commonly used approaches for molecular profiling at the genomic, transcriptomic and proteomic levels. We also highlight the emerging role of molecular profiling as not only revolutionizing the process of new tumor marker discovery, but also for providing a better understanding of the pathogenesis of RCC that will pave the way towards new targeted therapy discovery. Furthermore, we discuss the spectrum of clinical applications of molecular profiling in RCC in the current literature. Finally, we highlight some of the potential challenging that faces the era of molecular profiling and its transition into clinical practice, and provide an insight about the future perspectives of molecular profiling in RCC.
Local increase in trapezius muscle oxygenation during and after acupuncture
Authors: Ohkubo Masaki , Hamaoka Takafumi , Niwayama Masatugu , Murase Norio , Osada Takuya , Kime Ryotaro , Kurosawa Yuko , Sakamoto Ayumi , Katsumura Toshihito 
Published: March 2009

Abstract

Purpose
This study aimed to compare the trapezius muscle blood volume and oxygenation in the stimulation region and in a distant region in the same muscle during acupuncture stimulation (AS). We hypothesized that AS provokes a localized increase in muscle blood volume and oxygenation in the stimulation region.

Methods
Two sets of near-infrared spectrometer (NIRS) probes, with 40-mm light-source detector spacing, were placed on the right trapezius muscle, with a 50-mm distance between the probes. Changes in muscle oxygenation (oxy-Hb) and blood volume (t-Hb) in stimulation and distant regions (50 mm away from the stimulation point) were measured using NIRS. Nine healthy acupuncture-experienced subjects were chosen as the experimental (AS) group, and 10 healthy acupuncture-experienced subjects were chosen for the control (no AS) group. Measurements began with a 3-min rest period, followed by "Jakutaku" (AS) for 2 min, and recovery after stimulation.

Results
There was a significant increase in oxy-Hb (60.7 μM at maximum) and t-Hb (48.1 μM at maximum) in the stimulation region compared to the distant region. In the stimulation region, a significant increase in oxy-Hb and t-Hb compared with the pre-stimulation level was first noted at 58.5 s and 13.5 s, respectively, after the onset of stimulation.

Conclusion
In conclusion, oxygenation and blood volume increased, indicating elevated blood flow to the small vessels, not in the distant region used in this study, but in the stimulation region of the trapezius muscle during and after a 2-min AS.
Biomarkers of HIV-1 associated dementia: proteomic investigation of sera
Authors: Wiederin Jayme , Rozek Wojciech , Duan Fenghai , Ciborowski Pawel 
Published: March 2009

Abstract

Background
New, more sensitive and specific biomarkers are needed to support other means of clinical diagnosis of neurodegenerative disorders. Proteomics technology is widely used in discovering new biomarkers. There are several difficulties with in-depth analysis of human plasma/serum, including that there is no one proteomic platform that can offer complete identification of differences in proteomic profiles. Another set of problems is associated with heterogeneity of human samples in addition intrinsic variability associated with every step of proteomic investigation. Validation is the very last step of proteomic investigation and it is very often difficult to validate potential biomarker with desired sensitivity and specificity. Even though it may be possible to validate a differentially expressed protein, it may not necessarily prove to be a valid diagnostic biomarker.

Results
In the current study we report results of proteomic analysis of sera from HIV-infected individuals with or without cognitive impairment. Application of SELDI-TOF analysis followed by weak cation exchange chromatography and 1-dimensional electrophoresis led to discovery of gelsolin and prealbumin as differentially expressed proteins which were not detected in this cohort of samples when previously investigated by 2-dimensional electrophoresis with Difference Gel Electrophoresis technology.

Conclusion
Validation using western-blot analysis led us to conclude that relative change of the levels of these proteins in one patient during a timeframe might be more informative, sensitive and specific than application of average level estimated based on an even larger cohort of patients.
Training health care workers to promote HIV services for patients with tuberculosis in the Democratic Republic of Congo
Authors: Driessche Koen Vanden , Sabue Mulangu , Dufour Wendy , Behets Frieda , Van Rie Annelies 
Published: March 2009

Abstract

Background
HIV counseling and testing, HIV prevention and provision of HIV care and support are essential activities to reduce the burden of HIV among patients with TB, and should be integrated into routine TB care.

Methods
The development of training materials to promote HIV services for TB patients involved the definition of target health care workers (HCWs); identification of required tasks, skills and knowledge; review of international guidelines; and adaptation of existing training materials for voluntary counseling and testing, prevention of mother-to-child transmission of HIV, and management of opportunistic infections (OIs). Training effectiveness was assessed by means of questionnaires administered pre- and post-training, by correlating post-training results of HCWs with the centre's HIV testing acceptance rates, and through participatory observations at the time of on-site supervisory visits and monthly meetings.

Results
Pre-training assessment identified gaps in basic knowledge of HIV epidemiology, the link between TB and HIV, interpretation of CD4 counts, prevention and management of OIs, and occupational post-exposure prophylaxis (PEP). Opinions on patients' rights and confidentiality varied. Mean test results increased from 72% pre-training to 87% post-training (p < 0.001). Important issues regarding HIV epidemiology and PEP remained poorly understood post-training. Mean post-training scores of clinic's HCWs were significantly correlated with the centre's HIV testing acceptance rates (p = 0.01). On-site supervisory visits and monthly meetings promoted staff motivation, participatory problem solving and continuing education. Training was also used as an opportunity to improve patient-centred care and HCWs' communication skills.

Conclusion
Many HCWs did not possess the knowledge or skills necessary to integrate HIV activities into routine care for patients with TB. A participatory approach resulted in training materials that fulfilled local needs.
RAGE (Receptor for Advanced Glycation Endproducts), RAGE Ligands, and their role in Cancer and Inflammation
Authors: Sparvero Louis J , Asafu-Adjei Denise , Kang Rui , Tang Daolin , Amin Neilay , Im Jaehyun , Rutledge Ronnye , Lin Brenda , Amoscato Andrew A , Zeh Herbert J , Lotze Michael T 
Published: March 2009

AbstractThe Receptor for Advanced Glycation Endproducts [RAGE] is an evolutionarily recent member of the immunoglobulin super-family, encoded in the Class III region of the major histocompatability complex. RAGE is highly expressed only in the lung at readily measurable levels but increases quickly at sites of inflammation, largely on inflammatory and epithelial cells. It is found either as a membrane-bound or soluble protein that is markedly upregulated by stress in epithelial cells, thereby regulating their metabolism and enhancing their central barrier functionality. Activation and upregulation of RAGE by its ligands leads to enhanced survival. Perpetual signaling through RAGE-induced survival pathways in the setting of limited nutrients or oxygenation results in enhanced autophagy, diminished apoptosis, and (with ATP depletion) necrosis. This results in chronic inflammation and in many instances is the setting in which epithelial malignancies arise. RAGE and its isoforms sit in a pivotal role, regulating metabolism, inflammation, and epithelial survival in the setting of stress. Understanding the molecular structure and function of it and its ligands in the setting of inflammation is critically important in understanding the role of this receptor in tumor biology.
Nitric Oxide Activates ATP-Sensitive Potassium Channels in Mammalian Sensory Neurons: Action by Direct S-Nitrosylation
Authors: Kawano Takashi , Zoga Vasiliki , Kimura Masakazu , Liang Mei-Ying , Wu Hsiang-En , Gemes Geza , McCallum J Bruce , Kwok Wai-Meng , Hogan Quinn H , Sarantopoulos Constantine D 
Published: March 2009

Background ATP-sensitive potassium (KATP) channels in neurons regulate excitability, neurotransmitter release and mediate protection from cell-death. Furthermore, activation of KATP channels is suppressed in DRG neurons after painful-like nerve injury. NO-dependent mechanisms modulate both KATP channels and participate in the pathophysiology and pharmacology of neuropathic pain. Therefore, we investigated NO modulation of KATP channels in control and axotomized DRG neurons. Results Cell-attached and cell-free recordings of KATP currents in large DRG neurons from control rats (sham surgery, SS) revealed activation of KATP channels by NO exogenously released by the NO donor SNAP, through decreased sensitivity to [ATP]i. This NO-induced KATP channel activation was not altered in ganglia from animals that demonstrated sustained hyperalgesia-type response to nociceptive stimulation following spinal nerve ligation. However, baseline opening of KATP channels and their activation induced by metabolic inhibition was suppressed by axotomy. Failure to block the NO-mediated amplification of KATP currents with specific inhibitors of sGC and PKG indicated that the classical sGC/cGMP/ PKG signaling pathway was not involved in the activation by SNAP. NO-induced activation of KATP channels remained intact in cell-free patches, was reversed by DTT, a thiol-reducing agent, and prevented by NEM, a thiol-alkylating agent. Other findings indicated that the mechanisms by which NO activates KATP channels involve direct S-nitrosylation of cysteine residues in the SUR1 subunit. Specifically, current through recombinant wild-type SUR1/Kir6.2 channels expressed in COS7 cells was activated by NO, but channels formed only from truncated isoform Kir6.2 subunits without SUR1 subunits were insensitive to NO. Further, mutagenesis of SUR1 indicated that NO-induced KATP channel activation involves interaction of NO with residues in the NBD1 of the SUR1 subunit. Conclusion NO activates KATP channels in large DRG neurons via direct S-nitrosylation of cysteine residues in the SUR1 subunit. The capacity of NO to activate KATP channels via this mechanism remains intact even after spinal nerve ligation, thus providing opportunities for selective pharmacological enhancement of KATP current even after decrease of this current by painful-like nerve injury.
Characterization of NF-Kb-Mediated Inhibition of Catechol-O-Methyltransferase
Authors: Tchivileva Inna E , Nackley Andrea G , Qian Li , Wentworth Sean , Conrad Matthew , Diatchenko Luda B 
Published: March 2009

BackgroundCatechol- O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Specifically, low COMT activity is associated with heightened pain perception and development of musculoskeletal pain in humans as well as increased experimental pain sensitivity in rodents.ResultsWe report that the proinflammatory cytokine tumor necrosis factor α (TNFα) downregulates COMT mRNA and protein in astrocytes. Examination of the distal COMT promoter ( P2-COMT) reveals a putative binding site for nuclear factor κB (NF-κB), the pivotal regulator of inflammation and the target of TNFα. Cell culture assays and functional deletion analyses of the cloned P2-COMT promoter demonstrate that TNFα inhibits P2-COMT activity in astrocytes by inducing NF-κB complex recruitment to the specific κB binding site.ConclusionCollectively, our findings provide the first evidence for NF-κB-mediated inhibition of COMT expression in the central nervous system, suggesting that COMT contributes to the pathogenesis of inflammatory pain states.
Long term survivors with metastatic pancreatic adenocarcinoma treated with gemcitabine: a retrospective analysis
Authors: Goulart Bernardo HL , Clark Jeffrey W , Lauwers Gregory Y , Ryan David P , Grenon Nina , Muzikansky Alona , Zhu Andrew X 
Published: March 2009

AbstractBackgroundMetastatic pancreatic adenocarcinoma has a short median overall survival (OS) of 5–6 months. However, a subgroup of patients survives more than 1 year. We analyzed the survival outcomes of this subgroup and evaluated clinical and pathological factors that might affect survival durations.MethodsWe identified 20 patients with metastatic or recurrent pancreatic adenocarcinoma who received single-agent gemcitabine and had an OS longer than 1 year. Baseline data available after the diagnosis of metastatic or recurrent disease was categorized as: 1)clinical/demographic data(age, gender, ECOG PS, number and location of metastatic sites); 2)Laboratory data(Hematocrit, hemoglobin, glucose, LDH, renal and liver function and CA19-9); 3)Pathologic data(margins, nodal status and grade); 4)Outcomes data(OS, Time to Treatment Failure (TTF), and 2 year-OS). The lowest CA19-9 levels during treatment with gemcitabine were also recorded. We performed a univariate analysis with OS as the outcome variable.ResultsBaseline logarithm of CA19-9 and total bilirubin had a significant impact on OS (HR = 1.32 and 1.31, respectively). Median OS and TTF on gemcitabine were 26.9 (95% CI = 18 to 32) and 11.5 (95% CI = 9.0 to 14.3) months, respectively. Two-year OS was 56.4%, with 7 patients alive at the time of analysis.ConclusionA subgroup of patients with metastatic pancreatic cancer has prolonged survival after treatment with gemcitabine. Only bilirubin and CA 19-9 levels were predictive of longer survival in this population. Further analysis of potential prognostic and predictive markers of response to treatment and survival are needed.