bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome–positive chronic myeloid leukemia patients with resistance or intolerance to imatinib
Authors: Cortes Jorge E. , Kantarjian Hagop M. , Brümmendorf Tim H. , Kim Dong-Wook , Turkina Anna G. , Shen Zhi-Xiang , Pasquini Ricardo , Khoury H. Jean , Arkin Steven , Volkert Angela , Besson Nadine , Abbas Richat , Wang Junyuan , Leip Eric , Gambacorti-Passerini Carlo
Published: August 2011

Bosutinib, a dual Src/Abl kinase inhibitor, has shown potent activity against chronic myeloid leukemia (CML). In this phase 1/2 study we evaluated bosutinib in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. Part 1 was a dose-escalation study to determine the recommended starting dose for part 2; part 2 evaluated the efficacy and safety of bosutinib 500 mg once-daily dosing. The study enrolled 288 patients with imatinib-resistant (n = 200) or imatinibintolerant (n = 88) CML and no other previous kinase inhibitor exposure. At 24 weeks, 31% of patients achieved major cytogenetic response (primary end point). After a median follow-up of 24.2 months, 86% of patients achieved complete hematologic remission, 53% had a major cytogenetic response (41% had a complete cytogenetic response), and 64% of those achieving complete cytogenetic response had a major molecular response. At 2 years, progression-free survival was 79%; overall survival at 2 years was 92%. Responses were seen across Bcr-Abl mutants, except T315I. Bosutinib exhibited an acceptable safety profile; the most common treatment-emergent adverse event was mild/moderate, typically self-limiting diarrhea. Grade 3/4 nonhematologic adverse events (> 2% of patients) included diarrhea (9%), rash (9%), and vomiting (3%). These data suggest bosutinib is effective and tolerable in patients with chronic phase imatinib-resistant or imatinib-intolerant CML. This trial was registered at http://www.clinicaltrials.gov as NCT00261846.
Roles of planar cell polarity pathways in the development of neutral tube defects
Authors: Wu Gang , Huang Xupei , Hua Yimin , Mu Dezhi
Published: August 2011

Neural tube defects (NTDs) are the second most common birth defect in humans. Despite many advances in the understanding of NTDs and the identification of many genes related to NTDs, the fundamental etiology for the majority of cases of NTDs remains unclear. Planar cell polarity (PCP) signaling pathway, which is important for polarized cell movement (such as cell migration) and organ morphogenesis through the activation of cytoskeletal pathways, has been shown to play multiple roles during neural tube closure. The disrupted function of PCP pathway is connected with some NTDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of NTDs.
The contribution of water contact behavior to the high Schistosoma mansoni Infection rates observed in the Senegal River Basin
Authors: Sow Seydou , de Vlas Sake J , Stelma Foekje , Vereecken Kim , Gryseels Bruno , Polman Katja
Published: August 2011

Background

Schistosomiasis is one of the major parasitic diseases in the world in terms of people infected and those at risk. Infection occurs through contact with water contaminated with larval forms of the parasite, which are released by freshwater snails and then penetrate the skin of people. Schistosomiasis infection and human water contact are thus essentially linked, and more knowledge about their relationship will help us to develop appropriate control measures. So far, only few studies have related water contact patterns to infection levels.

Methods

We have conducted detailed direct water contact observations in a village in Northern Senegal during the first years of a massive Schistosoma mansoni outbreak to determine the role of human water contact in the extent of the epidemic.

We quantified water contact activities in terms of frequency and duration, and described how these vary with age and sex. Moreover, we assessed the relationship between water contact- and infection intensity patterns to further elucidate the contribution of exposure to the transmission of schistosomiasis.

Results

This resulted in over 120,000 recorded water contacts for 1651 subjects over 175 observation days. Bathing was the main activity, followed by household activities. Frequency and duration of water contact depended on age and sex rather than season. Water contacts peaked in adolescents, women spent almost twice as much time in the water as men, and water contacts were more intense in the afternoon than in the morning, with sex-specific intensity peaks. The average number of water contacts per person per day in this population was 0.42; the average time spent in the water per person per day was 4.3 minutes.

Conclusions

The observed patterns of water contact behavior are not unusual and have been described before in various other settings in sub-Saharan Africa. Moreover, water contact levels were not exceptionally high and thus cannot explain the extremely high S. mansoni infection intensities as observed in Northern Senegal. Comparison with fecal egg counts in the respective age and sex groups further revealed that water contact levels did not unambiguously correspond with infection levels, indicating that factors other than exposure also play a role in determining intensity of infection.
Purine Nucleoside Phosphorylase mediated molecular chemotherapy and conventional chemotherapy: A tangible union against chemoresistant cancer
Authors: Singh Preetinder P , Joshi Swapna , Russell Pamela J , Nair Sham , Khatri Aparajita
Published: August 2011

Background

Late stage Ovarian Cancer is essentially incurable primarily due to late diagnosis and its inherent heterogeneity. Single agent treatments are inadequate and generally lead to severe side effects at therapeutic doses. It is crucial to develop clinically relevant novel combination regimens involving synergistic modalities that target a wider repertoire of cells and lead to lowered individual doses. Stemming from this premise, this is the first report of two- and three-way synergies between Adenovirus-mediated Purine Nucleoside Phosphorylase based gene directed enzyme prodrug therapy (PNP-GDEPT), docetaxel and/or carboplatin in multidrug-resistant ovarian cancer cells.

Methods

The effects of PNP-GDEPT on different cellular processes were determined using Shotgun Proteomics analyses. The in vitro cell growth inhibition in differentially treated drug resistant human ovarian cancer cell lines was established using a cell-viability assay. The extent of synergy, additivity, or antagonism between treatments was evaluated using CalcuSyn statistical analyses. The involvement of apoptosis and implicated proteins in effects of different treatments was established using flow cytometry based detection of M30 (an early marker of apoptosis), cell cycle analyses and finally western blot based analyses.

Results

Efficacy of the trimodal treatment was significantly greater than that achieved with bimodal- or individual treatments with potential for 10-50 fold dose reduction compared to that required for individual treatments. Of note was the marked enhancement in apoptosis that specifically accompanied the combinations that included PNP-GDEPT and accordingly correlated with a shift in the expression of anti- and pro-apoptotic proteins. PNP-GDEPT mediated enhancement of apoptosis was reinforced by cell cycle analyses. Proteomic analyses of PNP-GDEPT treated cells indicated a dowregulation of proteins involved in oncogenesis or cancer drug resistance in treated cells with accompanying upregulation of apoptotic- and tumour- suppressor proteins.

Conclusion

Inclusion of PNP-GDEPT in regular chemotherapy regimens can lead to significant enhancement of the cancer cell susceptibility to the combined treatment. Overall, these data will underpin the development of regimens that can benefit patients with late stage ovarian cancer leading to significantly improved efficacy and increased quality of life.
Clinical management of gastric cancer: results of a multicentre survey
Authors: Zhang Xiaolong , Li Nanjing , Wei Wen , Yao Wenxiu , Xie Ke , Hu Jiankun , Shen Lida , Ji Weizheng , Lu You , Wen Feng , Jiang Yu , Xu Feng , Feng Hong , Bi Feng , Li Qiu ,   The Western Cooperative Gastrointestinal Oncology Group of China
Published: August 2011

Background

The National Comprehensive Cancer Network clinical practice guidelines in oncology-gastric cancer guidelines have been widely used to provide appropriate recommendations for the treatment of patients with gastric cancer. The aim of this study was to examine the adherence of surgical oncologists, medical oncologists, and radiation oncologists' to the recommended guidelines.

Methods

A questionnaire asking the treatment options for gastric cancer cases was sent to 394 Chinese oncology specialists, including surgical oncologists, medical oncologists, and radiation oncologists working in hospitals joined in The Western Cooperative Gastrointestinal Oncology Group of China. The questionnaire involved a series of clinical scenarios regarding the interpretation of surgery, neoadjuvant, adjuvant, and advanced treatment planning of gastric cancer.

Results

Analysis of 358 respondents (91%) showed variations between each specialization and from the recommended guidelines in the management approaches to specific clinical scenarios. The majority of specialists admitted that less than 50% of patients received multidisciplinary evaluation before treatment. The participants gave different responses to questions involving adjuvant, neoadjuvant, and advanced settings, compared to the recommended guidelines.

Conclusions

These results highlight the heterogeneity of the treatment of gastric cancer. Surgical oncologists, medical oncologists, and radiation oncologists are not adhering to the recommended guidelines.
Dimensionality and scale properties of the Edinburgh Depression Scale (EDS) in patients with type 2 diabetes mellitus: the DiaDDzoB study
Authors: de Cock Evi SA , Emons Wilco HM , Nefs Giesje , Pop Victor JM , Pouwer François
Published: August 2011

Background

Depression is a common complication in type 2 diabetes (DM2), affecting 10-30% of patients. Since depression is underrecognized and undertreated, it is important that reliable and validated depression screening tools are available for use in patients with DM2. The Edinburgh Depression Scale (EDS) is a widely used method for screening depression. However, there is still debate about the dimensionality of the test. Furthermore, the EDS was originally developed to screen for depression in postpartum women. Empirical evidence that the EDS has comparable measurement properties in both males and females suffering from diabetes is lacking however.

Methods

In a large sample (N = 1,656) of diabetes patients, we examined: (1) dimensionality; (2) gender-related item bias; and (3) the screening properties of the EDS using factor analysis and item response theory.

Results

We found evidence that the ten EDS items constitute a scale that is essentially one dimensional and has adequate measurement properties. Three items showed differential item functioning (DIF), two of them showed substantial DIF. However, at the scale level, DIF had no practical impact. Anhedonia (the inability to be able to laugh or enjoy) and sleeping problems were the most informative indicators for being able to differentiate between the diagnostic groups of mild and severe depression.

Conclusions

The EDS constitutes a sound scale for measuring an attribute of general depression. Persons can be reliably measured using the sum score. Screening rules for mild and severe depression are applicable to both males and females.
Effects of Hylan G-F 20 supplementation on cartilage preservation detected by magnetic resonance imaging in osteoarthritis of the knee: a two-year single-blind clinical trial
Authors: Wang Yuanyuan , Hall Stephen , Hanna Fahad , Wluka Anita E , Grant Gail , Marks Paul , Feletar Marie , Cicuttini Flavia M
Published: August 2011

Background

Although viscosupplementation is an effective symptomatic treatment for knee osteoarthritis (OA), the effect of longer term administration on articular cartilage has not been fully explored. We examined the effect of viscosupplementation with Hylan G-F 20 on knee cartilage over 2 years in patients with knee OA.

Methods

In this prospective, single-blind, parallel control group pilot study, 78 patients with symptomatic knee OA (Kellgren-Lawrence grade II and III) were assigned to either intervention group (n = 39 receiving 4 courses of 3 × 2.0 ml of intra-articular Hylan G-F 20 injections at 6 month intervals) or control group (n = 39 receiving usual care for knee OA without injections). Magnetic resonance imaging of the study knee was performed at baseline, 12 and 24 months. Cartilage volume and defects were assessed using validated methods.

Results

Fifty-five subjects (71%) completed 24 month follow up. Over 24 months, the intervention group had a reduced annual percentage rate of medial and lateral tibial cartilage volume loss (mean ± SD, -0.3 ± 2.7% and -1.4 ± 4.3%) compared with the control group (2.3 ± 2.6% and 1.4 ± 2.6%, P = 0.001 and 0.005 for difference, respectively). The intervention group also showed reduced cartilage defect score increment in the medial tibiofemoral compartment (0.1 ± 1.3) compared with the control group (0.8 ± 1.5, P = 0.05).

Conclusions

Six monthly intra-articular injections of Hylan G-F 20 administered to patients with symptomatic knee OA have a beneficial effect on knee cartilage preservation measured by both cartilage volume and cartilage defects. Hylan G-F 20 warrants further evaluation in larger clinical trials as a possible disease-modifying agent in the treatment of knee OA.

Trial Registration

The study was registered with ClinicalTrials.gov (NCT00393393).
Molecular markers of antifolate resistance in Plasmodium falciparum isolates from Luanda, Angola
Authors: Gama Bianca E , Pereira-Carvalho Guilhermina AL , Lutucuta Kosi Florbela JI , Almeida de Oliveira Natália K , Fortes Filomeno , Rosenthal Philip J , do Rosário Virgílio E , Daniel-Ribeiro Cláudio Tadeu , Fátima Ferreira-da-Cruz Maria de
Published: August 2011

Background

Plasmodium falciparum malaria remains a leading health problem in Africa and its control is seriously challenged by drug resistance. Although resistance to the sulphadoxine-pyrimethamine (SP) is widespread, this combination remains an important component of malaria control programmes as intermittent preventive therapy (IPT) for pregnant women and children. In Angola, resistance patterns have been poorly characterized, and IPT has been employed for pregnant women since 2006. The aim of this study was to assess the prevalence of key antifolate resistance mediating polymorphisms in the pfdhfr and pfdhps genes in P. falciparum samples from Angola.

Methods

Plasmodium falciparum samples collected in Luanda, in 2007, were genotyped by amplification and DNA forward and reverse sequencing of the pfdhfr and pfdhps genes.

Results

The most prevalent polymorphisms identified were pfdhfr 108N (100%), 51I (93%), 59R (57%) and pfdhps 437G (93%). Resistance-mediating polymorphisms in pfdhps less commonly observed in West Africa were also identified (540E in 10%, 581G in 7% of samples).

Conclusion

This study documents an important prevalence of 4 P. falciparum polymorphisms that predicts an antifolate resistance in Luanda. Further, some samples presented additional mutations associated to high-level resistance. These results suggest that the use of SP for IPT may no longer be warranted in Angola.
Exposure to arsenic in drinking water is associated with increased prevalence of diabetes: a cross-sectional study in the Zimapán and Lagunera regions in Mexico
Authors: Del Razo Luz M , García-Vargas Gonzalo G , Valenzuela Olga L , Castellanos Erika Hernández , Sánchez-Peña Luz C , Currier Jenna M , Drobná Zuzana , Loomis Dana , Stýblo Miroslav
Published: August 2011

Background

Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico.

Methods

We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity.

Results

The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance.

Conclusions

Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII.
Combination of cyclosporine and erythropoietin improves brain infarct size and neurological function in rats after ischemic stroke
Authors: Yuen Chun-Man , Sun Cheuk-Kwan , Lin Yu-Chun , Chang Li-Teh , Kao Ying-Hsien , Yen Chia-Hung , Chen Yung-Lung , Tsai Tzu-Hsien , Chua Sarah , Shao Pei-Lin , Leu Steve , Yip Hon-Kan
Published: August 2011

Background

This study tested the superiority of combined cyclosporine A (CsA)-erythropoietin (EPO) therapy compared with either one in limiting brain infarction area (BIA) and preserving neurological function in rat after ischemic stroke (IS).

Methods

Fifty adult-male SD rats were equally divided into sham control (group 1), IS plus intra-peritoneal physiological saline (at 0.5/24/48 h after IS) (group 2), IS plus CsA (20.0 mg/kg at 0.5/24h, intra-peritoneal) (group 3), IS plus EPO (5,000IU/kg at 0.5/24/48h, subcutaneous) (group 4), combined CsA and EPO (same route and dosage as groups 3 and 4) treatment (group 5) after occlusion of distal left internal carotid artery.

Results

BIA on day 21 after acute IS was higher in group 2 than in other groups and lowest in group 5 (all p < 0.01). The sensorimotor functional test showed higher frequency of left turning in group 2 than in other groups and lowest in group 5 (all p < 0.05). mRNA and protein expressions of apoptotic markers and number of apoptotic nuclei on TUNEL were higher in group 2 than in other groups and lowest in group 1 and 5, whereas the anti-apoptotic markers exhibited an opposite trend (all p < 0.05). The expressions of inflammatory and oxidized protein were higher in group 2 than in other groups and lowest in group 1 and 5, whereas anti-inflammatory markers showed reversed changes in group 1 and other groups (all p < 0.05). The number of aquaporin-4+ and glial fibrillary acid protein+ stained cells were higher in group 2 as compared to other groups and lowest in groups 1 and 5 (all p < 0.01).

Conclusion

combined treatment with CsA and EPO was superior to either one alone in protecting rat brain from ischemic damage after IS.
Synthesis and characterization of aligned ZnO/BeO core/shell nanocable arrays on glass substrate
Authors: Zhou Minjie , Yi Zao , Li Kai , Zhang Jicheng , Wu Weidong
Published: August 2011

By sequential hydrothermal growth of ZnO nanowire arrays and thermal evaporation of Be, large-scale vertically aligned ZnO/BeO core/shell nanocable arrays on glass substrate have been successfully synthesized without further heat treatment. Detailed characterizations on the sample morphologies, compositions, and microstructures were systematically carried out, which results disclose the growth behaviors of the ZnO/BeO nanocable. Furthermore, incorporation of BeO shell onto ZnO core resulted in distinct improvement of optical properties of ZnO nanowire, i.e., significant enhancement of near band edge (NBE) emission as well as effective suppression of defects emission in ZnO. In particular, the NBE emission of nanocable sample shows a noticeable blue-shift compared with that of pristine ZnO nanowire, which characteristics most likely originate from Be alloying into ZnO. Consequently, the integration of ZnO and BeO into nanoscale heterostructure could bring up new opportunities in developing ZnO-based device for application in deep ultraviolet region.

PACS

61.46.K; 78.67.Uh; 81.07.Gf.
Ensemble Encoding of Nociceptive Stimulus Intensity in the Rat Medial and Lateral Pain Systems
Authors: Zhang Yang , Wang Ning , Wang Jin-Yan , Chang Jing-Yu , Woodward Donald J , Luo Fei
Published: August 2011

Background:

The ability to encode noxious stimulus intensity is essential for the neural processing of pain perception. It is well accepted that the intensity information is transmitted within both sensory and affective pathways. However, it remains unclear what the encoding patterns are in the thalamocortical brain regions, and whether the dual pain systems share similar responsibility in intensity coding.

Results:

Multichannel single-unit recordings were used to investigate the activity of individual neurons and neuronal ensembles in the rat brain following the application of noxious laser stimuli of increasing intensity to the hindpaw. Four brain regions were monitored, including two within the lateral sensory pain pathway, namely, the ventral posterior lateral thalamic nuclei and the primary somatosensory cortex, and two in the medial pathway, namely, the medial dorsal thalamic nuclei and the anterior cingulate cortex. Neuron number, firing rate, and ensemble spike count codings were examined in this study. Our results showed that the noxious laser stimulation evoked double-peak responses in all recorded brain regions. Significant correlations were found between the laser intensity and the number of responsive neurons, the firing rates, as well as the mass spike counts (MSCs). MSC coding was generally more efficient than the other two methods. Moreover, the coding capacities of neurons in the two pathways were comparable.

Conclusion:

This study demonstrated the collective contribution of medial and lateral pathway neurons to the noxious intensity coding. Additionally, we provide evidence that ensemble spike count may be the most reliable method for coding pain intensity in the brain.
Non-invasive interactive neurostimulation (InterX ™) reduces acute pain in patients following total knee replacement surgery: a randomised, controlled trial
Authors: Nigam Ashok K , Taylor Drena M , Valeyeva Zulia
Published: August 2011

Background

Adequate post-operative pain relief following total knee replacement (TKR) is very important to optimal post-operative recovery. Faster mobilisation and rehabilitation ultimately results in optimum recovery outcomes, but pain is often the limiting factor. This study evaluates the potential clinical benefit of the InterX neurostimulation device on pain reduction and rehabilitative outcome.

Methods

A clinical trial under the Hywel Dda Clinical Audit Committee to validate the clinical benefit of Non-invasive Interactive Neurostimulation (NIN) therapy using the InterX device was performed in patients undergoing TKR. 61 patients were randomised to treatment groups in blocks of two from the Theatre Operation List. The control group received the standard hospital course of pain medication and rehabilitation twice daily for 3 post-op days. The experimental group received 8 sessions of NIN therapy over 3 post-op days in addition to the standard course received by the Control group. Pain and range of motion were collected as the primary study measures.

Results

Sixty one subjects were enrolled and randomised, but 2 subjects (one/group) were excluded due to missing data at Baseline/Final; one subject in the InterX group was excluded due to pre-existing rheumatoid pain conditions confounding the analysis.

The experimental group pre- to post-session Verbal Rating Scale for pain (VRS) showed that NIN therapy consistently reduced the pain scores by a mean of 2.3 points (SE 0.11). The NIN pre-treatment score at Final was used for the primary ANCOVA comparison, demonstrating a significantly greater cumulative treatment effect of a mean 2.2 (SE 0.49) points pain reduction (p = 0.002). Control subjects only experienced a mean 0.34 (SE 0.49) point decrease in pain. Ninety degrees ROM was required to discharge the patient and this was attained as an average despite the greater Baseline deficit in the InterX group. Eight control patients and three experimental patients did not achieve this ROM.

Conclusions

The results clearly demonstrated the clinical benefit of NIN therapy as a supplement to the standard rehabilitation protocol. The subjects receiving InterX fared significantly better clinically. Within a relatively short 3-day period of time, patients in the experimental group obtained the necessary ROM for discharge and did it experiencing lower levels of pain than those in the control group.
Neurogenin2 regulates the initial axon guidance of cortical pyramidal neurons projecting medially to the corpus callosum
Authors: Hand Randal , Polleux Franck
Published: August 2011

Background

The formation of the mammalian central nervous system requires the establishment of complex neural circuits between a diverse array of neuronal subtypes. Here we report that the proneural transcription factor Neurogenin2 (Ngn2) is crucial for the proper specification of cortical axon projections.

Results

The genetic loss of Ngn2 in mice results in fewer callosal axons projecting towards the midline as well as abnormal midline crossing. shRNA-mediated knockdown of Ngn2 revealed its cell-autonomous requirement for the proper projection of axons from layer 2/3 pyramidal neurons to the midline in vivo. We found that the acute loss of Ngn2 in vivo induces the axon of superficial layer 2/3 neurons to project laterally towards aberrant cortical and subcortical targets.

Conclusions

These and previous results demonstrate that Ngn2 is required for the coordinated specification of cardinal features defining the phenotype of cortical pyramidal neurons, including their migration properties, dendritic morphology and axonal projection.
Inflammatory pseudotumor of the kidney: a case report
Authors: Khallouk Abdelhak , Ahallal Youness , Tazi Mohammed Fadl , Elfatemi Hinde , Tazi Elmehdi , Elammari Jalaleddine , Elfassi Mohammed Jamal , Farih Moulay Hassan
Published: August 2011

Introduction

Inflammatory pseudotumors, also known as inflammatory myofibroblastic tumors, are uncommon benign tumors of unknown etiology which may develop at several anatomical sites. In the urogenital tract, inflammatory pseudotumor usually affects the urinary bladder or the prostate. Inflammatory pseudotumor of the kidney is very rare. It is considered as a reactive inflammatory lesion that features very good prognosis.

Case presentation

We present the case of a 57-year-old Moroccan man who presented with a two-month history of gross hematuria and left lumbar pain. Imaging investigations revealed a left kidney mass and pathological examination of the nephrectomy specimen showed an inflammatory pseudotumor.

Conclusion

As the preoperative definitive diagnosis of such a tumor is not possible, surgery is advised because only pathological examination of the nephrectomy specimen can establish the diagnosis with certainty. From one case report and literature review, the authors suggest a diagnostic and therapeutic strategy for the management of this rare tumor.
Simultaneous utilization of glucose and xylose for lipid production by Trichosporon cutaneum
Authors: Hu Cuimin , Wu Siguo , Wang Qian , Jin Guojie , Shen Hongwei , Zhao Zongbao K
Published: August 2011

Background

Biochemical conversion of lignocellulose hydrolysates remains challenging, largely because most microbial processes have markedly reduced efficiency in the presence of both hexoses and pentoses. Thus, identification of microorganisms capable of efficient and simultaneous utilization of both glucose and xylose is pivotal to improving this process.

Results

In this study, we found that the oleaginous yeast strain Trichosporon cutaneum AS 2.571 assimilated glucose and xylose simultaneously, and accumulated intracellular lipid up to 59 wt% with a lipid coefficient up to 0.17 g/g sugar, upon cultivation on a 2:1 glucose/xylose mixture in a 3-liter stirred-tank bioreactor. In addition, no classic pattern of diauxic growth behavior was seen; the microbial cell mass increased during the whole culture process without any lag periods. In shake-flask cultures with different initial glucose:xylose ratios, glucose and xylose were consumed simultaneously at rates roughly proportional to their individual concentrations in the medium, leading to complete utilization of both sugars at the same time. Simultaneous utilization of glucose and xylose was also seen during fermentation of corn-stover hydrolysate with a lipid content and coefficient of 39.2% and 0.15 g/g sugar, respectively. The lipid produced had a fatty-acid compositional profile similar to those of conventional vegetable oil, indicating that it could have potential as a raw material for biodiesel production.

Conclusion

Efficient lipid production with simultaneous consumption of glucose and xylose was achieved in this study. This process provides an exciting opportunity to transform lignocellulosic materials into biofuel molecules, and should also encourage further study to elucidate this unique sugar-assimilation mechanism.
Toxoplasma gondii infection in humans in China
Authors: Zhou Peng , Chen Zhaoguo , Li Hai-Long , Zheng Haihong , He Shenyi , Lin Rui-Qing , Zhu Xing-Quan
Published: August 2011

Toxoplasmosis is a zoonotic infection of humans and animals, caused by the opportunistic protozoan Toxoplasma gondii, a parasite belonging to the phylum Apicomplexa. Infection in pregnant women may lead to abortion, stillbirth or other serious consequences in newborns. Infection in immunocompromised patients can be fatal if not treated. On average, one third of people are chronically infected worldwide. Although very limited information from China has been published in the English journals, T. gondii infection is actually a significant human health problem in China. In the present article, we reviewed the clinical features, transmission, prevalence of T. gondii infection in humans in China, and summarized genetic characterizations of reported T. gondii isolates. Educating the public about the risks associated with unhealthy food and life style habits, tracking serological examinations to special populations, and measures to strengthen food and occupational safety are discussed.
The Inflammasome and Caspase-1 Activation: A New Mechanism Underlying Increased Inflammatory Activity in Human Visceral Adipose Tissue
Authors: Koenen Tim B. , Stienstra Rinke , van Tits Lambertus J. , Joosten Leo A. B. , van Velzen Jeroen F. , Hijmans Anneke , Pol Jillis A. , van der Vliet J. A. , Netea Mihai G. , Tack Cees J. , Stalenhoef Anton F. H. , de Graaf Jacqueline
Published: August 2011

The immune competent abdominal adipose tissue, either stored viscerally [visceral adipose tissue (VAT)] or sc [sc adipose tissue (SAT)], has been identified as a source of IL-1β and IL-18. To become active, the proforms of these cytokines require processing by caspase-1, which itself is mediated by the inflammasome. In this descriptive study, we investigate the expression of inflammasome components and caspase-1 in human fat and determine whether caspase-1 activity contributes to the enhanced inflammatory status of VAT. Paired SAT and VAT biopsies from 10 overweight subjects (body mass index, 25–28 kg/m2) were used to study the cellular composition and the intrinsic inflammatory capacity of both adipose tissue depots. The percentage of CD8+ T cells within the lymphocyte fraction was significantly higher in VAT compared with SAT (41.6 vs. 30.4%; P < 0.05). Adipose tissue cultures showed a higher release of IL-1β (10-fold; P < 0.05), IL-18 (3-fold; P < 0.05), and IL-6 and IL-8 (3-fold, P < 0.05; and 4-fold, P < 0.05, respectively) from VAT compared with SAT that was significantly reduced by inhibiting caspase-1 activity. In addition, caspase-1 activity was 3-fold (P < 0.05) higher in VAT compared with SAT, together with an increase in the protein levels of the inflammasome members apoptosis-associated speck-like protein containing a C-terminal caspase-recruitment domain (2-fold; P < 0.05) and nucleotide-binding oligomerization domain- like receptor pyrin domain containing 3 (2-fold; nonsignificant). Finally, caspase-1 activity levels were positively correlated with the percentage of CD8+ T cells present in adipose tissue. Our results show that caspase-1 and nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 inflammasome members are abundantly present in human VAT. The increased intrinsic caspase-1 activity in VAT represents a novel and specific inflammatory pathway that may determine the proinflammatory character of this specific depot.
The E3 Ubiquitin Ligase Mahogunin Ubiquitinates the Melanocortin 2 Receptor
Authors: Cooray Sadani N. , Guasti Leonardo , Clark Adrian J. L.
Published: August 2011

Mahogunin ring fnger-1(MGRN1) encodes an E3 ubiquitin ligase and is mutated in the mahoganoid mouse. The mahoganoid mouse mutant shows similarities to the phenotype of another spontaneous mouse mutation known as mahogunin (mutation in attractin) presenting with dark coat color, spongiform neurodegeneration, and high embryonic lethality. It has long been hypothesized that MGRN1 may down-regulate the function of the melanocortin 1 receptor (MC1R) via ubiquitination or internalization because it has been shown to possess E3 ubiquitin ligase activity. However, a recent study revealed that MGRN1's role in MC1R function was independent of receptor ubiquitination and that MGRN1 negatively regulated MC1R function by competing with Gαs for receptor binding. In this study we attempted to determine whether MGRN1 is involved in the function of the melanocortin 2 receptor (MC2R). We show that MGRN1 is expressed in the zona glomerulosa and fasciculata cells of the adrenal cortex, and in transfected human embryonic kidney 293 cells it colocalizes at the cell surface with the MC2R, and coimmunoprecipitates with the MC2R. However MGRN1 did not appear to influence the cAMP-signaling function of the MC2R. In the presence of MGRN1 the MC2R is ubiquitinated and, after ACTH stimulation, evidence of multi-monoubiquitination appears. It therefore seems probable that the role of MGRN1 in the adrenal relates to the trafficking and/or degradation of the MC2R.
Repressor of Estrogen Receptor Activity (REA) Is Essential for Mammary Gland Morphogenesis and Functional Activities: Studies in Conditional Knockout Mice
Authors: Park Sunghee , Zhao Yuechao , Yoon Sangyeon , Xu Jianming , Liao Lan , Lydon John , DeMayo Franco , O'Malley Bert W. , Katzenellenbogen Benita S.
Published: August 2011

Estrogen receptor (ER) is a key regulator of mammary gland development and is also implicated in breast tumorigenesis. Because ER-mediated activities depend critically on coregulator partner proteins, we have investigated the consequences of reduction or loss of function of the coregulator repressor of ER activity (REA) by conditionally deleting one allele or both alleles of the REA gene at different stages of mammary gland development. Notably, we find that heterozygosity and nullizygosity for REA result in very different mammary phenotypes and that REA has essential roles in the distinct morphogenesis and functions of the mammary gland at different stages of development, pregnancy, and lactation. During puberty, mice homozygous null for REA in the mammary gland (REAf/f PRcre/+) showed severely impaired mammary ductal elongation and morphogenesis, whereas mice heterozygous for REA (REAf/+ PRcre/+) displayed accelerated mammary ductal elongation, increased numbers of terminal end buds, and up-regulation of amphiregulin, the major paracrine mediator of estrogen-induced ductal morphogenesis. During pregnancy and lactation, mice with homozygous REA gene deletion in mammary epithelium (REAf/f whey acidic protein-Cre) showed a loss of lobuloalveolar structures and increased apoptosis of mammary alveolar epithelium, leading to impaired milk production and significant reduction in growth of their offspring, whereas body weights of the offspring nursed by females heterozygous for REA were slightly greater than those of control mice. Our findings reveal that REA is essential for mammary gland development and has a gene dosage-dependent role in the regulation of stage-specific physiological functions of the mammary gland.
The Ca2+/Calmodulin-Dependent Protein Kinase Kinase, CaMKK2, Inhibits Preadipocyte Differentiation
Authors: Lin Fumin , Ribar Thomas J. , Means Anthony R.
Published: August 2011

When fed a standard chow diet, CaMKK2 null mice have increased adiposity and larger adipocytes than do wild-type mice, whereas energy balance is unchanged. Here, we show that Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is expressed in preadipocytes, where it functions as an AMP-activated protein kinase (AMPK)α kinase. Acute inhibition or deletion of CaMKK2 in preadipocytes enhances their differentiation into mature adipocytes, which can be reversed by 5-aminoimidazole-4-carboxamide ribonucleotide-mediated activation of AMPK. During adipogenesis, CaMKK2 expression is markedly decreased and temporally accompanied by increases in mRNA encoding the early adipogenic genes CCAAT/enhancer binding protein (C/EBP) β and C/EBP δ. Preadipocyte factor 1 has been reported to inhibit adipogenesis by up-regulating sex determining region Y-box 9 (Sox9) expression in preadipocytes and Sox9 suppresses C/EBPβ and C/EBPδ transcription. We show that inhibition of the CaMKK2/AMPK signaling cascade in preadipocytes reduces preadipocyte factor 1 and Sox9 mRNA resulting in accelerated adipogenesis. We conclude that CaMKK2 and AMPK function in a signaling pathway that participates in the regulation of adiposity.
Insulin/IGF-I Regulation of Necdin and Brown Adipocyte Differentiation Via CREB- and FoxO1-Associated Pathways
Authors: Cypess Aaron M. , Zhang Hongbin , Schulz Tim J. , Huang Tian Lian , Espinoza Daniel O. , Kristiansen Karsten , Unterman Terry G. , Tseng Yu-Hua
Published: August 2011

Brown adipose tissue plays an important role in obesity, insulin resistance, and diabetes. We have previously shown that the transition from brown preadipocytes to mature adipocytes is mediated in part by insulin receptor substrate (IRS)-1 and the cell cycle regulator protein necdin. In this study, we used pharmacological inhibitors and adenoviral dominant negative constructs to demonstrate that this transition involves IRS-1 activation of Ras and ERK1/2, resulting in phosphorylation of cAMP response element-binding protein (CREB) and suppression of necdin expression. This signaling did not include an elevation of intracellular calcium. A constitutively active form of CREB expressed in IRS-1 knockout cells decreased necdin promoter activity, necdin mRNA, and necdin protein levels, leading to a partial restoration of differentiation. By contrast, forkhead box protein (Fox)O1, which is regulated by the phosphoinositide 3 kinase-Akt pathway, increased necdin promoter activity. Based on reporter gene assays using truncations of the necdin promoter and chromatin immunoprecipitation studies, we demonstrated that CREB and FoxO1 are recruited to the necdin promoter, likely interacting with specific consensus sequences in the proximal region. Based on these results, we propose that insulin/IGF-I act through IRS-1 phosphorylation to stimulate differentiation of brown preadipocytes via two complementary pathways: 1) the Ras-ERK1/2 pathway to activate CREB and 2) the phosphoinositide 3 kinase-Akt pathway to deactivate FoxO1. These two pathways combine to decrease necdin levels and permit the clonal expansion and coordinated gene expression necessary to complete brown adipocyte differentiation.
Characterization of Novel RFamide Peptides in the Central Nervous System of the Brown Hagfish: Isolation, Localization, and Functional Analysis
Authors: Osugi Tomohiro , Uchida Katsuhisa , Nozaki Masumi , Tsutsui Kazuyoshi
Published: August 2011

RFamide (RFa) peptides play various important roles in the central nervous system in both invertebrates and vertebrates. However, there is no evidence of the existence of any RFamide peptide in the brain of hagfish, one of the oldest lineages of vertebrates. In this study, we sought to identify novel RFamide peptides from the brains of hagfish (Paramyxine atami). We identified four novel RFamide peptides, which had the C-terminal Pro-Gln-Arg-Phe-NH2 structure. cDNA cloning revealed that the identified RFamide peptides are encoded in two types of cDNA. Molecular phylogenetic analysis of the two precursors indicated that the hagfish RFamide peptides belong to the PQRFamide peptide group that includes mammalian neuropeptide FF and AF. Based on immunohistochemistry and in situ hybridization, hagfish PQRFamide peptide precursor mRNA and its translated peptides were localized in the infundibular nucleus of the hypothalamus. Immunoreactive fibers were terminated on blood vessels in the infundibular nucleus. Dense immunoreactive fibers were also observed in other brain regions. We further showed that one of the hagfish PQRFamide peptides significantly stimulated the expression of gonadotropin-β mRNA in the cultured hagfish pituitary. These results indicate that the control mechanism of gonadotropin expression by a hypothalamic neuropeptide evolved in the agnathan brain. This is the first evidence describing the identification of RFamide peptides in the hagfish brain. This is also the first report showing the regulation of gonadotropin expression by a homolog of neuropeptide FF that belongs to the PQRFamide peptide group in any vertebrate.
Minireview: Nesfatin-1—An Emerging New Player in the Brain-Gut, Endocrine, and Metabolic Axis
Authors: Stengel Andreas , Taché Yvette
Published: August 2011

Nesfatin-1 is a recently identified 82-amino-acid peptide derived from the precursor protein, nucleobindin2 (NUCB2). The brain distribution of NUCB2/nesfatin-1 at the mRNA and protein level along with functional studies in rodents support a role for NUCB2/nesfatin-1 as a novel satiety molecule acting through leptin-independent mechanisms. In addition, nesfatin-1 induces a wide spectrum of central actions to stimulate the pituitary-adrenal axis and sympathetic nervous system and influences visceral functions and emotion. These central actions combined with the activation of NUCB2/nesfatin-1 neurons in the brain by various stressors are indicative of a role in the adaptive response under stressful conditions. In the periphery, evidence is mounting that nesfatin-1 exerts a direct glucose-dependent insulinotropic action on β-cells of the pancreatic islets. However, the cellular mechanisms of nesfatin-1's action remain poorly understood, partly because the receptor through which nesfatin-1 exerts its pleiotropic actions is yet to be identified.
Regulation of gas exchange and haemolymph pH in the cockroach Nauphoeta cinerea
Authors: Matthews Philip G. D. , White Craig R.
Published: August 2011

Ventilatory control of internal CO2 plays an important role in regulating extracellular acid–base balance in terrestrial animals. While this phenomenon is well understood among vertebrates, the role that respiration plays in the acid–base balance of insects is in need of much further study. To measure changes in insect haemolymph pH, we implanted micro pH optodes into the haemocoel of cockroaches (Nauphoeta cinerea). They were then exposed to normoxic, hypoxic, hyperoxic and hypercapnic atmospheres while their haemolymph pH, and abdominal ventilation frequency were measured simultaneously. Intratracheal O2 levels were also measured in separate experiments. It was found that cockroaches breathing continuously control their ventilation to defend a haemolymph pH of 7.3, except under conditions where hypoxia (<10% O2) induces hyperventilation, or where ambient hypercapnia is in excess of haemolymph (>1% CO2). In contrast, intratracheal O2 levels fluctuated widely, but on average remained above 15% in normoxic (21% O2) atmospheres. Decapitation caused the cockroaches to display discontinuous gas exchange cycles (DGCs). The alternating periods of ventilation and apnoea during DGCs caused haemolymph pH to fluctuate by 0.11 units. Exposure to hypoxia caused haemolymph pH to increase and initiated brief bouts of spiracular opening prior to the active ventilation phase. The spontaneous occurrence of DGCs in decapitated cockroaches indicates that central pattern generators in the thoracic and abdominal ganglia generate the periodic gas exchange pattern in the absence of control from the cephalic ganglion. This pattern continues to maintain gas exchange, but with less precision.
Behavioural and kinematic components of the fast-start escape response in fish: individual variation and temporal repeatability
Authors: Marras Stefano , Killen Shaun S. , Claireaux Guy , Domenici Paolo , McKenzie David J.
Published: August 2011

Inter-individual variation in physiological performance traits, which is stable over time, can be of potential ecological and evolutionary significance. The fish escape response is interesting in this regard because it is a performance trait for which inter-individual variation may determine individual survival. The temporal stability of such variation is, however, largely unexplored. We quantified individual variation of various components of the escape response in a population of European sea bass (Dicentrarchus labrax), considering both non-locomotor (responsiveness and latency) and locomotor (speed, acceleration, turning rate, turning angle and distance travelled in a fixed time, Desc) variables. We assessed whether variation in performance was temporally stable and we searched for any trade-offs among the components of the response that might explain why the variation persisted in the population. The coefficient of variation was high for all components, from 23% for turning rate to 41% for Desc, highlighting the non-stereotypic nature of the response. Individual performance for all variables was significantly repeatable over five sequential responses at 30 min intervals, and also repeatable after a 30 day interval for most of the components. This indicates that the variation is intrinsic to the individuals, but there was no evidence for trade-offs amongst the components of the response, suggesting that, if trade-offs exist, they must be against other ecologically important behavioural or performance traits.