bluuebunny/crossref_metadata_2025_split huggingface dataset:
P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation
Authors: Avery-Kiejda Kelly A , Bowden Nikola A , Croft Amanda J , Scurr Lyndee L , Kairupan Carla F , Ashton Katie A , Talseth-Palmer Bente A , Rizos Helen , Zhang Xu D , Scott Rodney J , Hersey Peter 
Published: May 2011

Abstract

Background
Metastatic melanoma represents a major clinical problem. Its incidence continues to rise in western countries and there are currently no curative treatments. While mutation of the P53 tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of P53 in melanoma is uncommon; however, its function often appears abnormal.

Methods
In this study whole genome bead arrays were used to examine the transcript expression of P53 target genes in extracts from 82 melanoma metastases and 6 melanoma cell lines, to provide a global assessment of aberrant P53 function. The expression of these genes was also examined in extracts derived from diploid human melanocytes and fibroblasts.

Results
The results indicated that P53 target transcripts involved in apoptosis were under-expressed in melanoma metastases and melanoma cell lines, while those involved in the cell cycle were over-expressed in melanoma cell lines. There was little difference in the transcript expression of P53 target genes between cell lines with null/mutant P53 compared to those with wild-type P53, suggesting that altered expression in melanoma was not related to P53 status. Similarly, down-regulation of P53 by short-hairpin RNA (shRNA) had limited effect on P53 target gene expression in melanoma cells, whereas there were a large number of P53 target genes whose mRNA expression was significantly altered by P53 inhibition in melanocytes. Analysis of whole genome gene expression profiles indicated that the ability of P53 to regulate genes involved in the cell cycle was significantly reduced in melanoma cells. Moreover, inhibition of P53 in melanocytes induced changes in gene expression profiles that were characteristic of melanoma cells and resulted in increased proliferation. Conversely, knockdown of P53 in melanoma cells resulted in decreased proliferation.

Conclusions
These results indicate that P53 target genes involved in apoptosis and cell cycle regulation are aberrantly expressed in melanoma and that this aberrant functional activity of P53 may contribute to the proliferation of melanoma.
Real-time visualization of heterotrimeric G protein Gq activation in living cells
Authors: Adjobo-Hermans Merel JW , Goedhart Joachim , van Weeren Laura , Nijmeijer Saskia , Manders Erik MM , Offermanns Stefan , Gadella Theodorus WJ 
Published: May 2011

Abstract

Background
Gq is a heterotrimeric G protein that plays an important role in numerous physiological processes. To delineate the molecular mechanisms and kinetics of signalling through this protein, its activation should be measurable in single living cells. Recently, fluorescence resonance energy transfer (FRET) sensors have been developed for this purpose.

Results
In this paper, we describe the development of an improved FRET-based Gq activity sensor that consists of a yellow fluorescent protein (YFP)-tagged Gγ2 subunit and a Gαq subunit with an inserted monomeric Turquoise (mTurquoise), the best cyan fluorescent protein variant currently available. This sensor enabled us to determine, for the first time, the kon (2/s) of Gq activation. In addition, we found that the guanine nucleotide exchange factor p63RhoGEF has a profound effect on the number of Gq proteins that become active upon stimulation of endogenous histamine H1 receptors. The sensor was also used to measure ligand-independent activation of the histamine H1 receptor (H1R) upon addition of a hypotonic stimulus.

Conclusions
Our observations reveal that the application of a truncated mTurquoise as donor and a YFP-tagged Gγ2 as acceptor in FRET-based Gq activity sensors substantially improves their dynamic range. This optimization enables the real-time single cell quantification of Gq signalling dynamics, the influence of accessory proteins and allows future drug screening applications by virtue of its sensitivity.
Yellow fever virus envelope protein expressed in insect cells is capable of syncytium formation in lepidopteran cells and could be used for immunodetection of YFV in human sera
Authors: Barros Maria CES , Galasso Tatiane GCM , Chaib Antônio JM , Degallier Nicolas , Nagata Tatsuya , Ribeiro Bergmann M 
Published: May 2011

Abstract

Background
Yellow fever is an haemorrhagic disease caused by a virus that belongs to the genus Flavivirus (Flaviviridae family) and is transmitted by mosquitoes. Among the viral proteins, the envelope protein (E) is the most studied one, due to its high antigenic potencial. Baculovirus are one of the most popular and efficient eukaryotic expression system. In this study a recombinant baculovirus (vSynYFE) containing the envelope gene (env) of the 17D vaccine strain of yellow fever virus was constructed and the recombinant protein antigenicity was tested.

Results
Insect cells infected with vSynYFE showed syncytium formation, which is a cytopathic effect characteristic of flavivirus infection and expressed a polypeptide of around 54 kDa, which corresponds to the expected size of the recombinant E protein. Furthermore, the recombinant E protein expression was also confirmed by fluorescence microscopy of vSynYFE-infected insect cells. Total vSynYFE-infected insect extracts used as antigens detected the presence of antibodies for yellow fever virus in human sera derived from yellow fever-infected patients in an immunoassay and did not cross react with sera from dengue virus-infected patients.

Conclusions
The E protein expressed by the recombinant baculovirus in insect cells is antigenically similar to the wild protein and it may be useful for different medical applications, from improved diagnosis of the disease to source of antigens for the development of a subunit vaccine.
Growth and development of Gnathostoma spinigerum (Nematoda: Gnathostomatidae) larvae in Mesocyclops aspericornis (Cyclopoida: Cyclopidae)
Authors: Janwan Penchom , Intapan Pewpan M , Sanpool Oranuch , Sadaow Luxkhana , Thanchomnang Tongjit , Maleewong Wanchai 
Published: May 2011

Abstract

Background

Gnathostoma spinigerum larva is pathogenic, causing gnathostomiasis in humans and certain animals, and is prevalent mainly in Asia. Growth and development of Gnathostoma spinigerum larvae in the cyclopoid copepod Mesocyclops aspericornis, the first intermediate host, were examined.

Results
When newly hatched, ensheathed second-stage larvae (L2) were ingested by M. aspericornis, they immediately appeared exsheathed in the stomach of M. aspericornis. They then penetrated the stomach wall and entered the body cavity, where they immediately metamorphosed to a stunted form with the body length/width ratio equal to the early third-stage larvae (EL3) up to 2 h after being ingested. During metamorphosis, the anterior spine-like structure of L2 transformed into unequal transparent lips. The larvae moulted into EL3 in the body cavity of the copepod at around day 5-7 post-infection. Minute cuticular striations were seen on the whole body, with prominent single-pointed spines on the anterior part of the body. The head bulb had four rows of hooklets and two lateral trilobed lips. The size of EL3 in copepods continuously increased towards day 12 and showed a negative correlation to their density per copepod (R = -0.881, P < 0.05 for body length, and R = -0.906, P < 0.05 for body width).

Conclusions
The results revealed for the first time that M. aspericornis, one of the most abundant freshwater copepods in Thailand, is a suitable first intermediate host for G. spinigerum. High susceptibility of M. aspericornis suggests its importance for the maintenance of the life cycle of G. spinigerum in Thailand.
Race–ethnicity as an effect modifier of the association between HbAlc and mortality in U.S. adults without diagnosed diabetes
Authors: Kehl Katharina G , Findeisen Hannes M , Fardo David W , Bruemmer Dennis , Mannino David M , Sanderson Wayne T 
Published: May 2011

ObjectiveHbAlc is increasingly appreciated as a risk factor for all-cause and cardiovascular disease (CVD) mortality in the non-diabetic population. In this study, we investigated the association between HbAlc and mortality with a particular focus on the impact of race–ethnicity.DesignCohort study.MethodsWe analyzed the association between HbAlc and all-cause and CVD mortality in 12 698 non-diabetic adults 20 years or older from the Third National Health and Nutrition Examination Survey using separate models for people of different race–ethnicity.ResultsIn our stratified analyses, higher non-diabetic HbAlc levels were associated with all-cause and CVD mortality in non-Hispanic whites only. In this group, compared with HbAlc values of 5.0–<5.35%, the multivariable-adjusted estimated hazard ratios (est. HR) with 95% confidence interval (CI) for all-cause mortality were 1.21 (0.92, 1.58), 1.22 (1.03, 1.45), 1.29 (1.14, 1.47), and 1.4 (1.02, 1.87) for HbAlc levels of <5.0, 5.35–<5.7, 5.7–<6.5, and 6.5% or greater respectively. The association did not reach significance in Mexican–Americans (est. HR (95% CI): 1.77 (1.08, 2.91), 0.81 (0.56, 1.19), 1.16 (0.86, 1.57), and 1.4 (0.83, 2.36)). No association was observed in non-Hispanic blacks: 1.13 (0.91, 1.39), 0.81 (0.61, 1.08), 0.84 (0.69, 1.03), and 0.94 (0.67, 1.33). Results were similar for CVD mortality.ConclusionsOur data suggest limitations of HbAlc as a risk factor for all-cause and cardiovascular mortality across race–ethnic populations.
Estimated Glomerular Filtration Rate Is a Poor Predictor of Concentration for a Broad Range of Uremic Toxins
Authors: Eloot Sunny , Schepers Eva , Barreto Daniela V. , Barreto Fellype C. , Liabeuf Sophie , Van Biesen Wim , Verbeke Francis , Glorieux Griet , Choukroun Gabriel , Massy Ziad , Vanholder Raymond 
Published: May 2011

Summary

Background and objectives
The degree of chronic kidney disease (CKD) is currently expressed in terms of GFR, which can be determined directly or estimated according to different formulas on the basis of serum creatinine and/or cystatin C measurements (estimated GFR [eGFR]). The purpose of this study was to investigate whether eGFR values are representative for uremic toxin concentrations in patients with different degrees of CKD.

Design, setting, participants, & measurements
Associations between eGFR based on serum cystatin C and different uremic solutes (mol wt range 113 to 240 D; determined by colorimetry, HPLC, or ELISA) were evaluated in 95 CKD patients not on dialysis (CKD stage 2 to 5). The same analysis was also applied for six other eGFR formulas.

Results
There was a substantial disparity in fits among solutes. In linear regression, explained variance of eGFR was extremely low for most solutes, with eGFR > 0.4 only for creatinine. The other eGFR formulations gave comparably disappointing results with regard to their association to uremic solutes. Relative similarity in R
2 values per solute for the different eGFR values and the strong disparity in values between solutes suggest that the differences in R
2 are mainly due to discrepancies in solute handling apart from GFR.

Conclusions
eGFR is poorly associated with concentrations of all studied uremic toxins in patients with different degrees of CKD, correlates differently with each individual solute, and can thus not be considered representative for evaluating the accumulation of solutes in the course of CKD.
Is Coronary Artery Calcification Associated with Vertebral Bone Density in Nondialyzed Chronic Kidney Disease Patients?
Authors: Filgueira Agostinho , Carvalho Aluizio Barbosa , Tomiyama Cristiane , Higa Andrea , Rochitte Carlos E. , Santos Raul D. , Canziani Maria Eugênia F. 
Published: May 2011

Summary

Background and objectives
Low bone mineral density and coronary artery calcification (CAC) are highly prevalent among chronic kidney disease (CKD) patients, and both conditions are strongly associated with higher mortality. The study presented here aimed to investigate whether reduced vertebral bone density (VBD) was associated with the presence of CAC in the earlier stages of CKD.

Design, setting, participants, & measurements
Seventy-two nondialyzed CKD patients (age 52 ± 11.7 years, 70% male, 42% diabetics, creatinine clearance 40.4 ± 18.2 ml/min per 1.73 m2) were studied. VBD and CAC were quantified by computed tomography.

Results
CAC > 10 Agatston units (AU) was observed in 50% of the patients (median 120 AU [interquartile range 32 to 584 AU]), and a calcification score ≥ 400 AU was found in 19% (736 [527 to 1012] AU). VBD (190 ± 52 Hounsfield units) correlated inversely with age (r = −0.41, P < 0.001) and calcium score (r = −0.31, P = 0.01), and no correlation was found with gender, creatinine clearance, proteinuria, lipid profile, mineral parameters, body mass index, and diabetes. Patients in the lowest tertile of VBD had expressively increased calcium score in comparison to the middle and highest tertile groups. In the multiple logistic regression analysis adjusting for confounding variables, low VBD was independently associated with the presence of CAC.

Conclusions
Low VBD was associated with CAC in nondialyzed CKD patients. The authors suggest that low VBD might constitute another nontraditional risk factor for cardiovascular disease in CKD.
Activation of Peroxisome Proliferator–Activated Receptor-β/-δ (PPAR-β/-δ) Ameliorates Insulin Signaling and Reduces SOCS3 Levels by Inhibiting STAT3 in Interleukin-6–Stimulated Adipocytes
Authors: Serrano-Marco Lucía , Rodríguez-Calvo Ricardo , El Kochairi Ilhem , Palomer Xavier , Michalik Liliane , Wahli Walter , Vázquez-Carrera Manuel 
Published: May 2011

OBJECTIVE
It has been suggested that interleukin (IL)-6 is one of the mediators linking obesity-derived chronic inflammation with insulin resistance through activation of STAT3, with subsequent upregulation of suppressor of cytokine signaling 3 (SOCS3). We evaluated whether peroxisome proliferator–activated receptor (PPAR)-β/-δ prevented activation of the IL-6-STAT3-SOCS3 pathway and insulin resistance in adipocytes.

RESEARCH DESIGN AND METHODS
Adipocytes and white adipose tissue from wild-type and PPAR-β/-δ-null mice were used to evaluate the effect of PPAR-β/-δ on the IL-6-STAT3-SOCS3 pathway.

RESULTS
First, we observed that the PPAR-β/-δ agonist GW501516 prevented both IL-6–dependent reduction in insulin-stimulated Akt phosphorylation and glucose uptake in adipocytes. In addition, this drug treatment abolished IL-6–induced SOCS3 expression in differentiated 3T3-L1 adipocytes. This effect was associated with the capacity of the drug to prevent IL-6–induced STAT3 phosphorylation on Tyr705 and Ser727 residues in vitro and in vivo. Moreover, GW501516 prevented IL-6–dependent induction of extracellular signal–related kinase (ERK)1/2, a serine-threonine-protein kinase involved in serine STAT3 phosphorylation. Furthermore, in white adipose tissue from PPAR-β/-δ–null mice, STAT3 phosphorylation (Tyr705 and Ser727), STAT3 DNA-binding activity, and SOCS3 protein levels were higher than in wild-type mice. Several steps in STAT3 activation require its association with heat shock protein 90 (Hsp90), which was prevented by GW501516 as revealed in immunoprecipitation studies. Consistent with this finding, the STAT3-Hsp90 association was enhanced in white adipose tissue from PPAR-β/-δ–null mice compared with wild-type mice.

CONCLUSIONS
Collectively, our findings indicate that PPAR-β/-δ activation prevents IL-6–induced STAT3 activation by inhibiting ERK1/2 and preventing the STAT3-Hsp90 association, an effect that may contribute to the prevention of cytokine-induced insulin resistance in adipocytes.
Retinol-Binding Protein 4 Is Associated With Prediabetes in Adults From the General Population
Authors: Meisinger Christa , Rückert Ina M. , Rathmann Wolfgang , Döring Angela , Thorand Barbara , Huth Cornelia , Kowall Bernd , Koenig Wolfgang 
Published: May 2011

OBJECTIVE
We examined the association between retinol-binding protein 4 (RBP4), a novel adipokine, and prediabetes (isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT], and combined IFG and IGT) in men and women aged 32–81 years.

RESEARCH DESIGN AND METHODS
The analysis was based on 2,614 participants without previously diagnosed diabetes and those with newly diagnosed diabetes of the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study, conducted from 2006 to 2008 in southern Germany. Plasma RBP4 was analyzed by immunonephelometry.

RESULTS
In logistic regression analysis, RBP4 levels in the fourth quartile versus the first quartile were significantly associated with prediabetes (i-IGT, i-IFG, and IFG/IGT; reference normal glucose tolerance) independent of known metabolic risk factors and lifestyle variables (odds ratio 1.63 [95% CI 1.17–2.27] after multivariable adjustment). Stratification by sex showed generally similar results.

CONCLUSIONS
RBP4 levels were associated with prediabetes in individuals from the general population. Prospective studies investigating the impact of RBP4 on the development of glucose intolerance are needed.
Indirect Evidences of Wildlife Activities in Shoals of Western Ghats, a Biodiversity Hotspots
Authors: Jain Manjari , Utpal Singha , Mukhopadhyay S. 
Published: May 2011

Indirect Evidences of Wildlife Activities in Shoals of Western Ghats, a Biodiversity HotspotsThe presence of wildlife fauna and its activities were ascertained with the density of the scat, dung and other markings or droppings of the wildlife abode therein. Attempt was made to find out spatial differences in the activities of the wildlife populations and to comment on the abundance of different preys and predators within shola forests of Western Ghat hill forests, a Biodiversity hotspot in India. An indirect sampling method, Transect Count Method, was employed to count dung/pellet group/scat and other markings in that area. Pachyderms were found to be mostly dominant in Varagaliar and Punnumala shola patches while scats of all the three important predators, viz., tiger (Panthera tigris tigris), Indian wild dog (Cuon alpinus) and leopard (Panthera pardus) were encountered only in Varagaliar shola. Greater abundance was recorded from Indira Gandhi Wildlife Sanctuary than Silent Valley National Park may be because of the restriction of animal movements in the former due to topographical barriers and its existence as isolated shola patches that led to a greater concentration of wild fauna in a relatively segregated forest cover.
Ecological assessment of wetland ecosystems of northern Kazakhstan on the basis of hydrochemistry and algal biodiversity
Authors: Barinova Sophia , Nevo Eibi , Bragina Tatiana 
Published: May 2011

Ecological assessment of wetland ecosystems of northern Kazakhstan on the basis of hydrochemistry and algal biodiversity
We studied diversity of algae and cyanobacteria in the wetlands of protected natural lakes with salinity ranging from 0.19 up to 32.7 in the arid/semiarid regions of Northern Kazakhstan. In plankton and periphyton of 34 lakes, we found 254 species belonging to 113 genera of 8 algal divisions. The diversity in arid regions is represented by widespread species of diatoms, green algae, and cyanobacteria in similar proportions. Alkaliphiles, among the indicators of acidification, and betamesosaprobionts, among the indicators of saprobity, predominated. The indices of saprobity in lakes varied from 1.47 to 2.7, reflecting low-trophic and low anthropogenically disturbed wetlands. Oligohalobes-indifferents are most common. Highly diverse algal communities were found irrespective of various levels of mineralization. As a consequence of aridization, salinity increase suppressed algal diversity. The mineralization was the most important variable defining the diversity levels, irrespective of the type and location of wetland lakes in the arid regions.
Shift of the western boundary of the distribution area of Micromeria cristata (Hampe) Griseb. and Steptorhamphus tuberosus (Jacq.) Grossh
Authors: Petrović Danka , Stešević Danijela 
Published: May 2011

Shift of the western boundary of the distribution area ofMicromeria cristata(Hampe) Griseb. andSteptorhamphus tuberosus(Jacq.) GrosshDuring field investigations of Mt Rumija, two new taxa for the flora of Montenegro were recorded:Micromeria cristata(Hampe) Griseb. andSteptorhamphus tuberosus(Jacq.) Grossh. From the phytogeographic point of view these data indicate a change in the distribution area of both taxa, which have shifted to the west. Ashort over-view of the taxonomic treatment of both genera is given.
Universal Tunable Current-Mode Biquad Employing Distributed Feedback Structure with MO-CCCII
Authors: Šotner Roman , Slezák Josef , Dostál Tomáš , Petržela Jiří 
Published: June 2011

Universal Tunable Current-Mode Biquad Employing Distributed Feedback Structure with MO-CCCIIOne possible application of the multiple-output electronically-tunable active building block as a universal filter with distributed feedback structure is presented. The suggested structure is less conventional than the well-known state-variable Kerwin-Huelsman-Newcomb but allows the same filter configurations with the similar properties. The major current-mode design approach disadvantage,ie, the necessity of multiple current outputs, is demonstrated. To date even a rather big line of the commercially available devices do not solve this problem. Some features of the active block used for modelling and transistor-level simulation are briefly discussed. The obvious chance for electronic tuning of the proposed filter is verified.
Angiographic features of “brain sag”
Authors: Alaraj Ali , Munson Troy , Herrera Sebastian R. , Aletich Victor , Charbel Fady T. , Amin-Hanjani Sepideh 
Published: May 2011

Object
Cerebrospinal fluid hypotension, or “brain sag,” is a recently described phenomenon most commonly seen following craniotomy for the clipping of ruptured aneurysms along with preoperative lumbar drain placement. The clinical features and CT findings have been previously described. Clinical presentation can be similar to and often mistaken for cerebral vasospasm. In this study, the authors report on the angiographic findings in patients with brain sag.

Methods
Five cases of brain sag were diagnosed (range 1–4 days) after the surgical treatment of ruptured aneurysms at the University of Illinois at Chicago. All patients met the clinical and CT criteria for brain sag. Admission cerebral angiograms and subsequent angiograms during symptoms of brain sag were obtained in all patients. In 3 patients, angiography was performed after the resolution of symptoms.

Results
In all 5 patients, the level of the basilar artery apex was displaced inferiorly with respect to the posterior clinoid processes during brain sag. This displacement was significant enough to create a noticeable kink in the basilar artery (“cobra sign”) in 3 patients. Other angiographic findings included foreshortening or kinking of the intracranial vertebral artery. In all patients, the posterior cerebral arteries were displaced medially and inferiorly. Three patients were treated for simultaneous severe radiological vasospasm. In 4 patients, the brain sag was recognized, and the patients' conditions improved when they were placed flat or in the Trendelenburg position, at times combined with an epidural blood patch. Patients with follow-up angiography studies after the symptoms had resolved displayed a reversal of the angiographic features.

Conclusions
Brain sag appears to be associated with characteristic angiographic features. Recognizing these features may help to diagnose brain sag as the cause of neurological deterioration in this patient population.