bluuebunny/crossref_metadata_2025 huggingface dataset:
SND2, a NAC transcription factor gene, regulates genes involved in secondary cell wall development in Arabidopsis fibres and increases fibre cell area in Eucalyptus
Authors: Hussey Steven G , Mizrachi Eshchar , Spokevicius Antanas V , Bossinger Gerd , Berger Dave K , Myburg Alexander A
Published: December 2011

Background

NAC domain transcription factors initiate secondary cell wall biosynthesis inArabidopsisfibres and vessels by activating numerous transcriptional regulators and biosynthetic genes. NAC family memberSND2is an indirect target of a principal regulator of fibre secondary cell wall formation, SND1. A previous study showed that overexpression ofSND2produced a fibre cell-specific increase in secondary cell wall thickness inArabidopsisstems, and that the protein was able to transactivate thecellulose synthase8(CesA8) promoter. However, the full repertoire of genes regulated bySND2is unknown, and the effect of its overexpression on cell wall chemistry remains unexplored.

Results

We overexpressedSND2inArabidopsisand analyzed homozygous lines with regards to stem chemistry, biomass and fibre secondary cell wall thickness. A line showing upregulation ofCesA8was selected for transcriptome-wide gene expression profiling. We found evidence for upregulation of biosynthetic genes associated with cellulose, xylan, mannan and lignin polymerization in this line, in agreement with significant co-expression of these genes with nativeSND2transcripts according to public microarray repositories. Only minor alterations in cell wall chemistry were detected. Transcription factorMYB103, in addition toSND1, was upregulated inSND2-overexpressing plants, and we detected upregulation of genes encoding components of a signal transduction machinery recently proposed to initiate secondary cell wall formation. Several homozygous T4 and hemizygous T1 transgenic lines with pronouncedSND2overexpression levels revealed a negative impact on fibre wall deposition, which may be indirectly attributable to excessive overexpression rather than co-suppression. Conversely, overexpression ofSND2inEucalyptusstems led to increased fibre cross-sectional cell area.

Conclusions

This study supports a function forSND2in the regulation of cellulose and hemicellulose biosynthetic genes in addition of those involved in lignin polymerization and signalling. SND2 seems to occupy a subordinate but central tier in the secondary cell wall transcriptional network. Our results reveal phenotypic differences in the effect ofSND2overexpression between woody and herbaceous stems and emphasize the importance of expression thresholds in transcription factor studies.
Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial
Authors: Patel Jeetesh V , Hughes Elizabeth A , Lip Gregory YH , Gill Paramjit S
Published: December 2011

Background

Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk.

Methods/Design

The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner.

Discussion

It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities.

Trial registration

Current Controlled Trials ISRCTN02839188
The higher exercise intensity and the presence of allele I of ACE gene elicit a higher post-exercise blood pressure reduction and nitric oxide release in elderly women: an experimental study
Authors: Santana Hugo AP , Moreira Sérgio R , Neto Willson B , Silva Carla B , Sales Marcelo M , Oliveira Vanessa N , Asano Ricardo Y , Espíndola Foued S , Nóbrega Otávio T , Campbell Carmen SG , Simões Herbert G
Published: December 2011

Background

The absence of the I allele of the angiotensin converting enzyme (ACE) gene has been associated with higher levels of circulating ACE, lower nitric oxide (NO) release and hypertension. The purposes of this study were to analyze the post-exercise salivary nitrite (NO2
-) and blood pressure (BP) responses to different exercise intensities in elderly women divided according to their ACE genotype.

Methods

Participants (n = 30; II/ID = 20 and DD = 10) underwent three experimental sessions: incremental test - IT (15 watts workload increase/3 min) until exhaustion; 20 min exercise 90% anaerobic threshold (90% AT); and 20 min control session without exercise. Volunteers had their BP and NO2
- measured before and after experimental sessions.

Results

Despite both intensities showed protective effect on preventing the increase of BP during post-exercise recovery compared to control, post-exercise hypotension and increased NO2
- release was observed only for carriers of the I allele (p < 0.05).

Conclusion

Genotypes of the ACE gene may exert a role in post-exercise NO release and BP response.
Comparison of accuracy of fibrosis degree classifications by liver biopsy and non-invasive tests in chronic hepatitis C
Authors: Boursier Jérôme , Bertrais Sandrine , Oberti Frédéric , Gallois Yves , Fouchard-Hubert Isabelle , Rousselet Marie-Christine , Zarski Jean-Pierre , Calès Paul ,   multicentric studies Sniff 17, Vindiag 7, Metavar 4, ANRS HC EP 23 Fibrostar
Published: December 2011

Background

Non-invasive tests have been constructed and evaluated mainly for binary diagnoses such as significant fibrosis. Recently, detailed fibrosis classifications for several non-invasive tests have been developed, but their accuracy has not been thoroughly evaluated in comparison to liver biopsy, especially in clinical practice and for Fibroscan. Therefore, the main aim of the present study was to evaluate the accuracy of detailed fibrosis classifications available for non-invasive tests and liver biopsy. The secondary aim was to validate these accuracies in independent populations.

Methods

Four HCV populations provided 2,068 patients with liver biopsy, four different pathologist skill-levels and non-invasive tests. Results were expressed as percentages of correctly classified patients.

Results

In population #1 including 205 patients and comparing liver biopsy (reference: consensus reading by two experts) and blood tests, Metavir fibrosis (FM) stage accuracy was 64.4% in local pathologists vs. 82.2% (p < 10-3) in single expert pathologist. Significant discrepancy (≥ 2FM vs reference histological result) rates were: Fibrotest: 17.2%, FibroMeter2G: 5.6%, local pathologists: 4.9%, FibroMeter3G: 0.5%, expert pathologist: 0% (p < 10-3). In population #2 including 1,056 patients and comparing blood tests, the discrepancy scores, taking into account the error magnitude, of detailed fibrosis classification were significantly different between FibroMeter2G (0.30 ± 0.55) and FibroMeter3G (0.14 ± 0.37, p < 10-3) or Fibrotest (0.84 ± 0.80, p < 10-3). In population #3 (and #4) including 458 (359) patients and comparing blood tests and Fibroscan, accuracies of detailed fibrosis classification were, respectively: Fibrotest: 42.5% (33.5%), Fibroscan: 64.9% (50.7%), FibroMeter2G: 68.7% (68.2%), FibroMeter3G: 77.1% (83.4%), p < 10-3 (p < 10-3). Significant discrepancy (≥ 2 FM) rates were, respectively: Fibrotest: 21.3% (22.2%), Fibroscan: 12.9% (12.3%), FibroMeter2G: 5.7% (6.0%), FibroMeter3G: 0.9% (0.9%), p < 10-3 (p < 10-3).

Conclusions

The accuracy in detailed fibrosis classification of the best-performing blood test outperforms liver biopsy read by a local pathologist, i.e., in clinical practice; however, the classification precision is apparently lesser. This detailed classification accuracy is much lower than that of significant fibrosis with Fibroscan and even Fibrotest but higher with FibroMeter3G. FibroMeter classification accuracy was significantly higher than those of other non-invasive tests. Finally, for hepatitis C evaluation in clinical practice, fibrosis degree can be evaluated using an accurate blood test.
The MLH12101C>A (Q701K) variant increases the risk of gastric cancer in Chinese males
Authors: Zhi Wenxian , Xue Binshuang , Wang Lifeng , Xiao Nong , He Qiong , Wang Yaping , Fan Yimei
Published: December 2011

Background

Gastric cancer is one of the most common cancers affecting East Asians, and MLH1 could play a critical role during tumorigenesis in this condition.

Methods

Samples from 236 Chinese patients suffering from gastric cancer were screened for MLH1 germline mutations. Carrier frequencies of the mutations were compared between gastric cancer patients and 240 cancer-free controls. Bioinformatic analysis was used to predict the effect of these mutations on protein function and mRNA splicing.

Results

Six MLH1 sequence alterations were identified in gastric cancer patients including two promoter region substitutions, -93G>A and -28A>G, and four missense mutations 649C>T (R217C), 655A>G (I219V), 1151T>A (V384D) and 2101C>A (Q701K). Compared with the MLH1 2101CC genotype, the 2101CA genotype was associated with a risk of gastric cancer (OR = 8.42, 95% CI = 1.04-68.06) in males. Furthermore, the MLH1 2101C>A mutant was predicted by in silico analysis to affect exon splicing ability. Immunohistochemistry of one index patient carrying the MLH1 2101C>A mutation demonstrated a loss of MLH1 protein and normal expression of MSH2 and E-cadherin. No significant differences were demonstrated between cases and controls for the other five MLH1 variants but the data indicated an ethnic difference in the frequency of these variations between Eastern Asians and Western populations.

Conclusions

An ethnic-specific MLH1 mutation spectrum occurred in Chinese gastric cancer patients. The MLH1 2101C>A mutation could be a marker for susceptibility to gastric cancer, particularly in males.
Expression pattern of class I histone deacetylases in vulvar intraepithelial neoplasia and vulvar cancer: a tissue microarray study
Authors: Samartzis Nicolas , Imesch Patrick , Dedes Konstantin J , Samartzis Eleftherios P , Fedier André , Fink Daniel , Caduff Rosmarie , Fehr Mathias K
Published: December 2011

Background

Epigenetic regulation is an important mechanism leading to cancer initiation and promotion. Histone acetylation by histone deacetylases (HDACs) represents an important part of it. The development of HDAC inhibitors has identified the utility of HDACs as a therapeutic target. Little is known about the epigenetic regulation of vulvar intraepithelial neoplasia (VIN) and vulvar squamous cell cancer (VSCC). In this study, the expression of class I HDACs (HDAC 1, 2 and 3) was compared in a series of VIN and VSCC tissues.

Methods

A tissue micro array (TMA) with specimens from 106 patients with high-grade VIN and 59 patients with vulvar cancer was constructed. The expression of HDACs 1, 2 and 3 were analyzed with immunohistochemistry (IHC). The nuclear expression pattern was evaluated in terms of intensity and percentage of stained nuclei and was compared between vulvar preinvasive lesions and vulvar cancer.

Results

HDAC 2 expression was significantly higher in VIN than in VSCC (p < 0.001, Fisher's test). Also, 88.7% (n = 94/106) of VIN samples and only 54.5% (n = 31/57) of VSCC samples were scored at the maximum level. Conversely, HDAC 3 expression was significantly higher in VSCC (93%, 53/57) compared to VIN (73.6%, 78/106, p = 0.003), whereas only a small difference in the expression of HDAC 1 was found between these two entities of vulvar neoplasia.

Conclusions

These results suggest that epigenetic regulation plays a considerable role in the transformation of VIN to invasive vulvar neoplasia.
Acquisition of chemical recognition cues facilitates integration into ant societies
Authors: von Beeren Christoph , Schulz Stefan , Hashim Rosli , Witte Volker
Published: December 2011

Background

Social insects maintain the integrity of their societies by discriminating between colony members and foreigners through cuticular hydrocarbon (CHC) signatures. Nevertheless, parasites frequently get access to social resources, for example through mimicry of host CHCs among other mechanisms. The origin of mimetic compounds, however, remains unknown in the majority of studies (biosynthesis vs. acquisition). Additionally, direct evidence is scarce that chemical mimicry is indeed beneficial to the parasites (e.g., by improving social acceptance).

Results

In the present study we demonstrated that the kleptoparasitic silverfishMalayatelura ponerophilamost likely acquires CHCs directly from its host antLeptogenys distinguendaby evaluating the transfer of a stable-isotope label from the cuticle of workers to the silverfish. In a second experiment, we prevented CHC pilfering by separating silverfish from their host for six or nine days. Chemical host resemblance as well as aggressive rejection behaviour by host ants was then quantified for unmanipulated and previously separated individuals. Separated individuals showed reduced chemical host resemblance and they received significantly more aggressive rejection behaviour than unmanipulated individuals.

Conclusion

Our study clarifies the mechanism of chemical mimicry in a social insect parasite in great detail. It shows empirically for the first time that social insect parasites are able to acquire CHCs from their host. Furthermore, it demonstrates that the accuracy of chemical mimicry can be crucial for social insect parasites by enhancing social acceptance and, thus, allowing successful exploitation. We discuss the results in the light of coevolutionary arms races between parasites and hosts.
Practical considerations to guide development of access controls and decision support for genetic information in electronic medical records
Authors: Darcy Diana C , Lewis Eleanor T , Ormond Kelly E , Clark David J , Trafton Jodie A
Published: December 2011

Background

Genetic testing is increasingly used as a tool throughout the health care system. In 2011 the number of clinically available genetic tests is approaching 2,000, and wide variation exists between these tests in their sensitivity, specificity, and clinical implications, as well as the potential for discrimination based on the results.

Discussion

As health care systems increasingly implement electronic medical record systems (EMRs) they must carefully consider how to use information from this wide spectrum of genetic tests, with whom to share information, and how to provide decision support for clinicians to properly interpret the information. Although some characteristics of genetic tests overlap with other medical test results, there are reasons to make genetic test results widely available to health care providers and counterbalancing reasons to restrict access to these test results to honor patient preferences, and avoid distracting or confusing clinicians with irrelevant but complex information. Electronic medical records can facilitate and provide reasonable restrictions on access to genetic test results and deliver education and decision support tools to guide appropriate interpretation and use.

This paper will serve to review some of the key characteristics of genetic tests as they relate to design of access control and decision support of genetic test information in the EMR, emphasizing the clear need for health information technology (HIT) to be part of optimal implementation of genetic medicine, and the importance of understanding key characteristics of genetic tests when designing HIT applications.
Short-term effects of liraglutide on visceral fat adiposity, appetite, and food preference: a pilot study of obese Japanese patients with type 2 diabetes
Authors: Inoue Kana , Maeda Norikazu , Kashine Susumu , Fujishima Yuya , Kozawa Junji , Hiuge-Shimizu Aki , Okita Kohei , Imagawa Akihisa , Funahashi Tohru , Shimomura Iichiro
Published: December 2011

Background

To examine the effects of liraglutide, a glucagon-like peptide-1 (GLP-1) analogue, on visceral fat adiposity, appetite, food preference, and biomarkers of cardiovascular system in Japanese patients with type 2 diabetes.

Methods

The study subjects were 20 inpatients with type 2 diabetes treated with liraglutide [age; 61.2 ± 14.0 years, duration of diabetes; 16.9 ± 6.6 years, glycated hemoglobin (HbA1c); 9.1 ± 1.2%, body mass index (BMI); 28.3 ± 5.2 kg/m2, mean ± SD]. After improvement in glycemic control by insulin or oral glucose-lowering agents, patients were switched to liraglutide. We assessed the estimated visceral fat area (eVFA) by abdominal bioelectrical impedance analysis, glycemic control by the 75-g oral glucose tolerance test (OGTT) and eating behavior by the Japan Society for the Study of Obesity questionnaire.

Results

Treatment with liraglutide (dose range: 0.3 to 0.9 mg/day) for 20.0 ± 6.4 days significantly reduced waist circumference, waist/hip ratio, eVFA. It also significantly improved the scores of eating behavior, food preference and the urge for fat intake and tended to reduce scores for sense of hunger. Liraglutide increased serum C-peptide immunoreactivity and disposition index.

Conclusions

Short-term treatment with liraglutide improved visceral fat adiposity, appetite, food preference and the urge for fat intake in obese Japanese patients with type 2 diabetes.
Effect of Benzothiazole based conjugates in causing apoptosis by Regulating p53, PTEN and MAP Kinase proteins affecting miR-195a and miR-101-1
Authors: Pushpavalli SNCVL , Ramaiah M Janaki , Srinivas Ch , Mukhopadhya Debasmita , Aditya JL , Kumbhare Ravindra M , Bhadra Utpal , Bhadra Manika Pal
Published: December 2011

Background

Hepatocellular carcinoma (HCC) accounts for majority of liver cancers and is the leading cause of cancer related death in Asia. Like any other cancer, HCC develops when there is a mutation to the cellular machinery that causes the cell to replicate at a higher rate and results in the loss of apoptosis. Therefore, a delicate balance between the expression of various genes involved in proliferation and apoptosis decide the ultimate fate of the cell to undergo rapid proliferation (cancer) or cell death.

Results

The benzothiazole based compounds exhibited effective cytotoxicity at 4 μM concentration and have shown G1 cell cycle arrest with decrease in levels of G1 cell cycle proteins such as cyclin D1 and Skp2. Involvement of tumour suppressor proteins such as PTEN and p53 was studied. Interestingly these compounds displayed decrease in the phosphorylated forms of AKT, p38 MAPK and ERK1/2 which play a vital role in cell proliferation. Compounds have exhibited strong and significant effect on the expression of micro RNAs such as miR-195a & miR-101-1 which regulate hepatic cell proliferation.

Conclusions

The cell cycle arrest and apoptotic inducing nature of these compounds was revealed by FACS, BrdU cell proliferation and tunel assays. Compounds affected both tumour suppressor proteins as well as proteins that are involved in active cell proliferation. Micro RNAs whose target is Cyclin D1 such as miR-195a and miR-101-1 that is required for growth of hepatoma cells was drastically affected. These compounds caused apoptosis by activating caspase-3 and PARP.
Multivariate modelling with 1H NMR of pleural effusion in murine cerebral malaria
Authors: Ghosh Soumita , Sengupta Arjun , Sharma Shobhona , Sonawat Haripalsingh M
Published: December 2011

Background

Cerebral malaria is a clinical manifestation ofPlasmodium falciparuminfection. Although brain damage is the predominant pathophysiological complication of cerebral malaria (CM), respiratory distress, acute lung injury, hydrothorax/pleural effusion are also observed in several cases. Immunological parameters have been assessed in pleural fluid in murine models; however there are no reports of characterization of metabolites present in pleural effusion.

Methods

1H NMR of the sera and the pleural effusion of cerebral malaria infected mice were analyzed using principal component analysis, orthogonal partial least square analysis, multiway principal component analysis, and multivariate curve resolution.

Results

It has been observed that there was 100% occurrence of pleural effusion (PE) in the mice affected with CM, as opposed to those are non-cerebral and succumbing to hyperparasitaemia (NCM/HP). An analysis of1H NMR and SDS-PAGE profile of PE and serum samples of each of the CM mice exhibited a similar profile in terms of constituents. Multivariate analysis on these two classes of biofluids was performed and significant differences were detected in concentrations of metabolites. Glucose, creatine and glutamine contents were high in the PE and lipids being high in the sera. Multivariate curve resolution between sera and pleural effusion showed that changes in PE co-varied with that of serum in CM mice. The increase of glucose in PE is negatively correlated to the glucose in serum in CM as obtained from the result of multiway principal component analysis.

Conclusions

This study reports for the first time, the characterization of metabolites in pleural effusion formed during murine cerebral malaria. The study indicates that the origin of PE metabolites in murine CM may be the serum. The loss of the components like glucose, glutamine and creatine into the PE may worsen the situation of patients, in conjunction with the enhanced glycolysis, glutaminolysis and increased activity of creatine phophokinase which are already reported characteristic pathophysiological features of malaria.
Simulation of haemodynamic flow in head and neck cancer chemotherapy
Authors: Rhode Stephan , Paul Manosh C , Martens Eckhard , Campbell Duncan F
Published: December 2011

Background

In recent years, intra arterial chemotherapy has become an important component in head and neck cancer treatment. However, therapy success can vary significantly and consistent treatment guidelines are missing. The purpose of this study was to create a computer simulation of the chemical agent injection in the head and neck arteries to investigate the distribution and concentration of the chemical.

Methods

Realistic three dimensional patient specific geometry was created from image scan data. Pulsatile blood flow, turbulence, the chemical agent injection via a catheter, and the mixture between blood and the chemical were then simulated through the arterial network by computational fluid dynamics software.

Results

The results show a consistent chemical distribution throughout all the arteries and this is ineffective. In addition, due to high wall shear stress and turbulence at the inner bifurcation wall, serious complications during the treatment could occur, for instance haemolysis or thrombosis.

Conclusions

The modelled catheter position is insufficient to provide a high chemical agent concentration in the desired tumour feeding artery, which is vital for therapy success.
Fish polar lipids retard atherosclerosis in rabbits by down-regulating PAF biosynthesis and up-regulating PAF catabolism
Authors: Nasopoulou Constantina , Tsoupras Alexandros B , Karantonis Haralabos C , Demopoulos Constantinos A , Zabetakis Ioannis
Published: December 2011

Background

Platelet activating factor (PAF) has been proposed as a key factor and initial trigger in atherosclerosis. Recently, a modulation of PAF metabolism by bioactive food constituents has been suggested. In this study we investigated the effect of fish polar lipid consumption on PAF metabolism.

Results

The specific activities of four PAF metabolic enzymes; in leukocytes, platelets and plasma, and PAF concentration; either in blood cells or plasma were determined. Samples were acquired at the beginning and at the end of a previously conducted study in male New Zealand white rabbits that were fed for 45 days with atherogenic diet supplemented (group-B, n = 6) or not (group-A, n = 6) with gilthead sea bream (Sparus aurata) polar lipids.

The specific activity of PAF-Acetylhydrolase (PAF-AH); a catabolic enzyme of PAF, was decreased in rabbits' platelets of both A and B groups and in rabbits' leukocytes of group A (p < 0.05). On the other hand the specific activity of Lipoprotein-associated Phospholipase A2 (Lp-PLA2); the catabolic enzyme of PAF in plasma was increased in both A and B groups in both leukocytes and platelets (p < 0.05). PAF-cholinephosphotransferase (PAF-CPT); a biosynthetic enzyme of PAF showed increased specific activity only in rabbits' leukocytes of group A (p < 0.05). Neither of the two groups showed any change in Lyso-PAF-acetyltransferase (Lyso-PAF-AT) specific activity (p > 0.05). Free and bound PAF levels increased in group A while decreased in group B (p < 0.05).

Conclusions

Gilthead sea bream (Sparus aurata) polar lipids modulate PAF metabolism upon atherosclerotic conditions in rabbits leading to lower PAF levels and activity in blood of rabbits with reduced early atherosclerotic lesions compared to control group.
Impact of Chronic Kidney Disease on the Presence and Severity of Aortic Stenosis in Patients at High Risk for Coronary Artery Disease
Authors: Masuda Chiaki , Dohi Kaoru , Sakurai Yuko , Bessho Yuri , Fukuda Harumi , Fujii Shinobu , Sugimoto Tadafumi , Tanabe Masaki , Onishi Katsuya , Shiraki Katsuya , Ito Masaaki , Nobori Tsutomu
Published: December 2011

Objective

We evaluated the impact of chronic kidney disease (CKD) on the presence and severity of aortic stenosis (AS) in patients at high risk for coronary artery disease (CAD).

Methods

One hundred and twenty consecutive patients who underwent invasive coronary angiography were enrolled. Aortic valve area (AVA) was calculated by the continuity equation using transthoracic echocardiography, and was normalized by body surface area (AVA index).

Results

Among all 120 patients, 78% had CAD, 55% had CKD (stage 3: 81%; stage 4: 19%), and 34% had AS (AVA < 2.0cm2). Patients with AS were older, more often female, and had a higher frequency of CKD than those without AS, but the prevalence of CAD and most other coexisting conventional risk factors was similar between patients with and without AS. Multivariate linear regression analysis indicated that only CKD and CAD were independent determinants of AVA index with standardized coefficients of -0.37 and -0.28, respectively. When patients were divided into 3 groups (group 1: absence of CKD and CAD, n = 16; group 2: presence of either CKD or CAD, n = 51; and group 3: presence of both CKD and CAD, n = 53), group 3 had the smallest AVA index (1.19 ± 0.30*# cm2/m2, *p < 0.05 vs. group 1: 1.65 ± 0.32 cm2/m2, and #p < 0.05 vs. group 2: 1.43 ± 0.29* cm2/m2) and the highest peak velocity across the aortic valve (1.53 ± 0.41*# m/sec; *p < 0.05 vs. group 1: 1.28 ± 0.29 m/sec, and #p < 0.05 vs. group 2: 1.35 ± 0.27 m/sec).

Conclusion

CKD, even pre-stage 5 CKD, has a more powerful impact on the presence and severity of AS than other conventional risk factors for atherosclerosis in patients at high risk for CAD.
Fixed point theorems for mappings with condition (B)
Authors: Lin Lai-Jiu , Chuang Chih-Sheng , Yu Zenn-Tsun
Published: December 2011

In this article, a new type of mappings that satisfies condition (B) is introduced. We study Pazy's type fixed point theorems, demiclosed principles, and ergodic theorem for mappings with condition (B). Next, we consider the weak convergence theorems for equilibrium problems and the fixed points of mappings with condition (B).
Fixed point theorems for contraction mappings in modular metric spaces
Authors: Mongkolkeha Chirasak , Sintunavarat Wutiphol , Kumam Poom
Published: December 2011

In this article, we study and prove the new existence theorems of fixed points for contraction mappings in modular metric spaces.

AMS: 47H09; 47H10.
Sub-super solutions for (p-q) Laplacian systems
Authors: Haghaieghi Somayeh , Afrouzi Ghasem Alizadeh
Published: December 2011

In this work, we consider the system:

{

-

Δ
p

u
=
λ
[
g
(
x
)
a
(
u
)
+
f
(
v
)
]

in
Ω

-

Δ
q

v
=
λ
[
g
(
x
)
b
(
v
)
+
h
(
u
)
]

in
Ω

u

=

v

=
0

on
∂
Ω
,

where Ω is a bounded region in R

N
with smooth boundary ∂Ω, Δ
p
is the p-Laplacian operator defined by Δ
p

u = div (|∇u|
p-2∇u), p, q > 1 and g (x) is a C
1 sign-changing the weight function, that maybe negative near the boundary. f, h, a, b are C
1 non-decreasing functions satisfying a(0) ≥ 0, b(0) ≥ 0. Using the method of sub-super solutions, we prove the existence of weak solution.
A challenging diagnosis of alpha-1-antitrypsin deficiency: identification of a patient with a novel F/Null phenotype
Authors: Ringenbach Michael R , Banta Erin , Snyder Melissa R , Craig Timothy J , Ishmael Faoud T
Published: December 2011

Alpha-1-antitrypsin (A1AT) deficiency is a genetic disease characterized by low levels and/or function of A1AT protein. A1AT deficiency can result in the development of COPD, liver disease, and certain skin conditions. The disease can be diagnosed by demonstrating a low level of A1AT protein and genotype screening for S and Z mutations, which are the most common. However, there are many genetic variants in A1AT deficiency, and this screening may miss rarer cases, such as those caused by dysfunctional protein. We identified a patient with a previously unreported F/null phenotype that was missed by routine screening. This case highlights the wide variation in possible mutations, limitations in diagnostics, and the importance of combining clinical suspicion with measurement of protein levels, phenotypic analysis, and in appropriate cases expanded genetic analysis.
Closed-loop insulin delivery for treatment of type 1 diabetes
Authors: Elleri Daniela , Dunger David B , Hovorka Roman
Published: December 2011

Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence, and remains a serious chronic disorder with increased morbidity and mortality, and reduced quality of life. Technological innovations positively affect the management of type 1 diabetes. Closed-loop insulin delivery (artificial pancreas) is a recent medical innovation, aiming to reduce the risk of hypoglycemia while achieving tight control of glucose. Characterized by real-time glucose-responsive insulin administration, closed-loop systems combine glucose-sensing and insulin-delivery components. In the most viable and researched configuration, a disposable sensor measures interstitial glucose levels, which are fed into a control algorithm controlling delivery of a rapid-acting insulin analog into the subcutaneous tissue by an insulin pump. Research progress builds on an increasing use of insulin pumps and availability of glucose monitors. We review the current status of insulin delivery, focusing on clinical evaluations of closed-loop systems. Future goals are outlined, and benefits and limitations of closed-loop therapy contrasted. The clinical utility of these systems is constrained by inaccuracies in glucose sensing, inter- and intra-patient variability, and delays due to absorption of insulin from the subcutaneous tissue, all of which are being gradually addressed.
Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints
Authors: Snoeck Joke , Fellay Jacques , Bartha István , Douek Daniel C , Telenti Amalio
Published: December 2011

Background

The HIV-1 genome is subject to pressures that target the virus resulting in escape and adaptation. On the other hand, there is a requirement for sequence conservation because of functional and structural constraints. Mapping the sites of selective pressure and conservation on the viral genome generates a reference for understanding the limits to viral escape, and can serve as a template for the discovery of sites of genetic conflict with known or unknown host proteins.

Results

To build a thorough evolutionary, functional and structural map of the HIV-1 genome, complete subtype B sequences were obtained from the Los Alamos database. We mapped sites under positive selective pressure, amino acid conservation, protein and RNA structure, overlapping coding frames, CD8 T cell, CD4 T cell and antibody epitopes, and sites enriched in AG and AA dinucleotide motives. Globally, 33% of amino acid positions were found to be variable and 12% of the genome was under positive selection. Because interrelated constraining and diversifying forces shape the viral genome, we included the variables from both classes of pressure in a multivariate model to predict conservation or positive selection: structured RNA and α-helix domains independently predicted conservation while CD4 T cell and antibody epitopes were associated with positive selection.

Conclusions

The global map of the viral genome contains positive selected sites that are not in canonical CD8 T cell, CD4 T cell or antibody epitopes; thus, it identifies a class of residues that may be targeted by other host selective pressures. Overall, RNA structure represents the strongest determinant of HIV-1 conservation. These data can inform the combined analysis of host and viral genetic information.
Antidiabetic activity of isoquercetin in diabetic KK -Ay mice
Authors: Zhang Rui , Yao Yang , Wang Yingping , Ren Guixing
Published: December 2011

Background

Tartary buckwheat bran is an important natural source of quercetin and isoquercetin. Quercetin and isoquercetin are both powerful α-glucosidase inhibitors. Although the IC50 of isoquercetin as α-glucosidase inhibitor was much higher than that of quercetin, the bioavailability of isoquercetin was higher than that of quercetin. Hence, we are interested in the antidiabetic effect of isoquercetin in diabetic KK -Ay mice.

Methods

The hypoglycemic effect of isoquercetin in a type 2 diabetic animal model (KK-Ay mice) was studied. Isoquercetin was administrated at doses of 50, 100 and 200 mg/kg for 35 days.

Results

It was found that fasting blood glucose concentration was decreased with the 200 mg/kg group (p < 0.01) the most efficient compared with the diabetic control group. In addition, there was significant decrease in plasma C-peptide, triglyceride, total cholesterol and blood urea nitrogen levels after 35 days. Meanwhile, glucose tolerance was improved, and the immunoreactive of pancreatic islets β-cells was promoted.

Conclusions

These results suggest that isoquercetin had a regulative role in blood glucose level and lipids, and improved the function of pancreatic islets. Isoquercetin may be useful in the treatment of type 2 diabetes mellitus.
Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems
Authors: McDermott Jason E , Shankaran Harish , Eisfeld Amie J , Belisle Sarah E , Neuman Gabriele , Li Chengjun , McWeeney Shannon , Sabourin Carol , Kawaoka Yoshihiro , Katze Michael G , Waters Katrina M
Published: December 2011

Background

Understanding host response to influenza virus infection will facilitate development of better diagnoses and therapeutic interventions. Several different experimental models have been used as a proxy for human infection, including cell cultures derived from human cells, mice, and non-human primates. Each of these systems has been studied extensively in isolation, but little effort has been directed toward systematically characterizing the conservation of host response on a global level beyond known immune signaling cascades.

Results

In the present study, we employed a multivariate modeling approach to characterize and compare the transcriptional regulatory networks between these three model systems after infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Using this approach we identified functions and pathways that display similar behavior and/or regulation including the well-studied impact on the interferon response and the inflammasome. Our results also suggest a primary response role for airway epithelial cells in initiating hypercytokinemia, which is thought to contribute to the pathogenesis of H5N1 viruses. We further demonstrate that we can use a transcriptional regulatory model from the human cell culture data to make highly accurate predictions about the behavior of important components of the innate immune system in tissues from whole organisms.

Conclusions

This is the first demonstration of a global regulatory network modeling conserved host response between in vitro and in vivo models.
Recommendations for avoiding knee pain after intramedullary nailing of tibial shaft fractures
Authors: Labronici Pedro José , Santos Pires Robinson Esteves , Franco José Sérgio , Alvachian Fernandes Hélio Jorge , dos Reis Fernando Baldy
Published: December 2011

Background

The objective of this study is to analyze the proximal tibiofibular joint in patients with knee pain after treatment of tibial shaft fractures with locked intramedullary nail.

Findings

The proximal tibiofibular joint was analyzed in 30 patients, who reported knee pain after tibial nailing, and standard radiograph and computed tomography were performed to examine the proximal third of the tibia. Twenty patients (68.9%) presented the proximal screw crossing the proximal tibiofibular joint and 13 (44.8%) had already removed the nail and/or screw. Four patients (13.7%) reported complaint of knee pain. However, the screw did not reach the proximal tibiofibular joint. Five patients (17.2%) complained of knee pain although the screw toward the joint did not affect the proximal tibiofibular joint.

Conclusion

When using nails with oblique proximal lock, surgeons should be careful not to cause injury in the proximal tibiofibular joint, what may be one of the causes of knee pain. Thus, the authors suggest postoperative evaluation performing computed tomography when there is complaint of pain.
Identification of DNA methylation changes associated with human gastric cancer
Authors: Park Jung-Hoon , Park Jinah , Choi Jung Kyoon , Lyu Jaemyun , Bae Min-Gyun , Lee Young-Gun , Bae Jae-Bum , Park Dong Yoon , Yang Han-Kwang , Kim Tae-You , Kim Young-Joon
Published: December 2011

Background

Epigenetic alteration of gene expression is a common event in human cancer. DNA methylation is a well-known epigenetic process, but verifying the exact nature of epigenetic changes associated with cancer remains difficult.

Methods

We profiled the methylome of human gastric cancer tissue at 50-bp resolution using a methylated DNA enrichment technique (methylated CpG island recovery assay) in combination with a genome analyzer and a new normalization algorithm.

Results

We were able to gain a comprehensive view of promoters with various CpG densities, including CpG Islands (CGIs), transcript bodies, and various repeat classes. We found that gastric cancer was associated with hypermethylation of 5' CGIs and the 5'-end of coding exons as well as hypomethylation of repeat elements, such as short interspersed nuclear elements and the composite element SVA. Hypermethylation of 5' CGIs was significantly correlated with downregulation of associated genes, such as those in the HOX and histone gene families. We also discovered long-range epigenetic silencing (LRES) regions in gastric cancer tissue and identified several hypermethylated genes (MDM2, DYRK2, and LYZ) within these regions. The methylation status of CGIs and gene annotation elements in metastatic lymph nodes was intermediate between normal and cancerous tissue, indicating that methylation of specific genes is gradually increased in cancerous tissue.

Conclusions

Our findings will provide valuable data for future analysis of CpG methylation patterns, useful markers for the diagnosis of stomach cancer, as well as a new analysis method for clinical epigenomics investigations.
DNA vaccination with a gene encoding Toxoplasma gondii GRA6 induces partial protection against toxoplasmosis in BALB/c mice
Authors: Sun Xi-Meng , Zou Jun , AA Elashram Saeed , Yan Wen-Chao , Liu Xian-Yong , Suo Xun , Wang Heng , Chen Qi-Jun
Published: December 2011

Background

Infection with the protozoanToxoplasma gondiicauses serious public health problems and is of great economic importance worldwide. Protection from acute toxoplasmosis is known to be mediated by CD8+ T cells, but theT. gondiiantigens and host genes required for eliciting protective immunity have been poorly defined. TheT. gondiidense granule protein 6 (GRA6), recently proved to be highly immunogenic and produces fully immune protection inT. gondiiinfected BALB/c mice with an H-2Ldgene. The CD8+ T cell response of H-2Ldmice infected by theT. gondiistrain seemed to target entirely to a single GRA6 peptide HF10-H-2Ldcomplex.

Results

To determine whether a GRA6-based DNA vaccine can elicit protective immune responses toT. gondiiin BALB/c mice, we constructed a eukaryotic expression vector pcDNA3.1-HisGRA6 and tested its immunogenicity in a mouse model. BALB/c mice were vaccinated intramuscularly with three doses of GRA6 DNA and then challenged with a lethal dose ofT. gondiiRH strain tachyzoites. All immunized mice developed high levels of serum anti-GRA6 IgG antibodies, andin vitrosplenocyte proliferation was strongly enhanced in mice adjuvanted with levamisole (LMS). Immunization with pcDNA3.1-HisGRA6 with LMS resulted in 53.3% survival of challenged BALB/c mice as compared to 40% survival of BALB/c without LMS. Additionally, immunized Kunming mice without an allele of H-2Ldfailed to survive.

Conclusions

Our result supports the concept that the acquired immune response is MHC restricted. This study has a major implication for vaccine designs using a single antigen in a population with diverse MHC class I alleles.
Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation
Authors: Mirbolooki M Reza , Constantinescu Cristian C , Pan Min-Liang , Mukherjee Jogeshwar
Published: December 2011

Background

Brown adipose tissue [BAT] metabolism in vivo is vital for the development of novel strategies in combating obesity and diabetes. Currently, BAT is activated at low temperatures and measured using 2-deoxy-2-18F-fluoro-D-glucose [18F-FDG] positron-emission tomography [PET]. We report the use of β3-adrenergic receptor-mediated activation of BAT at ambient temperatures using (R, R)-5-[2-[2,3-(3-chlorphenyl)-2-hydroxyethyl-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate, disodium salt [CL316,243] (a selective β3-adrenoceptor agonist) and measured by 18F-FDG PET/computed tomography [CT].

Methods

Control and CL316,243-treated (2 mg/kg) male Sprague-Dawley rats were administered with 18F-FDG for PET/CT studies and were compared to animals at cold temperatures. Receptor-blocking experiments were carried out using propranolol (5 mg/kg). Dose effects of CL316,243 were studied by injecting 0.1 to 1 mg/kg 30 min prior to 18F-FDG administration. Imaging results were confirmed by autoradiography, and histology was done to confirm BAT activation.

Results

CL316,243-activated interscapular BAT [IBAT], cervical, periaortic, and intercostal BATs were clearly visualized by PET. 18F-FDG uptake of IBAT was increased 12-fold by CL316,243 vs. 1.1-fold by cold exposure when compared to controls. 18F-FDG uptake of the CL-activated IBAT was reduced by 96.0% using intraperitoneal administration of propranolol. Average 18F-FDG uptake of IBAT increased 3.6-, 3.5-, and 7.6-fold by doses of 0.1, 0.5, and 1 mg/kg CL, respectively. Ex vivo
18F-FDG autoradiography and histology of transverse sections of IBAT confirmed intense uptake in the CL-activated group and activated IBAT visualized by PET.

Conclusion

Our study indicated that BAT metabolic activity could be evaluated by 18F-FDG PET using CL316,243 at ambient temperature in the rodent model. This provides a feasible and reliable method to study BAT metabolism.
Regulatory mechanisms for the production of BAFF and IL-6 are impaired in monocytes of patients of primary Sjögren's syndrome
Authors: Yoshimoto Keiko , Tanaka Maiko , Kojima Masako , Setoyama Yumiko , Kameda Hideto , Suzuki Katsuya , Tsuzaka Kensei , Ogawa Yoko , Tsubota Kazuo , Abe Tohru , Takeuchi Tsutomu
Published: December 2011

Introduction

In this study, we investigated possible aberrations of monocytes from patients with primary Sjögren's syndrome (pSS). We focused on B-cell-activating factor of the TNF family (BAFF) and IL-6 because they are both produced by monocytes and are known to be involved in the pathogenesis of pSS.

Methods

Peripheral monocytes were prepared from both pSS patients and normal individuals. The cells were stimulated in vitro with IFN-γ, and the amounts of IL-6 and soluble BAFF (sBAFF) produced by the cells were quantitated. The effect of sBAFF itself on the production of IL-6 was also studied. To investigate the response of pSS monocytes to these stimuli, the expression levels of the genes encoding BAFF receptors and IL-6-regulating transcription factors were quantitated.

Results

Peripheral pSS monocytes produced significantly higher amounts of sBAFF and IL-6 than normal monocytes did, even in the absence of stimulation. The production of these cytokines was significantly increased upon stimulation with IFN-γ. The elevated production of IL-6 was significantly suppressed by an anti-BAFF antibody. In addition, stimulation of pSS monocytes with sBAFF induced a significant increase in IL-6 production. Moreover, the expression levels of a BAFF receptor and transcription factors regulating IL-6 were significantly elevated in pSS monocytes compared to normal monocytes.

Conclusions

The results of the present study suggest that the mechanisms underlying the production of sBAFF and IL-6 are impaired in pSS monocytes. Our research implies that this impairment is due to abnormally overexpressed IL-6-regulating transcription factors and a BAFF receptor. These abnormalities may cause the development of pSS.