bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overweight worsens apoptosis, neuroinflammation and blood-brain barrier damage after hypoxic ischemia in neonatal brain through JNK hyperactivation
Authors: Tu Yi-Fang , Tsai Yau-Sheng , Wang Lan-Wan , Wu Hsin-Chieh , Huang Chao-Ching , Ho Chien-Jung 
Published: April 2011

Abstract

Background
Apoptosis, neuroinflammation and blood-brain barrier (BBB) damage affect the susceptibility of the developing brain to hypoxic-ischemic (HI) insults. c-Jun N-terminal kinase (JNK) is an important mediator of insulin resistance in obesity. We hypothesized that neonatal overweight aggravates HI brain damage through JNK hyperactivation-mediated upregulation of neuronal apoptosis, neuroinflammation and BBB leakage in rat pups.

Methods
Overweight (OF) pups were established by reducing the litter size to 6, and control (NF) pups by keeping the litter size at 12 from postnatal (P) day 1 before HI on P7. Immunohistochemistry and immunoblotting were used to determine the TUNEL-(+) cells and BBB damage, cleaved caspase-3 and poly (ADP-ribose) polymerase (PARP), and phospho-JNK and phospho-BimEL levels. Immunofluorescence was performed to determine the cellular distribution of phospho-JNK.

Results
Compared with NF pups, OF pups had a significantly heavier body-weight and greater fat deposition on P7. Compared with the NF-HI group, the OF-HI group showed significant increases of TUNEL-(+) cells, cleaved levels of caspase-3 and PARP, and ED1-(+) activated microglia and BBB damage in the cortex 24 hours post-HI. Immunofluorescence of the OF-HI pups showed that activated-caspase 3 expression was found mainly in NeuN-(+) neurons and RECA1-(+) vascular endothelial cells 24 hours post-HI. The OF-HI group also had prolonged escape latency in the Morris water maze test and greater brain-volume loss compared with the NF-HI group when assessed at adulthood. Phospho-JNK and phospho-BimEL levels were higher in OF-HI pups than in NF-HI pups immediately post-HI. JNK activation in OF-HI pups was mainly expressed in neurons, microglia and vascular endothelial cells. Inhibiting JNK activity by AS601245 caused more attenuation of cleaved caspase-3 and PARP, a greater reduction of microglial activation and BBB damage post-HI, and significantly reduced brain damage in OF-HI than in NF-HI pups.

Conclusions
Neonatal overweight increased HI-induced neuronal apoptosis, microglial activation and BBB damage, and aggravated HI brain damage in rat pups through JNK hyperactivation.
Improving the prediction of yeast protein function using weighted protein-protein interactions
Authors: Ahmed Khaled S , Saloma Nahed H , Kadah Yasser M 
Published: April 2011

Abstract

Background
Bioinformatics can be used to predict protein function, leading to an understanding of cellular activities, and equally-weighted protein-protein interactions (PPI) are normally used to predict such protein functions. The present study provides a weighting strategy for PPI to improve the prediction of protein functions. The weights are dependent on the local and global network topologies and the number of experimental verification methods. The proposed methods were applied to the yeast proteome and integrated with the neighbour counting method to predict the functions of unknown proteins.

Results
A new technique to weight interactions in the yeast proteome is presented. The weights are related to the network topology (local and global) and the number of identified methods, and the results revealed improvement in the sensitivity and specificity of prediction in terms of cellular role and cellular locations. This method (new weights) was compared with a method that utilises interactions with the same weight and it was shown to be superior.

Conclusions
A new method for weighting the interactions in protein-protein interaction networks is presented. Experimental results concerning yeast proteins demonstrated that weighting interactions integrated with the neighbor counting method improved the sensitivity and specificity of prediction in terms of two functional categories: cellular role and cell locations.
Sequence characteristics of T4-like bacteriophage IME08 genome termini revealed by high throughput sequencing
Authors: Jiang Xiaofang , Jiang Huanhuan , Li Cun , Wang Sheng , Mi Zhiqiang , An Xiaoping , Chen Jiankui , Tong Yigang 
Published: April 2011

Abstract

Background
T4 phage is a model species that has contributed broadly to our understanding of molecular biology. T4 DNA replication and packaging share various mechanisms with human double-stranded DNA viruses such as herpes virus. The literature indicates that T4-like phage genomes have permuted terminal sequences, and are generated by a DNA terminase in a sequence-independent manner;

Methods
genomic DNA of T4-like bacteriophage IME08 was subjected to high throughput sequencing, and the read sequences with extraordinarily high occurrences were analyzed;

Results
we demonstrate that both the 5' and 3' termini of the IME08 genome starts with base G or A. The presence of a consensus sequence TTGGA|G around the breakpoint of the high frequency read sequences suggests that the terminase cuts the branched pre-genome in a sequence-preferred manner. Our analysis also shows that terminal cleavage is asymmetric, with one end cut at a consensus sequence, and the other end generated randomly. The sequence-preferred cleavage may produce sticky-ends, but with each end being packaged with different efficiencies;

Conclusions
this study illustrates how high throughput sequencing can be used to probe replication and packaging mechanisms in bacteriophages and/or viruses.
Molecular detection of multiple viral targets in untreated urban sewage from Greece
Authors: Kokkinos Petros A , Ziros Panos G , Mpalasopoulou Αggeliki , Galanis Alexis , Vantarakis Apostolos 
Published: April 2011

Abstract

Background
Urban sewage virological analysis may produce important information about the strains that cause clinical and subclinical infections in the population, thus supporting epidemiological studies.

Methods
In the present study, a twenty one-month survey (November 2007 to July 2009) was conducted in order to evaluate the presence of human adenoviruses (hAdV), hepatitis A viruses (HAV), hepatitis E viruses (HEV), Noroviruses (NoV), and human Polyomaviruses (hPyV) in untreated sewage samples collected from the inlet of Patras' municipal biological wastewater treatment plant, located in southwestern Greece. Nucleic acid amplification techniques were applied for viral nucleic acid detection. Positive samples were confirmed by sequencing and comparative phylogenetic analysis was performed on the isolated viral strains.

Results
In total, viruses were detected in 87.5% (42/48) of sewage samples. AdVs, PyVs, HAV, and NoVs were detected in 45.8% (22/48), 68.8% (33/48), 8.3% (4/48), and 6.3% (3/48) of the samples collected from the plant's inlet, while HEV was not detected at all. Adenovirus types 8 (Ad8), 40 (Ad40) and 41 (Ad41) were recognized, while JC and BK polyomaviruses were recorded. Noroviruses were identified as GII.4. HAV was typed as genotype IA.

Conclusions
Our study demonstrates the advantages of environmental surveillance as a tool to elucidate the molecular epidemiology of community circulating viruses. We underline the need of environmental surveillance programs in countries such as Greece with inadequate and problematic epidemiological surveillance system and no environmental surveillance system currently in action.
Multimodal Assessment of Painful Peripheral Neuropathy Induced by Chronic Oxaliplatin-Based Chemotherapy in Mice
Authors: Renn Cynthia L , Carozzi Valentina A , Rhee Peter , Gallop Danisha , Dorsey Susan G , Cavaletti Guido 
Published: April 2011

Background: A major clinical issue affecting 10-40% of cancer patients treated with oxaliplatin is severe peripheral neuropathy with symptoms including cold sensitivity and neuropathic pain. Rat models have been used to describe the pathological features of oxaliplatin-induced peripheral neuropathy; however, they are inadequate for parallel studies of oxaliplatin's antineoplastic activity and neurotoxicity because most cancer models are developed in mice. Thus, we characterized the effects of chronic, bi-weekly administration of oxaliplatin in BALB/c mice. We first studied oxaliplatin's effects on the peripheral nervous system by measuring caudal and digital nerve conduction velocities (NCV) followed by ultrastructural and morphometric analyses of dorsal root ganglia (DRG) and sciatic nerves. To further characterize the model, we examined nocifensive behavior and central nervous system excitability by in vivo electrophysiological recording of spinal dorsal horn (SDH) wide dynamic range neurons in oxaliplatin-treated mice Results: We found significantly decreased NCV and action potential amplitude after oxaliplatin treatment along with neuronal atrophy and multinucleolated DRG neurons that have eccentric nucleoli. Oxaliplatin also induced significant mechanical allodynia and cold hyperalgesia, starting from the first week of treatment, and a significant increase in the activity of wide dynamic range neurons in the SDH. Conclusions: Our findings demonstrate that chronic treatment with oxaliplatin produces neurotoxic changes in BALB/c mice, confirming that this model is a suitable tool to conduct further mechanistic studies of oxaliplatin-related antineoplastic activity, peripheral neurotoxicity and pain. Further, this model can be used for the preclinical discovery of new neuroprotective and analgesic compounds.
Value of diffusion weighted MR imaging as an early surrogate parameter for evaluation of tumor response to high-dose-rate brachytherapy of colorectal liver metastases
Authors: Wybranski Christian , Zeile Martin , Löwenthal David , Fischbach Frank , Pech Maciej , Röhl Friedrich-Wilhelm , Gademann Günther , Ricke Jens , Dudeck Oliver 
Published: April 2011

Abstract

Background
To assess the value of diffusion weighted imaging (DWI) as an early surrogate parameter for treatment response of colorectal liver metastases to image-guided single-fraction 192Ir-high-dose-rate brachytherapy (HDR-BT).

Methods
Thirty patients with a total of 43 metastases underwent CT- or MRI-guided HDR-BT. In 13 of these patients a total of 15 additional lesions were identified, which were not treated at the initial session and served for comparison. Magnetic resonance imaging (MRI) including breathhold echoplanar DWI sequences was performed prior to therapy (baseline MRI), 2 days after HDR-BT (early MRI) as well as after 3 months (follow-up MRI). Tumor volume (TV) and intratumoral apparent diffusion coefficient (ADC) were measured independently by two radiologists. Statistical analysis was performed using univariate comparison, ANOVA and paired t test as well as Pearson's correlation.

Results
At early MRI no changes of TV and ADC were found for non-treated colorectal liver metastases. In contrast, mean TV of liver lesions treated with HDR-BT increased by 8.8% (p = 0.054) while mean tumor ADC decreased significantly by 11.4% (p < 0.001). At follow-up MRI mean TV of non-treated metastases increased by 50.8% (p = 0.027) without significant change of mean ADC values. In contrast, mean TV of treated lesions decreased by 47.0% (p = 0.026) while the mean ADC increased inversely by 28.6% compared to baseline values (p < 0.001; Pearson's correlation coefficient of r = -0.257; p < 0.001).

Conclusions
DWI is a promising imaging biomarker for early prediction of tumor response in patients with colorectal liver metastases treated with HDR-BT, yet the optimal interval between therapy and early follow-up needs to be elucidated.
Longitudinal evaluation the pulmonary function of the pre and postoperative periods in the coronary artery bypass graft surgery of patients treated with a physiotherapy protocol
Authors: Moreno Adalgiza M , Castro Renata RT , Sorares Pedro PS , Anna Mauricio Sant' , Cravo Sergio LD , Nóbrega Antônio CL 
Published: April 2011

Abstract

Background
The treatment of coronary artery disease (CAD) seeks to reduce or prevent its complications and decrease morbidity and mortality. For certain subgroups of patients, coronary artery bypass graft surgery (CABG) may accomplish these goals. The objective of this study was to assess the pulmonary function in the CABG postoperative period of patients treated with a physiotherapy protocol.

Methods
Forty-two volunteers with an average age of 63 ± 2 years were included and separated into three groups: healthy volunteers (n = 09), patients with CAD (n = 9) and patients who underwent CABG (n = 20). Patients from the CABG group received preoperative and postoperative evaluations on days 3, 6, 15 and 30. Patients from the CAD group had evaluations on days 1 and 30 of the study, and the healthy volunteers were evaluated on day 1. Pulmonary function was evaluated by measuring forced vital capacity (FVC), maximum expiratory pressure (MEP) and Maximum inspiratory pressure (MIP).

Results
After CABG, there was a significant decrease in pulmonary function (p < 0.05), which was the worst on postoperative day 3 and returned to the preoperative baseline on postoperative day 30.

Conclusion
Pulmonary function decreased after CABG. Pulmonary function was the worst on postoperative day 3 and began to improve on postoperative day 15. Pulmonary function returned to the preoperative baseline on postoperative day 30.
A mutation in the dynein heavy chain gene compensates for energy deficit of mutant SOD1 mice and increases potentially neuroprotective IGF-1
Authors: Fergani Anissa , Eschbach Judith , Oudart Hugues , Larmet Yves , Schwalenstocker Birgit , Ludolph Albert C , Loeffler Jean-Philippe , Dupuis Luc 
Published: April 2011

Abstract

Background
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive loss of motor neurons. ALS patients, as well as animal models such as mice overexpressing mutant SOD1s, are characterized by increased energy expenditure. In mice, this hypermetabolism leads to energy deficit and precipitates motor neuron degeneration. Recent studies have shown that mutations in the gene encoding the dynein heavy chain protein are able to extend lifespan of mutant SOD1 mice. It remains unknown whether the protection offered by these dynein mutations relies on a compensation of energy metabolism defects.

Results
SOD1(G93A) mice were crossbred with mice harboring the dynein mutant Cramping allele (Cra/+ mice). Dynein mutation increased adipose stores in compound transgenic mice through increasing carbohydrate oxidation and sparing lipids. Metabolic changes that occurred in double transgenic mice were accompanied by the normalization of the expression of key mRNAs in the white adipose tissue and liver. Furthermore, Dynein Cra mutation rescued decreased post-prandial plasma triglycerides and decreased non esterified fatty acids upon fasting. In SOD1(G93A) mice, the dynein Cra mutation led to increased expression of IGF-1 in the liver, increased systemic IGF-1 and, most importantly, to increased spinal IGF-1 levels that are potentially neuroprotective.

Conclusions
These findings suggest that the protection against SOD1(G93A) offered by the Cramping mutation in the dynein gene is, at least partially, mediated by a reversal in energy deficit and increased IGF-1 availability to motor neurons.
Improving prehospital trauma management for skiers and snowboarders - need for on-slope triage?
Authors: Hasler Rebecca M , Schmucker Uli , Evangelopoulos Dimitrios S , Hirschberg Ron E , Zimmermann Heinz , Exadaktylos Aristomenis K 
Published: April 2011

Abstract

Background
Injuries from skiing and snowboarding became a major challenge for emergency care providers in Switzerland. In the alpine setting, early assessment of injury and health status is essential for the initiation of adequate means of care and transport. Nevertheless, validated standardized protocols for on-slope triage are missing. This article can assist in understanding the characteristics of injured winter sportsmen and exigencies for future on-slope triage protocols.

Methods
Six-year review of trauma cases in a tertiary trauma centre. Consecutive inclusion of all injured skiers and snowboarders aged >15 (total sample) years with predefined, severe injury to the head, spine, chest, pelvis or abdomen (study sample) presenting at or being transferred to the study hospital. Descriptive analysis of age, gender and injury pattern.

Results
Amongst 729 subjects (total sample) injured from skiing or snowboarding, 401 (55%, 54% of skiers and 58% of snowboarders) suffered from isolated limb injury. Amongst the remaining 328 subjects (study sample), the majority (78%) presented with monotrauma. In the study sample, injury to the head (52%) and spine (43%) was more frequent than injury to the chest (21%), pelvis (8%), and abdomen (5%). The three most frequent injury combinations were head/spine (10% of study sample), head/thorax (9%), and spine/thorax (6%). Fisher's exact test demonstrated an association for injury combinations of head/thorax (p < 0.001), head/abdomen (p = 0.019), and thorax/abdomen (p < 0.001).

Conclusion
The data presented and the findings from previous investigations indicate the need for development of dedicated on-slope triage protocols. Future research must address the validity and practicality of diagnostic on-slope tests for rapid decision making by both professional and lay first responders. Thus, large-scale and detailed injury surveillance is the future research priority.
An imbalance in progenitor cell populations reflects tumour progression in breast cancer primary culture models
Authors: Donatello Simona , Hudson Lance , Cottell David C , Blanco Alfonso , Aurrekoetxea Igor , Shelly Martin J , Dervan Peter A , Kell Malcolm R , Stokes Maurice , Hill Arnold DK , Hopkins Ann M 
Published: April 2011

AbstractBackgroundMany factors influence breast cancer progression, including the ability of progenitor cells to sustain or increase net tumour cell numbers. Our aim was to define whether alterations in putative progenitor populations could predict clinicopathological factors of prognostic importance for cancer progression.MethodsPrimary cultures were established from human breast tumour and adjacent non-tumour tissue. Putative progenitor cell populations were isolated based on co-expression or concomitant absence of the epithelial and myoepithelial markers EPCAM and CALLA respectively.ResultsSignificant reductions in cellular senescence were observed in tumour versus non-tumour cultures, accompanied by a stepwise increase in proliferation:senescence ratios. A novel correlation between tumour aggressiveness and an imbalance of putative progenitor subpopulations was also observed. Specifically, an increased double-negative (DN) to double-positive (DP) ratio distinguished aggressive tumours of high grade, estrogen receptor-negativity or HER2-positivity. The DN:DP ratio was also higher in malignant MDA-MB-231 cells relative to non-tumourogenic MCF-10A cells. Ultrastructural analysis of the DN subpopulation in an invasive tumour culture revealed enrichment in lipofuscin bodies, markers of ageing or senescent cells.ConclusionsOur results suggest that an imbalance in tumour progenitor subpopulations imbalances the functional relationship between proliferation and senescence, creating a microenvironment favouring tumour progression.
MUC4 stabilizes HER2 expression and maintains the cancer stem cell population in ovarian cancer cells
Authors: Ponnusamy Moorthy P , Seshacharyulu Parthasarathy , Vaz ArokiaPriyanka , Dey Parama , Batra Surinder K 
Published: April 2011

Abstract

Background
Recent evidence has suggested that the capability of cancer to grow, propagate and relapse after therapy is dependent on a small subset of the cell population within the tumor, called cancer stem cells. Therefore, this subpopulation of cells needs to be targeted with different approaches by identification of unique stem-cell specific target antigens. One of the well known tumor antigens is the epithelial cell mucin MUC4, which is aberrantly expressed in ovarian cancer as compared to the normal ovary and plays a pivotal role in the aggressiveness and metastasis of ovarian cancer cells. In the present study, we aimed to analyze the cancer stem cell population in MUC4 overexpressed ovarian cancer cells.

Methods
MUC4 was ectopically overexpressed in SKOV3 ovarian cancer cells. Western blot analysis was performed for MUC4, HER2, CD133, ALDH1 and Shh expression in MUC4 overexpressed cells. Confocal analysis of MUC4, HER2 and CD133 was also done in the MUC4 overexpressed cells. CD133 and Hoechst33342 dye staining was used to analyze the cancer stem cell population via FACS method in SKOV3-MUC4 cells.

Results
MUC4 overexpressed SKOV3 cells showed an increased expression of HER2 compared to control cells. MUC4 overexpression leads to increased (0.1%) side population (SP) and CD133-positive cancer stem cells compared to the control cells. Interestingly, the tumor sphere type circular colony formation was observed only in the MUC4 overexpressed ovarian cancer cells. Furthermore, the cancer stem cell marker CD133 was expressed along with MUC4 in the isolated circular colonies as analyzed by both confocal and western blot analysis. HER2 and cancer stem cell specific marker ALDH1 along with Shh, a self-renewal marker, showed increased expression in the isolated circular colonies compared to MUC4-transfected cells.

Conclusion
These studies demonstrate that MUC4 overexpression leads to an enriched ovarian cancer stem cell population either directly or indirectly through HER2. In future, this study would be helpful for MUC4-directed therapy for the ovarian cancer stem cell population.
Clinical relevance of findings in trials of antipsychotics: systematic review
Authors: Lepping Peter , Sambhi Rajvinder S. , Whittington Richard , Lane Steven , Poole Rob 
Published: April 2011

BackgroundThere is concern over the methods used to evaluate antipsychotic drugs.AimsTo assess the clinical relevance of findings in the literature.MethodA systematic review identified studies of antipsychotics that used the Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale (PANSS). A published method of translating these into Clinical Global Impression – Change scale (CGI–C) scores was used to measure clinical relevance.ResultsIn total 98 data-sets were included in the BPRS analysis and 202 data-sets in the PANSS analysis. When aggregated scores were translated into notional CGI–C scores, most drugs reached ‘minimal improvement’ on the BPRS, but few reached that level for PANSS. This was true of both first- and second-generation drugs, including clozapine. Amisulpride and olanzapine had better than average CGI–C scores.ConclusionsOur findings show improvements of limited clinical relevance. The CGI–C scores were better for the BPRS than for the PANSS.