bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of combination therapy of allicin and fenofibrate on high fat diet-induced vascular endothelium dysfunction and liver damage in rats
Authors: Li Weihong , Wang Daxin , Song Guohua , Zuo Chunxia , Qiao Xianfu , Qin Shucun
Published: May 2012

Background

It is designed to investigate the effects of combination therapy of allicin and fenofibrate on the endothelial and liver functions in rats with hyperlipidemia.

Methods

The healthy male Wistar rats fed high fat diet were treated with fenofibrate (80 mg/kg per day) alone, allicin (60 mg/kg per day) alone and a lower dasage of combined therapy (allicin 20 mg/kg per day and fenofibrate 30 mg/kg per day) respectively for 8 weeks. The serum levels of cholesterol, triglyceride, nitrogen oxidative, alanine transferase (ALT) and aspartate transferase (AST) were determined. Acetylcholine-induced endothelium-dependent vascular relaxation (EDVR) of aorta rings was tested, and the morphologic changes of liver tissue were observed.

Results

Compared with high fat diet control, fenofibrate alone or the combined therapy increased remarkably the levels of high density lipoprotein respectively (P < 0.05). Both single and combined therapy of fenofibrate and allicin significantly enhanced the levels of NO (P < 0.01 or P < 0.05), but the combined therapy had greatest high EDVR responses (P < 0.01). Furthermore, the reduced levels of ALT and AST were significantly obvious in the combined therapy groups (P < 0.01 or P < 0.05). In addition, the lower dosage of combined therapy significantly ameliorated severe fatty degeneration of liver cells occurred in the high fat diet fed rat although the single fenofibrate treatment showed spotty necrosis of liver cells and bile duct expansion.

Conclusion

Combination therapy with allicin and fenofibrate can effectively enhance the protective effects on endothelial function and reduce the hepatic damage in rats with hyperlipidemia.
Polymorphism of rs1044925 in the acyl-CoA:cholesterol acyltransferase-1 gene and serum lipid levels in the Guangxi Bai Ku Yao and Han populations
Authors: Wu Dong-Feng , Yin Rui-Xing , Aung Lynn Htet Htet , Hu Xi-Jiang , Cao Xiao-Li , Miao Lin , Li Qing , Yan Ting-Ting , Wu Jin-Zhen , Pan Shang-Ling
Published: May 2012

Background

The association of rs1044925 polymorphism in the acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) gene and serum lipid profiles is not well known in different ethnic groups. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was carried out to clarify the association of rs1044925 polymorphism in the ACAT-1 gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations.

Methods

A total of 626 subjects of Bai Ku Yao and 624 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of rs1044925 polymorphism in the ACAT-1 gene was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.

Results

The levels of serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of A and C alleles was 79.0% and 21.0% in Bai Ku Yao, and 87.3% and 12.7% in Han (P < 0.001); respectively. The frequency of AA, AC and CC genotypes was 63.2%, 31.4% and 5.2% in Bai Ku Yao, and 75.6%, 23.2% and 1.1% in Han (P < 0.001); respectively. The levels of TC, LDL-C and ApoB in Bai Ku Yao but not in Han were different between the AA and AC/CC genotypes in females but not in males (P < 0.05 for all). The C allele carriers had lower serum TC, LDL-C and ApoB levels as compared with the C allele noncarriers. The levels of TC, LDL-C and ApoB in Bai Ku Yao but not in Han were correlated with genotypes in females but not in males (P < 0.05 for all). Serum lipid parameters were also correlated with sex, age, body mass index, alcohol consumption, and blood pressure in both ethnic groups (P < 0.05-0.001).

Conclusions

These results suggest that the polymorphism of rs1044925 in the ACAT-1 gene is mainly associated with female serum TC, LDL-C and ApoB levels in the Bai Ku Yao population. The C allele carriers had lower serum TC, LDL-C and ApoB levels than the C allele noncarriers.
Curcumin inhibits cholesterol uptake in Caco-2 cells by down-regulation of NPC1L1 expression
Authors: Feng Dan , Ohlsson Lena , Duan Rui-Dong
Published: May 2012

Background

Curcumin is a polyphenol and the one of the principle curcuminoids of the spice turmeric. Its antioxidant, anti-cancer and anti-inflammatory effects have been intensively studied. Previous in vivo studies showed that administration of curcumin also decreased cholesterol levels in the blood, and the effects were considered to be related to upregulation of LDL receptor. However, since plasma cholesterol levels are also influenced by the uptake of cholesterol in the gut, which is mediated by a specific transporter Niemann-Pick Cl-like 1 (NPC1L1) protein, the present study is to investigate whether curcumin affects cholesterol uptake in the intestinal Caco-2 cells.

Methods

Caco-2 cells were cultured to confluence. The micelles composed of bile salt, monoolein, and 14C-cholesterol were prepared. We first incubated the cells with the micelles in the presence and absence of ezetimibe, the specific inhibitor of NPC1L1, to see whether the uptake of the cholesterol in the cells was mediated by NPC1L1. We then pretreated the cells with curcumin at different concentrations for 24 h followed by examination of the changes of cholesterol uptake in these curcumin-treated cells. Finally we determined whether curcumin affects the expression of NPC1L1 by both Western blot analysis and qPCR quantification.

Results

We found that the uptake of radioactive cholesterol in Caco-2 cells was inhibited by ezetimibe in a dose-dependent manner. The results indicate that the uptake of cholesterol in this study was mediated by NPC1L1. We then pretreated the cells with 25-100 μM curcumin for 24 h and found that such a treatment dose-dependently inhibited cholesterol uptake with 40% inhibition obtained by 100 μM curcumin. In addition, we found that the curcumin-induced inhibition of cholesterol uptake was associated with significant decrease in the levels of NPC1L1 protein and NPC1L1 mRNA, as analyzed by Western blot and qPCR, respectively.

Conclusion

Curcumin inhibits cholesterol uptake through suppression of NPC1L1 expression in the intestinal cells.
Proteome differences associated with fat accumulation in bovine subcutaneous adipose tissues
Authors: Zhao Yong Mei , Basu Urmila , Dodson Michael V , Basarb John A , Guan Le Luo
Published: May 2012

Background

The fat components of red meat products have been of interest to researchers due to the health aspects of excess fat consumption by humans. We hypothesized that differences in protein expression have an impact on adipose tissue formation during beef cattle development and growth. Therefore, in this study we evaluated the differences in the discernable proteome of subcutaneous adipose tissues of 35 beef crossbred steers [Charolais × Red Angus (CHAR) (n = 13) and Hereford × Angus (HEAN) (n = 22)] with different back fat (BF) thicknesses. The goal was to identify specific protein markers that could be associated with adipose tissue formation in beef cows.

Results

Approximately 541-580 protein spots were detected and compared in each crossbred group, and 33 and 36 protein spots showed expression differences between tissues with high and low BF thicknesses from HEAN and CHAR crossbed, respectively. The annexin 1 protein was highly expressed in both crossbred steers that had a higher BF thickness (p < 0.05) and this was further validated by a western blot analysis. In 13 tissues of CHAR animals and 22 tissues of HEAN animals, the relative expression of annexin 1 was significantly different (p < 0.05) between tissues with high and low BF thicknesses.

Conclusion

The increased expression of annexin 1 protein has been found to be associated with higher BF thickness in both crossbred steers. This result lays the foundation for future studies to develop the protein marker for assessing animals with different BF thickness.
A prospective, randomised, controlled clinical study on the assessment of tolerability and of clinical efficacy of Merional (hMG-IBSA) administered subcutaneously versus Merional administered intramuscularly in women undergoing multifollicular ovarian stimulation in an ART programme (IVF)
Authors: Alviggi Carlo , Revelli Alberto , Anserini Paola , Ranieri Antonio , Fedele Luigi , Strina Ida , Massobrio Marco , Ragni Nicola , De Placido Giuseppe
Published: May 2012

Background

Multifollicular ovarian stimulation (MOS) is widely used in IVF and the compliance to treatment is deeply influenced by the tolerability of the medication(s) used and by the ease of self-administration. This prospective, controlled, randomised, parallel group open label, multicenter, phase III, equivalence study has been aimed to compare the clinical effectiveness (in terms of oocytes obtained) and tolerability of subcutaneous (s.c.) self-administered versus classical intramuscular (i.m.) injections of Merional, a new highly-purified hMG preparation.

Methods

A total of 168 normogonadotropic women undergoing IVF were enrolled. Among them, 160 achieved pituitary suppression with a GnRH-agonist long protocol and were randomised to MOS treatment with Merional s.c. or i.m. They started MOS with a standard hMG dose between 150–300 IU, depending upon patient's age, and underwent a standard IVF procedure.

Results

No statistically significant difference in the mean number of collected oocytes (primary endpoint) was observed between the two study subgroups (7.46, SD 4.24 vs. 7.86, SD 4.28 in the s.c. and i.m. subgroups, respectively). As concerns the secondary outcomes, both the pregnancy and the clinical pregnancy rates were comparable between subgroups. The incidence of adverse events was similar in the two groups (2.4% vs. 3.7%, respectively). Pain at injection site was reported only the i.m. group (13.9% of patients).

Conclusion

Merional may be used by s.c. injections in IVF with an effectiveness in terms of retrieved oocytes that is equivalent to the one obtained with i.m administration and with a better local tolerability. With the limitations due to the sample size af this study, s.c. and i.m. administration routes seem to have the same overall safety.
Phosphorylation meets nuclear import: a review
Authors: Nardozzi Jonathan D , Lott Kaylen , Cingolani Gino
Published: May 2012

Phosphorylation is the most common and pleiotropic modification in biology, which plays a vital role in regulating and finely tuning a multitude of biological pathways. Transport across the nuclear envelope is also an essential cellular function and is intimately linked to many degeneration processes that lead to disease. It is therefore not surprising that phosphorylation of cargos trafficking between the cytoplasm and nucleus is emerging as an important step to regulate nuclear availability, which directly affects gene expression, cell growth and proliferation. However, the literature on phosphorylation of nucleocytoplasmic trafficking cargos is often confusing. Phosphorylation, and its mirror process dephosphorylation, has been shown to have opposite and often contradictory effects on the ability of cargos to be transported across the nuclear envelope. Without a clear connection between attachment of a phosphate moiety and biological response, it is difficult to fully understand and predict how phosphorylation regulates nucleocytoplasmic trafficking. In this review, we will recapitulate clue findings in the field and provide some general rules on how reversible phosphorylation can affect the nuclear-cytoplasmic localization of substrates. This is only now beginning to emerge as a key regulatory step in biology.
Place of birth, duration of residence, neighborhood immigrant composition and body mass index in New York City
Authors: Park Yoosun , Neckerman Kathryn M , Quinn James , Weiss Christopher , Rundle Andrew
Published: May 2012

Background

Past research has suggested that changes in culture explain the substantial weight gain seen in many immigrant groups with length of residence in the U.S. and across generations of residence in the U.S. However, it has been theorized that those settling in immigrant and co-ethnic neighborhoods may be buffered against this acculturative process and will be more likely to maintain home country dietary and physical activity patterns. To investigate this theory we incorporated measures of neighborhood immigrant composition into analyses of individual's body mass index (BMI) and generation of immigration and duration of residence in the U.S.

Methods

Multilevel analyses were performed using objectively measured height and weight and survey data on diet and physical activity from a sample of 13,011 residents of New York City. Census data were used to calculate the proportion of foreign-born residents and extent of household linguistic isolation in a ½ mile radial buffer around the subject's home.

Results

Foreign birth was associated with a significantly lower BMI (-1.09 BMI units, P < 0.001). This association was weakest among Asians (-0.66 BMI units, P = 0.08) and strongest among Black-Caribbeans (-1.41 BMI units, P = 0.07). After controlling for individual level variables, neighborhood proportion foreign-born was not associated with BMI, but increasing neighborhood linguistic isolation was inversely associated with BMI among Hispanics (-2.97 BMI units, P = 0.03). Furthermore among Hispanics, the association between foreign birth and BMI was stronger in low linguistic isolation neighborhoods (-1.36 BMI units, P < 0.0001) as compared to in high linguistic isolation levels (-0.42 BMI units, P = 0.79). Increasing duration of residence in the U.S. was significantly associated with higher BMI overall and among Hispanics.

Conclusion

The analyses suggest that acculturation is associated with weight gain, and that neighborhood characteristics are only associated with BMI among Hispanics. However, we suggest that changes in body size currently interpreted as post-migration effects of acculturation to U.S. norms may in fact reflect changes in norms that are taking place internationally.
CD20-negative de novo diffuse large B-cell lymphoma in HIV-negative patients: A matched case-control analysis in a single institution
Authors: Li Ya-Jun , Li Zhi-Ming , Rao Hui-Lan , Xia Yi , Huang Hui-Qiang , Xia Zhong-Jun , Li Su , Li Wen-Yu , Jiang Wen-Qi
Published: May 2012

Background

HIV-negative, CD20-negative de novo diffuse large B-cell lymphoma (DLBCL) patients has rarely been reported. To elucidate the nature of this entity, we retrospectively reviewed the data of 1,456 consecutive de novo DLBCL patients who were treated at Sun Yat-Sen University Cancer Center between January 1999 and March 2011.

Methods

The pathologic characteristics of CD20-negative patients, clinical features, response to initial treatment, and outcomes of 28 patients with available clinical data (n = 21) were reviewed. Then, a matched case-control (1:3) analysis was performed to compare patients with CD20-negative and -positive DLBCL.

Results

The median age of the 28 CD20-negative DLBCL patients was 48 years, with a male-female ratio of 20:8. Seventeen of 22 (77.3%) CD20-negative DLBCL cases were of the non-germinal centre B-cell (non-GCB) subtype. High Ki67 expression (≥80%), an index of cell proliferation, was demonstrated in 17 of 24 (70.8%) cases. Extranodal involvement (≥ 1 site) was observed in 76.2% of the patients. Following initial therapy, 9 of 21 (42.9%) cases achieved complete remission, 4 (19%) achieved partial remission, 1 (4.8%) had stable disease, and 7 (33.3%) had disease progression. The median overall survival was 23 months. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 30.5% and 35%, respectively. A matched case-control analysis showed that patients with CD20-negative and -positive DLBCL did not exhibit a statistically significant difference with respect to the main clinical characteristics (except extranodal involvement), whereas the patients with CD20-positive DLBCL had a better survival outcome with 3-year PFS (P = 0.008) and OS (P = 0.008) rates of 52% and 74.1%, respectively.

Conclusions

This study suggests that HIV-negative, CD20-negative de novo DLBCL patients have a higher proportion of non-GCB subtype, a higher proliferation index, more frequent extranodal involvement, a poorer response, and a poorer prognosis to conventional treatment compared to patients with CD20-positive DLBCL. Further studies are warranted to investigate new target and optimal therapy of CD20-negative de novo DLBCL.
Human tracking with an infrared camera using a curve matching framework
Authors: Lee Suk Jin , Shah Gaurav , Bhattacharya Arka Aloke , Motai Yuichi
Published: May 2012

The Kalman filter (KF) has been improved for a mobile robot to human tracking. The proposed algorithm combines a curve matching framework and KF to enhance prediction accuracy of target tracking. Compared to other methods using normal KF, the Curve Matched Kalman Filter (CMKF) method predicts the next movement of the human by taking into account not only his present motion characteristics, but also the previous history of target behavior patterns-the CMKF provides an algorithm that acquires the motion characteristics of a particular human and provides a computationally inexpensive framework of human-tracking system. The proposed method demonstrates an improved target tracking using a heuristic weighted mean of two methods, i.e., the curve matching framework and KF prediction. We have conducted the experimental test in an indoor environment using an infrared camera mounted on a mobile robot. Experimental results validate that the proposed CMKF increases prediction accuracy by more than 30% compared to normal KF when the characteristic patterns of target motion are repeated in the target trajectory.
Eukaryotic protein production in designed storage organelles
Authors: Torrent Margarita , Llompart Blanca , Lasserre-Ramassamy Sabine , Llop-Tous Immaculada , Bastida Miriam , Marzabal Pau , Westerholm-Parvinen Ann , Saloheimo Markku , Heifetz Peter B , Ludevid M Dolors
Published: May 2012

Background

Protein bodies (PBs) are natural endoplasmic reticulum (ER) or vacuole plant-derived organelles that stably accumulate large amounts of storage proteins in seeds. The proline-rich N-terminal domain derived from the maize storage protein γ zein (Zera) is sufficient to induce PBs in non-seed tissues of Arabidopsis and tobacco. This Zera property opens up new routes for high-level accumulation of recombinant proteins by fusion of Zera with proteins of interest. In this work we extend the advantageous properties of plant seed PBs to recombinant protein production in useful non-plant eukaryotic hosts including cultured fungal, mammalian and insect cells.

Results

Various Zera fusions with fluorescent and therapeutic proteins accumulate in induced PB-like organelles in all eukaryotic systems tested: tobacco leaves, Trichoderma reesei, several mammalian cultured cells and Sf9 insect cells. This accumulation in membranous organelles insulates both recombinant protein and host from undesirable activities of either. Recombinant protein encapsulation in these PBs facilitates stable accumulation of proteins in a protected sub-cellular compartment which results in an enhancement of protein production without affecting the viability and development of stably transformed hosts. The induced PBs also retain the high-density properties of native seed PBs which facilitate the recovery and purification of the recombinant proteins they contain.

Conclusion

The Zera sequence provides an efficient and universal means to produce recombinant proteins by accumulation in ER-derived organelles. The remarkable cross-kingdom conservation of PB formation and their biophysical properties should have broad application in the manufacture of non-secreted recombinant proteins and suggests the existence of universal ER pathways for protein insulation.
Analysis of cell identity, morphology, apoptosis and mitotic activity in a primary neural cell culture system in Drosophila
Authors: Moraru Manuela M , Egger Boris , Bao Diarra B , Sprecher Simon G
Published: May 2012

In Drosophila, most neurogenetic research is carried out in vivo. Mammalian research demonstrates that primary cell culture techniques provide a powerful model to address cell autonomous and non-autonomous processes outside their endogenous environment. We developed a cell culture system in Drosophila using wildtype and genetically manipulated primary neural tissue for long-term observations. We assessed the molecular identity of distinct neural cell types by immunolabeling and genetically expressed fluorescent cell markers. We monitored mitotic activity of cell cultures derived from wildtype and tumorous larval brains. Our system provides a powerful approach to unveil developmental processes in the nervous system and to complement studies in vivo.
Fbxw7 regulates Notch to control specification of neural precursors for oligodendrocyte fate
Authors: Snyder Julia L , Kearns Christina A , Appel Bruce
Published: May 2012

Background

In the developing vertebrate nervous system elevated levels of Notch signaling activity can block neurogenesis and promote formation of glial cells. The mechanisms that limit Notch activity to balance formation of neurons and glia from neural precursors are poorly understood.

Results

By screening for mutations that disrupt oligodendrocyte development in zebrafish we found one allele, called vu56, that produced excess oligodendrocyte progenitor cells (OPCs). Positional cloning revealed that the vu56 allele is a mutation of fbxw7, which encodes the substrate recognition component of a ubiquitin ligase that targets Notch and other proteins for degradation. To investigate the basis of the mutant phenotype we performed in vivo, time-lapse imaging, which revealed that the increase in OPC number resulted from production of extra OPCs by ventral spinal cord precursors and not from changes in OPC proliferation or death. Notch signaling activity was elevated in spinal cord precursors of fbxw7 mutant zebrafish and inhibition of Notch signaling suppressed formation of excess OPCs.

Conclusion

Notch signaling promotes glia cell formation from neural precursors in vertebrate embryos. Our data indicate that Fbxw7 helps attenuate Notch signaling during zebrafish neural development thereby limiting the number of OPCs.
Milk progesterone enzyme-linked immunosorbent assay as a tool to investigate ovarian cyclicity of water buffaloes in relation to body condition score and milk production
Authors: Banu Turgish A , Shamsuddin Mohammed , Bhattacharjee Jayonta , Islam Mohammad F , Khan Saiful I , Ahmed Jalal U
Published: May 2012

Background

Application of assisted reproductive technologies in buffaloes is limited to some extent by farmers’ inability to detect oestrus because of its poor expression. The present study aimed at investigating reliability of a milk progesterone enzyme-linked immunosorbent assay (ELISA) to assess the ovarian cyclicity during post partum, oestrus and post-breeding periods in water buffaloes.

Methods

Progesterone concentrations were measured by an ELISA in milk of 23 postpartum buffaloes in relation to oestrus, pregnancy, body condition score (BCS) and milk production. Two milk samples were taken at 10 days intervals, every month starting from day 30 and continued to day 150 post partum. BCS and milk production were recorded during sample collection. Milk samples from bred buffaloes were collected at Day 0 (day of breeding), Days 10–12 and Days 22–24. Defatted milk was preserved at −80°C until analysis. Pregnancy was confirmed by palpation per rectum on Days 70–90.

Results

Seventeen buffaloes had 47 ovulatory cycles, one to four in each, 13 were detected in oestrus once (28 % oestrus detection rate). Progesterone concentration ≥1 ng/ml in one of the two 10-day-interval milk samples reflected ovulation and corpus luteum formation. The intervals between calving to first luteal activity and to first detected oestrus varied from 41 to 123 days (n = 17) and 83 to 135 (n = 13) days, respectively. Eight buffaloes were bred in the course of the study and seven were found pregnant. These buffaloes had a progesterone profile of low (<1 ng/ml), high (≥ 1 ng/ml) and high (≥ 1 ng/ml) on Day 0, Days 10–12 and Days 22–24, respectively. Buffaloes cycling later in the postpartum period had fewer missed oestruses (P < 0.05). Buffaloes with a superior BCS had a shorter calving to oestrus interval and produced more milk (P < 0.05).

Conclusions

Milk progesterone ELISA is a reliable tool for monitoring ovarian cyclicity and good BCS may be an indicator of resuming cyclicity in water buffalo.
Robustness from flexibility in the fungal circadian clock
Authors: Akman Ozgur E , Rand David A , Brown Paul E , Millar Andrew J
Published: May 2012

Background

Robustness is a central property of living systems, enabling function to be maintained against environmental perturbations. A key challenge is to identify the structures in biological circuits that confer system-level properties such as robustness. Circadian clocks allow organisms to adapt to the predictable changes of the 24-hour day/night cycle by generating endogenous rhythms that can be entrained to the external cycle. In all organisms, the clock circuits typically comprise multiple interlocked feedback loops controlling the rhythmic expression of key genes. Previously, we showed that such architectures increase the flexibility of the clock's rhythmic behaviour. We now test the relationship between flexibility and robustness, using a mathematical model of the circuit controlling conidiation in the fungus Neurospora crassa.

Results

The circuit modelled in this work consists of a central negative feedback loop, in which the frequency (frq) gene inhibits its transcriptional activator white collar-1 (wc-1), interlocked with a positive feedback loop in which FRQ protein upregulates WC-1 production. Importantly, our model reproduces the observed entrainment of this circuit under light/dark cycles with varying photoperiod and cycle duration. Our simulations show that whilst the level of frq mRNA is driven directly by the light input, the falling phase of FRQ protein, a molecular correlate of conidiation, maintains a constant phase that is uncoupled from the times of dawn and dusk. The model predicts the behaviour of mutants that uncouple WC-1 production from FRQ's positive feedback, and shows that the positive loop enhances the buffering of conidiation phase against seasonal photoperiod changes. This property is quantified using Kitano's measure for the overall robustness of a regulated system output. Further analysis demonstrates that this functional robustness is a consequence of the greater evolutionary flexibility conferred on the circuit by the interlocking loop structure.

Conclusions

Our model shows that the behaviour of the fungal clock in light-dark cycles can be accounted for by a transcription-translation feedback model of the central FRQ-WC oscillator. More generally, we provide an example of a biological circuit in which greater flexibility yields improved robustness, while also introducing novel sensitivity analysis techniques applicable to a broader range of cellular oscillators.
Stress-specific response of the p53-Mdm2 feedback loop
Authors: Hunziker Alexander , Jensen Mogens H , Krishna Sandeep
Published: May 2012

Background

The p53 signalling pathway has hundreds of inputs and outputs. It can trigger cellular senescence, cell-cycle arrest and apoptosis in response to diverse stress conditions, including DNA damage, hypoxia and nutrient deprivation. Signals from all these inputs are channeled through a single node, the transcription factor p53. Yet, the pathway is flexible enough to produce different downstream gene expression patterns in response to different stresses.

Results

We construct a mathematical model of the negative feedback loop involving p53 and its inhibitor, Mdm2, at the core of this pathway, and use it to examine the effect of different stresses that trigger p53. In response to DNA damage, hypoxia, etc., the model exhibits a wide variety of specific output behaviour - steady states with low or high levels of p53 and Mdm2, as well as spiky oscillations with low or high average p53 levels.

Conclusions

We show that even a simple negative feedback loop is capable of exhibiting the kind of flexible stress-specific response observed in the p53 system. Further, our model provides a framework for predicting the differences in p53 response to different stresses and single nucleotide polymorphisms.
Molecular cytogenetic characterization of undifferentiated embryonal sarcoma of the liver: a case report and literature review
Authors: Hu Xiaoxia , Chen Haiying , Jin Meishan , Wang Xianfu , Lee Jiyun , Xu Weihong , Zhang Rui , Li Shibo , Niu Junqi
Published: May 2012

Undifferentiated embryonal sarcoma of the liver (UESL) represents a heterogeneous group of tumors derived from mesenchymal tissues. Earlier cytogenetic studies in limited cases demonstrated that UESL is associated with a recurrent translocation t(11;19)(q11;q13.3-q13.4) or add(19)(q13.4). In this report, we present our array comparative genomic hybridization (aCGH), fluorescencein situhybridization (FISH) findings, and a missense mutation ofTP53gene by DNA sequencing in a 19-year-old patient with UESL. The data were compared to laboratory findings reported by previous studies.
The prognostic value of left ventricular systolic function measured by tissue Doppler imaging in septic shock
Authors: Weng Li , Liu Yong-tai , Du Bin , Zhou Jian-fang , Guo Xiao-xiao , Peng Jin-min , Hu Xiao-yun , Zhang Shu-yang , Fang Quan , Zhu Wen-ling
Published: May 2012

Introduction

Left ventricular (LV) dysfunction is common in septic shock. Its association with the clinical outcome is still controversial. Tissue Doppler imaging (TDI) is a useful tool to quantify LV function; however, little knowledge is available about the prognostic value of these TDI variables in septic shock. Therefore, we performed this prospective study to determine the role of TDI variables in septic shock.

Methods

Patients with septic shock in a medical intensive care unit were studied with transthoracic echocardiography with TDI within 24 hours after the onset of septic shock. Baseline clinical, laboratory, and echocardiographic variables were prospectively collected. Independent predictors of 90-day mortality were analyzed with the Cox regression model.

Results

During a 20-month period, 61 patients were enrolled in the study. The 90-day mortality rate was 39%; the mean APACHE IV score was 84 (68 to 97). Compared with survivors, nonsurvivors exhibited significantly higher peak systolic velocity measured at the mitral annulus (Sa) (11.0 (9.1 to 12.5) versus 7.8 (5.5 to 9.0) cm/sec; P < 0.0001), lower PaO2/FiO2 (123 (83 to 187) versus 186 (142 to 269) mm Hg; P = 0.002], higher heart rate (120 (90 to 140) versus 103 (90 to 114) beats/min; P = 0.004], and ahigher dose of norepinephrine (0.6 (0.2 to 1.0) versus 0.3 (0.2 to 0.5) μg/kg/min; P = 0.007]. In the multivariate analysis, Sa > 9 cm/sec (hazard ratio (HR), 5.559; 95% confidence interval (CI), 2.160 to 14.305; P < 0.0001), dose of norepinephrine (HR, 1.964; 95% CI, 1.338 to 2.883; P = 0.001), and PaO2/FiO2 (HR, 0.992; 95% CI, 0.984 to 0.999; P = 0.031) remain independent predictors of 90-day mortality in septic-shock patients.

Conclusions

Our study demonstrated that LV systolic function as determined by TDI, in particular, Sa, might be associated with mortality in patients with septic shock.
Binding of Dynein Intermediate Chain 2 to Paxillin controls Focal adhesion dynamics and migration.
Authors: Rosse Carine , Boeckeler Katrina , Linch Mark , Radtke Simone , Frith David , Barnouin Karin , Morsi Ali Sayed , Hafezparast Majid , Howell Michael , Parker Peter J.
Published: May 2012

In migrating NRK cells, aPKCs control the dynamics of turnover of paxillin-containing focal adhesions (FA) determining migration rate. Using a proteomic approach (2-DIGE), dynein intermediate chain 2 (dyneinIC2) was identified as a protein phosphorylated inducibly during cell migration in a PKC regulated manner. By gene silencing and co-immunoprecipitation studies, we show that dyneinIC2 regulates the speed of cell migration dependent on its interaction with paxillin. This interaction is controlled by Serine 84 phosphorylation, which lies on the aPKC pathway. The evidence presented thus links aPKC control of migration to the dynein control of FA turnover through paxillin.
Splice-variants of the P2X7 receptor reveal differential agonist-dependence and functional coupling with pannexin-1
Authors: Xu Xing Jian , Boumechache Miyyada , Robinson Lucy E. , Marschall Viola , Gorecki Dariusz C. , Masin Marianela , Murrell-Lagnado Ruth
Published: May 2012

P2X7 receptors function as ATP-gated cation channels but also interact with other proteins as part of a larger signalling complex to mediate a variety of downstream responses dependent upon the cell type in which they are expressed. Receptor mediated membrane permeabilization to large molecules precedes the induction of cell death but remains poorly understood and the mechanisms that underlie differential sensitivity to NAD are also unknown. By studying alternative variants of the mouse P2X7 receptor we show that sensitivity to NAD is mediated via the P2X7k variant which has a much more restricted distribution than the P2X7a receptor, but is expressed in T-lymphocytes. The altered N-terminus and TM1 of the P2X7k receptor enhances the stability of the active state of this variant compared to P2X7a thereby increasing the efficacy of NAD-dependent ADP-ribosylation as measured by ethidium uptake, a rise in intracellular Ca2+ and the activation of inward currents. Coexpression of P2X7k and P2X7a receptors reduced NAD-sensitivity. P2X7k receptor-mediated ethidium uptake was also triggered by much lower BzATP concentrations and was insensitive to the P451L single nucleotide polymorphism. P2X7k receptor mediated ethidium uptake occurred independently of pannexin-1 suggesting a pathway intrinsic to the receptor. Only for the P2X7aL451 receptor could we resolve a component of dye-uptake dependent upon pannexin-1. Signalling occurred downstream of the activation of caspases rather than involving direct cross talk between the channels. An in-situ proximity assay showed, however, close association between P2X7 receptors and pannexin-1, which would facilitate ATP efflux through pannexin-1 acting in an autocrine manner.
CKIP-1 REGULATES MAMMALIAN AND ZEBRAFISH MYOBLAST FUSION
Authors: Baas Dominique , Caussanel-Boude Sabine , Guiraud Alexandre , Calhabeu Frederico , Delaune-Henry Emilie , Pilot Fanny , Chopin Emilie , Machuca-Gayet Irma , Vernay Aurélia , Bertrand Stéphanie , Rual Jean-François , Jurdic Pierre , Hill David E. , Vidal Marc , Schaeffer Laurent , Goillot Evelyne
Published: May 2012

Multinucleated muscle fibres arise by fusion of precursor cells called myoblasts. We previously showed that CKIP-1 ectopic expression in C2C12 myoblasts increased cell fusion. In this work, we report that CKIP-1 depletion drastically impairs C2C12 myoblast fusion in vitro and in vivo during zebrafish muscle development. Within developing fast-twich myotome, Ckip-1 localizes at the periphery of fast precursor cells, closed to the plasma membrane. Unlike wild-type myoblasts that form spatially arrayed multinucleated fast myofibers, Ckip-1 deficient myoblasts show a drastic reduction in fusion capacity. Search for CKIP-1 binding partners identified ARPC1 subunit of Arp2/3 actin nucleation complex essential for myoblast fusion. We demonstrate that CKIP-1, through binding to plasma membrane phosphoinositides via its PH domain, regulates cell morphology and lamellipodia formation by recruiting the Arp2/3 complex at the plasma membrane. These results establish CKIP-1 as a regulator of cortical actin that recruits the Arp2/3 complex at the plasma membrane essential for muscle precursor elongation and fusion.
BRCA1-associated exclusion of 53BP1 from DNA damage sites underlies temporal control of DNA repair
Authors: Chapman J. Ross , Sossick Alex J. , Boulton Simon J. , Jackson Stephen P.
Published: May 2012

Following irradiation, numerous DNA-damage-responsive proteins rapidly redistribute into microscopically visible subnuclear aggregates, termed ionising-radiation-induced foci (IRIF). How the enrichment of proteins on damaged chromatin actually relates to DNA repair remains unclear. Here, we use super-resolution microscopy to examine the spatial distribution of BRCA1 and 53BP1 proteins within single IRIF at subdiffraction-limit resolution, yielding an unprecedented increase in detail that was not previously apparent by conventional microscopy. Consistent with a role for 53BP1 in promoting DNA double-strand break repair by non-homologous end joining, 53BP1 enrichment in IRIF is most prominent in the G0/G1 cell cycle phases, where it is enriched in dense globular structures. By contrast, as cells transition through S phase, the recruitment of BRCA1 into the core of IRIF is associated with an exclusion of 53BP1 to the focal periphery, leading to an overall reduction of 53BP1 occupancy at DNA damage sites. Our data suggest that the BRCA1-associated IRIF core corresponds to chromatin regions associated with repair by homologous recombination, and the enrichment of BRCA1 in IRIF represents a temporal switch in the DNA repair program. We propose that BRCA1 antagonises 53BP1-dependent DNA repair in S phase by inhibiting its interaction with chromatin proximal to damage sites. Furthermore, the genomic instability exhibited by BRCA1-deficient cells might result from a failure to efficiently exclude 53BP1 from such regions during S phase.
The impact of beta-blockers on mortality in stable angina: a meta-analysis
Authors: Huang H L , Fox K A A
Published: May 2012

Beta-blockers are recommended as first-line symptomatic treatment for stable angina. However, their impact on mortality outside the context of myocardial infarction is unknown. We performed a meta-analysis of all randomized trials of beta-blockers in stable angina. Medical databases and cardiology journals were searched for relevant randomized clinical trials. The primary outcome was cardiovascular mortality, separately considering trials of beta-blockers versus placebo and beta-blockers versus other antianginals. We conducted a subgroup analysis on cardioselective versus non-cardioselective beta-blockers and calcium channel antagonists versus nitrates. We calculated odds ratios (ORs) and confidence intervals (CIs) using Peto's method. We found no statistically significant evidence that beta-blockers impact on mortality when compared with placebo (OR, 0.42; CI, 0.15–1.21) or other antianginals (OR, 0.98; CI, 0.86–1.10), or all others (OR, 0.97; CI, 0.86–1.09). There was a trend for cardioselective beta-blockers to have a greater improvement in mortality when compared with placebo and to have greater impact than non-calcium channel antagonists. Beta-blockers do not have statistically significant impact on mortality versus placebo or versus other active comparators. The findings exclude a benefit of 15% or greater and a hazard of 10% or greater. The impact of cardioselectivity requires further study.
Musculoskeletal sequelae of Varicella-zoster infection: two case reports
Authors: Lim J B T , Huntley J S
Published: May 2012

Varicella-zoster is a common paediatric viral infection that usually runs a benign self-limiting course but has a risk of complications. The most common sequelae are bacterial skin infections, which are usually mild. However, bacteraemia/septic shock, toxic shock syndrome, pneumonia, ataxia, encephalitis and purpura fulminans are also possible. Although rare, musculoskeletal sequelae (osteomyelitis, septic arthritis, pyomyositis and necrotizing fasciitis) can occur in otherwise healthy children. These latter complications are potentially life- and limb-threatening and must be considered in a child post-varicella with pain in a limb or joint. We describe two patients who had musculoskeletal complications after varicella: (1) a 16-month-old boy who developed pyomyositis of the thigh and septic arthritis of the hip and (2) a two-year-seven-month-old girl who developed septic arthritis of the hip and knee and a ‘bare area’ subperiosteal abscess of the femur. Their clinical presentations, detailed management plans and outcomes are reported. These cases highlight the importance of prompt diagnosis, appropriate investigation (including the important role of magnetic resonance imaging) and surgery when an otherwise healthy post-varicella child deteriorates.
Dry eyes can be exacerbated by systemic antihypertensive medication
Authors: Sagili S , Malhotra R
Published: May 2012

Dry eye disease (DED) is a frequent problem in ophthalmology, causing considerable morbidity. DED is a multifactorial disease and requires a comprehensive approach in identifying the potential contributing factors. Often, clinicians overlook the fact that systemic medications are a cause of dry eye. We report two patients who developed symptoms and signs of DED secondary to systemic antihypertensive medication that improved following cessation of systemic medication.
Synchronous bilateral infiltrating syringomatous adenoma of the breast
Authors: Mrklić I , Bezić J , Pogorelić Z , Ilić N , Tadić T , Buljević V , Tomić S
Published: May 2012

Infiltrating syringomatous breast adenoma is an uncommon mammary neoplasm composed of angulated glandular structures with a variable amount of epidermoid differentiation which proliferate in a background of dense collagenous stroma. The patient presented with bilateral hardness and oedema of the nipples. Ultrasound and mammography revealed microcalcifications in retromammilary regions of both nipples. Histological examination of the resected specimens showed angulated glands and solid cords, lined by an inner layer of epithelial cells and an outer layer of myoepithelial cells, immersed in desmoplastic stroma. Within the solid cords reminiscent of squamous cells, occasionally aggregated in keratinizing cysts were found. To the best of our knowledge this is the first described case of bilateral infiltrating syringomatous breast adenoma with synchronous presentation. Infiltrating syringomatous adenoma is a rare lesion. A finding of infiltrating syringomatous adenoma in one breast should prompt careful examination of the opposite breast with adequate follow-up.
Boerhaave's syndrome secondary to gastric volvulus
Authors: Paily A , Patel D , Lamb P
Published: May 2012

Boerhaave's syndrome is oesophageal rupture as a result of forceful vomiting or retching against a closed cricopharyngeus. We report the case of an 81-year-old man with oesophageal rupture secondary to volvulus of an intrathoracic stomach who underwent laparotomy with a repair of the oesophageal perforation and intrathoracic stomach, making a good recovery. This case demonstrates another life-threatening complication of an intrathoracic stomach and highlights the importance of an early diagnosis and the advantages of using a transabdominal approach in this situation.
Early clinical experience with the Anaconda re-deployable endograft in 106 patients with abdominal aortic aneurism: the west of Scotland Anaconda registry
Authors: Majumder B , Urquhart G , Edwards R , Irshad K , Velu R , Reid D B
Published: May 2012

Endovascular repair of abdominal aortic aneurysm is a common procedure and not without complications. The aim of this study was to evaluate the early results of the Anaconda endograft (Vascutek Ltd., Inchinnan, Scotland, UK) in 106 patients in three hospitals in the west of Scotland. A prospective registry of 106 consecutive patients undergoing endoluminal repair of their abdominal aortic aneurysms using the Anaconda device was set up to record the clinical outcomes, with a mean follow-up of two years. There was no 30-day perioperative mortality in the 106 patients. Only type II endoleaks were detected on serial computed tomography scanning at follow-up. Technical success was achieved in 99% (105/106) in this study; one patient was converted to open surgical repair. Two cases of proximal device migration (>1 cm) were detected at one month and 19 months, respectively, with no associated endoleak or sac enlargement. Five cases of endograft limb thrombosis were noted in this study. Our early clinical experience with the Anaconda endograft compares favourably with other commercially available endografts in the treatment of abdominal aortic aneurysms. The main advantages of this device are that it is re-deployable and that it has a magnetic wire system which makes it easy to implant.
Elective paediatric surgery: what do parents really want to know?
Authors: Niyogi A , Clarke S A
Published: May 2012

The views of the parents of children undergoing elective surgery are not well represented in the literature. The aim of this study was to identify the priorities of parents with a view to improve their satisfaction. A questionnaire-based survey was conducted among parents of children undergoing elective surgery between November 2007 and March 2008. A total of 337 completed questionnaires were received. A similar survey was conducted among 12 surgeons, and their views were compared. Forty-three percent of parents preferred to know about a procedure on the day of surgery while others wanted the information in advance. Parents were most concerned with the complications of surgery and least concerned with the scar. Most of the surgeons thought it was not essential to mention their level of experience and the detailed surgical procedure to the parents while obtaining consent for surgery. In contrast, the parents thought that knowing the experience of the operating surgeon and the detailed surgical procedure was more important than knowing the duration of operation and the surgical incision. Face-to-face discussion with a surgeon was the most preferred mode of communication. Although 82% of parents have access to the Internet, booklets were more popular among parents than online information. Twelve percent of parents wanted the information in a foreign language. This survey reveals the perspective of parents about their child's surgery and identifies the differences in opinion between patients and surgeons about the information to be provided before surgery. Tailoring information to the parents’ priorities will improve parent satisfaction.
Rosuvastatin might have an effect on C-reactive protein but not on rheumatoid disease activity: Tayside randomized controlled study
Authors: Kumar P , Kennedy G , Khan F , Pullar T , Belch J J F
Published: May 2012

The aim of this study was to study the effects of rosuvastatin in patients with rheumatoid arthritis (RA) looking at the C-reactive protein (CRP), interleukin-6 (IL-6) and joint disease activity. Fifty RA patients were randomized in a double-blind placebo-controlled trial to receive either 10 mg of rosuvastatin or placebo as an adjunct to existing disease-modifying antirheumatic therapy. Patients were followed up for a six-month period. Measurements were done at baseline and six months. CRP and IL-6 were measured in the blood. RA disease activity was measured using disease activity score based on 28 joint counts (DAS 28). When analysing from baseline to six months there was no difference between the rosuvastatin and placebo groups in rheumatoid disease activity (–0.01; standard deviation [SD], 1.08; and +0.18; SD, 0.95; respectively; P value 0.509). There was a trend towards improvement in CRP in the rosuvastatin group (–3.23; SD, 18.18) compared with the placebo group (+17.43; SD, 38.03); P value, 0.161. IL-6 showed a trend towards worsening in the rosuvastatin group (+0.15; SD, 1.09) compared with placebo (–0.73; SD, 1.4); P value, 0.054. These data show that rosuvastatin with might decrease the CRP independent to IL-6 in patients with RA but does not improve the overall rheumatoid disease activity.