Kinetic analysis of human metallothionein and CdTe quantum dot complexes using fluorescence and voltammetry techniques.

Kinetic analysis of human metallothionein and CdTe quantum dot complexes using fluorescence and voltammetry techniques.

Colloids Surf B Biointerfaces. 2017 Sep 14;160:381-389

Authors: Guszpit E, Krejčová L, Křížková S, Kepinska M, Richtera L, Kopel P, Adam V, Milnerowicz H

Abstract
Thanks to quantum dots' (QDs) properties, they can be used as selective and sensitive biomarkers in molecular imaging. In a previous paper, we confirmed the possibility of interaction between mercaptosuccinic acid-capped cadmium telluride QDs (MSA-CdTe) and human metallothionein (MT). The aim of this study was to expand on our previous research with an evaluation of the stability of the formed complexes between human MT and four CdTe compounds of the following sizes: 3.4nm (blue QDs), 3.8nm (green QDs), 4.5nm (yellow QDs), and 5.2nm (red QDs). Complexes were evaluated over time using fluorescence intensity and differential pulse voltammetry. Differences between the voltammograms obtained for standard solutions and for CdTe+MT show that complexes were formed. An increase in fluorescence intensity was observed for blue (Δ%≈40 for t=1→120min) and red (Δ%≈30 for t=1→120min) CdTe-MT complexes than CdTe alone, whereas green and yellow CdTe-MT complexes had a lower fluorescence intensity than CdTe alone. A stronger time dependence of the mercaptosuccinic acid (MSA) peak height on the timeline and differences in the MSA peak shape (in CdTe, and CdTe+MT complexes) were also observed by voltammetry. Authors noticed a decrease in the Cat2 signal of the red and green CdTe+MT complexes at the time of conjugation. Our results reveal that the size of QDs has an impact on the interaction between CdTe and human MT, as well as on the stability of complexes formed during these interactions. The bioconjugates' stability was also found to depend on the time of interaction.

PMID: 28963959 [PubMed - as supplied by publisher]

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Diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation: a systematic review and meta-analysis.

Diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation: a systematic review and meta-analysis.

Acta Obstet Gynecol Scand. 2017 Sep 30;:

Authors: Pagani G, Cali G, Acharya G, Timor Trisch I, Palacios-Jaraquemada J, Familiari A, Buca D, Manzoli L, Flacco ME, Fanfani F, Liberati M, Scambia G, D'Antonio F

Abstract
INTRODUCTION: Our objective was to elucidate the overall diagnostic accuracy of ultrasound in detecting the severity of abnormally invasive placentation (AIP).
MATERIAL AND METHODS: Medline, Embase, CINAHL and The Cochrane databases were searched. The ultrasound signs explored were: loss of hypoechoic (clear) zone in the placental-uterine interface, placental lacunae, bladder wall interruption, myometrial thinning, focal exophitic mass, placental lacunar flow, sub-placental vascularity, and uterovescical hypervascularity.
RESULTS: Twenty studies (3209 pregnancies) were included. Ultrasound had an overall good diagnostic accuracy in identifying the depth of placental invasion with a sensitivity of 90.6%, 93.0%, 89.5% and 81.2% for placenta accreta, increta, accreta/increta and percreta respectively; the corresponding figures for specificity were 97.1%, 98.4%, 94.7%, 98.9%. Placental lacunae had a sensitivity of 74.8%, 88.6% and 76.3% for the detection of placenta accreta, increta and percreta respectively. Sensitivity and specificity of loss of the clear zone in identifying placenta accreta were 74.9% and 92.0%, while the corresponding figures for placenta increta and percreta were 91.6% and 76.9% and 88.1% and 71.1%. Lacunar flow had a sensitivity of 81.2%, 84.3% and 45.2% for the detection of placenta accreta, increta and percreta respectively; the corresponding figures for specificity were 84.0%, 79.7% and 75.3%. Sensitivity of uterovescical hypervascularity was low for the detection of placenta accreta (12.3%) while it was high for placenta increta (94.4%) and percreta (86.2%); the corresponding figures for specificity were 90.8%, 88.0% and 88.2% respectively.
CONCLUSIONS: Ultrasound has an overall good diagnostic accuracy in recognizing the depth and the topography of placental invasion. This article is protected by copyright. All rights reserved.

PMID: 28963728 [PubMed - as supplied by publisher]

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Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo.

Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo.

Sci Rep. 2017 Sep 29;7(1):12412

Authors: Llavero Hurtado M, Fuller HR, Wong AMS, Eaton SL, Gillingwater TH, Pennetta G, Cooper JD, Wishart TM

Abstract
Synapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3 (-/-) mouse model of a juvenile form of NCL. We profiled and compared the molecular composition of anatomically-distinct, differentially-affected pre-synaptic populations from the Cln3 (-/-) mouse brain using proteomics followed by bioinformatic analyses. Identified protein candidates were then tested using a Drosophila CLN3 model to study their ability to modify the CLN3-neurodegenerative phenotype in vivo. We identified differential perturbations in a range of molecular cascades correlating with synaptic vulnerability, including valine catabolism and rho signalling pathways. Genetic and pharmacological targeting of key 'hub' proteins in such pathways was sufficient to modulate phenotypic presentation in a Drosophila CLN3 model. We propose that such a workflow provides a target rich method for the identification of novel disease regulators which could be applicable to the study of other conditions where appropriate models exist.

PMID: 28963550 [PubMed - in process]

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Preferential sensing and response to microenvironment stiffness of human dermal fibroblast cultured on protein micropatterns fabricated by 3D multiphoton biofabrication.

Preferential sensing and response to microenvironment stiffness of human dermal fibroblast cultured on protein micropatterns fabricated by 3D multiphoton biofabrication.

Sci Rep. 2017 Sep 29;7(1):12402

Authors: Tong MH, Huang N, Ngan AHW, Du Y, Chan BP

Abstract
While cells are known to sense and respond to their niche including the matrix and the mechanical microenvironment, whether they preferentially sense and react to the stiffness of their microenvironment regardless of its intrinsic material properties is unknown. In this work, protein micropillar arrays with independently controllable stiffness via alterations in pillar height and elastic modulus via laser power used during photochemical cross-linking, were fabricated using a recently developed multiphoton-based 3D protein micro-patterning technology. Human dermal fibroblasts were cultured on these micropillar arrays and the specific interactions between cells and the protein micropatterns particularly on the formation and maturation of the cell-matrix adhesions, were investigated via immunofluorescence staining of the major molecular markers of the adhesions and the measurement of their cluster size, respectively. Our results showed that the cluster size of focal adhesions increased as the stiffness of the micropillar arrays increased, but it was insensitive to the elastic modulus of the protein micropillars that is one of the intrinsic material properties. This finding provides evidence to the notion that cells preferentially sense and react to the stiffness, but not the elastic modulus of their microenvironment.

PMID: 28963517 [PubMed - in process]

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Evaluation of irreversible protein thermal inactivation caused by breakage of disulphide bonds using methanethiosulphonate.

Evaluation of irreversible protein thermal inactivation caused by breakage of disulphide bonds using methanethiosulphonate.

Sci Rep. 2017 Sep 29;7(1):12471

Authors: Futami J, Miyamoto A, Hagimoto A, Suzuki S, Futami M, Tada H

Abstract
Many extracellular globular proteins have evolved to possess disulphide bonds in their native conformations, which aids in thermodynamic stabilisation. However, disulphide bond breakage by heating leads to irreversible protein denaturation through disulphide-thiol exchange reactions. In this study, we demonstrate that methanethiosulphonate (MTS) specifically suppresses the heat-induced disulphide-thiol exchange reaction, thus improving the heat-resistance of proteins. In the presence of MTS, small globular proteins that contain disulphides can spontaneously refold from heat-denatured states, maintaining wild-type disulphide pairing. Because the disulphide-thiol exchange reaction is triggered by the generation of catalytic amounts of perthiol or thiol, rapid and specific perthiol/thiol protection by MTS reagents prevents irreversible denaturation. Combining MTS reagents with another additive that suppresses chemical modifications, glycinamide, further enhanced protein stabilisation. In the presence of these additives, reliable remnant activities were observed even after autoclaving. However, immunoglobulin G and biotin-binding protein, which are both composed of tetrameric quaternary structures, failed to refold from heat-denatured states, presumably due to chaperon requirements. Elucidation of the chemical modifications involved in irreversible thermoinactivation is useful for the development of preservation buffers with optimum constitutions for specific proteins. In addition, the impact of disulphide bond breakage on the thermoinactivation of proteins can be evaluated using MTS reagents.

PMID: 28963503 [PubMed - in process]

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Student nurses experience of a "fairy garden" healing haven garden for sick children.

Student nurses experience of a "fairy garden" healing haven garden for sick children.

Nurse Educ Today. 2017 Sep 14;59:88-93

Authors: van der Riet P, Jitsacorn C, Junlapeeya P, Thursby P

Abstract
BACKGROUND: The concept and philosophy of healing environments in health care is not new and there has been recent research into the experience of nurses and families experience of healing environments producing positive outcomes in relieving stress and improving quality of life. However, there is little in-depth information about student nurse's experience of healing environments in support of patients.
AIM: To report on the stories of student nurses who participated in formal and informal activities in a healing haven environment called a Fairy Garden (FG) within a hospital in northern Thailand. Their beliefs about the care of sick children in an environment designed to provide educational and recreational activity during hospital care are explored.
METHODS: Narrative inquiry, a qualitative methodology was selected to capture the main threads of the participants' experience. Clandinin's narrative inquiry framework involving the three commonality dimensions of sociality, temporality and place were used in analysing the data. Sixty-two student nurses from a Thai College of Nursing and from an Australian university were interviewed.
RESULTS: In this study the place of a FG has been investigated as a non-clinical environment providing sick children with exposure to nature, play activities and spaces to explore. Findings include three main threads: freedom to be a child not a sick child, engaging in care and professionalism, a moment in time of living fantasy.
CONCLUSIONS: Student nurses in this study had a broader understanding of health care other than the biomedical model. It transformed their learning and opened their eyes to a more holistic approach to humanising care of sick children.

PMID: 28963920 [PubMed - as supplied by publisher]

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Bodies of children in the Institute of Anatomy in Halle (Saale), Germany, between 1920 and 1945.

Bodies of children in the Institute of Anatomy in Halle (Saale), Germany, between 1920 and 1945.

Ann Anat. 2017 Sep 26;:

Authors: Winter F, Stoevesandt D, Schultka R, Viebig M, Moeller K, Steger F, Kielstein H

Abstract
At the Institute of Anatomy and Cell Biology in Halle (Saale) 74 children's bodies of unknown historical provenance are being held in storage. The aim of this study was the evaluation of their identities, the circumstances of their acquisition, as well as the documentation of their individual characteristics. For these purposes, all bodies were comprehensively examined and photo-documented. Furthermore, CT-scans of 29 bodies were performed and information was collected from various local and national archives. Although most of the bodies were found to be those of stillborn children and infants, five children were between two and twelve years old, according to an age estimate by body-length and carpal bone analysis. The CT-scans revealed the cause of death for some of the children. The embalming method indicates that the bodies date from the first decades of the 20th century, and archival sources containing documents from 1920 to 1960 strongly suggest that these children's bodies were acquired by Institute of Anatomy between 1920 and 1942. During that period, a total of 2,602 children's bodies were delivered to the Institute of Anatomy and registered in the communal burial records. At this point, there is no evidence that these children might have been victims of National Socialist crimes. It is planned to give them a dignified burial.

PMID: 28963045 [PubMed - as supplied by publisher]

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Epoetin Alfa: A Cause of Coronary Artery Thrombosis

Introduction. Epoetin alfa is an erythrocyte-stimulating factor. We here present a case of an anemic patient, who was given epogen before a coronary artery bypass (CABG) surgery and developed periprocedural myocardial infarction. To our knowledge, there has been no previous case reported of epogen causing myocardial infarction. Case Presentation. 66-year-old female presented with substernal chest pain. EKG showed ST segment elevations in aVf and L-III. Patient underwent left heart catheterization (LHC) and had triple vessel disease. A bare metal stent was placed in RCA. Patient continued to have symptoms after discharge and presented to the ED again with these complaints. She underwent coronary artery bypass surgery (CABG). Before the procedure, patient's hemoglobin was 11.1 grams/deciliter and was given epogen to raise hemoglobin level. Postoperative day (POD) #1 patient had ST elevations in inferior and anterolateral leads. She was diagnosed with periprocedural myocardial infarction. Patient underwent repeat LHC, which identified obstruction of saphenous vein graft (SVG). Hypercoagulable workup was negative for any disease and the patient was diagnosed with epogen induced early graft occlusion. Conclusion. Epogen administration can cause myocardial infarction and coronary artery thrombosis. We suggest that physicians use epogen very cautiously, especially in population who has underlying coronary artery disease.

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Exploration of Superior Modality: Safety and Efficacy of Hypofractioned Image-Guided Intensity Modulated Radiation Therapy in Patients with Unresectable but Confined Intrahepatic Hepatocellular Carcinoma

Purpose. To evaluate the efficacy and safety of hypofractioned image-guided intensity modulated radiation therapy (IG-IMRT) for unresectable but confined intrahepatic hepatocellular carcinoma in comparison with conventional 3-dimensional conformal radiotherapy (3D-CRT). Methods. Ninety patients with unresectable but confined intrahepatic hepatocellular carcinoma without distant metastasis and tumor thrombosis received external beam radiation therapy. Of these patients, 45 received IG-IMRT and 45 received 3D-CRT. The IG-IMRT design delivered a median total hypofractionated dose of 54 Gy (2.2–5.5 Gy/fx), and 3D-CRT delivered a median total dose of 54 Gy with a conventional fraction (2.0 Gy/fx). The clinical response, overall survival, and side effects were analyzed. Results. The IG-IMRT group showed significantly higher 1-year survival (93.3 versus 77.8%) and 2-year survival (73.3 versus 51.1%) and longer median survival (44.7 versus 24.0 months) than the 3D-CRT group. Multivariate analysis indicated that the patients with intrahepatic tumors smaller than 8 cm, prior TACE before RT, and IG-IMRT would have a survival benefit. There were no significant differences in the rates of side effects between the two groups. Conclusion. Hypofractioned IG-IMRT could improve the therapeutic response and confer a potential survival of patients with unresectable but confined intrahepatic hepatocellular carcinoma compared to 3D-CRT with acceptable toxicity.

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XBP1-Mediated BiP/GRP78 Upregulation Copes with Oxidative Stress in Mosquito Cells during Dengue 2 Virus Infection

Dengue viruses (DENVs) cause dengue fever which is an important mosquito-borne disease in tropical areas. Generally, DENV does not cause cellular damage in mosquito cells. However, alterations in cytosolic calcium ions ([Ca2+]cyt) and the mitochondrial membrane potential (MMP), as well as accumulated reactive oxygen species (ROS), including superoxide anions () and hydrogen peroxide (H2O2), can be detected in C6/36 cells with DENV2 infection. Evident upregulation of BiP/GRP78 also appeared at 24 h postinfection in DENV2-infected C6/36 cells. As expression of BiP/GRP78 mRNA was reduced when the transcription factor X-box-binding protein-1 (XBP1) was knocked down in C6/36 cells, it demonstrated that BiP/GRP78 is the target gene regulated by the XBP1 signal pathway. We further demonstrated that the expression and splicing activity of XBP1 were upregulated in parallel with DENV2 infection in C6/36 cells. In C6/36 cells with BiP/GRP78 overexpression, oxidative stress indicators including [Ca2+]cyt, MMP, , and H2O2 were all pushed back to normal. Taken together, DENV2 activates XBP1 at earlier stage of infection, followed by upregulating BiP/GRP78 in mosquito cells. This regulatory pathway contributes a cascade in relation to oxidative stress alleviation. The finding provides insights into elucidating how mosquitoes can healthily serve as a vector of arboviruses in nature.

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Concise Neural Nonaffine Control of Air-Breathing Hypersonic Vehicles Subject to Parametric Uncertainties

In this paper, a novel simplified neural control strategy is proposed for the longitudinal dynamics of an air-breathing hypersonic vehicle (AHV) directly using nonaffine models instead of affine ones. For the velocity dynamics, an adaptive neural controller is devised based on a minimal-learning parameter (MLP) technique for the sake of decreasing computational loads. The altitude dynamics is rewritten as a pure feedback nonaffine formulation, for which a novel concise neural control approach is achieved without backstepping. The special contributions are that the control architecture is concise and the computational cost is low. Moreover, the exploited controller possesses good practicability since there is no need for affine models. The semiglobally uniformly ultimate boundedness of all the closed-loop system signals is guaranteed via Lyapunov stability theory. Finally, simulation results are presented to validate the effectiveness of the investigated control methodology in the presence of parametric uncertainties.

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Management of Head and Neck Burns-A 15-Year Review.

Management of Head and Neck Burns-A 15-Year Review.

J Oral Maxillofac Surg. 2017 Sep 11;:

Authors: Hamilton TJ, Patterson J, Williams RY, Ingram WL, Hodge JS, Abramowicz S

Abstract
PURPOSE: The purpose of this project was to characterize patients with isolated head and neck burns admitted to the Grady Memorial Hospital (GMH) Burn Center (Atlanta, GA).
MATERIALS AND METHODS: This was a retrospective case series of patients admitted to the GMH Burn Center with the primary diagnosis of head and neck burns from 2000 through 2015. Demographic data (gender and age) were recorded. Burn details (etiology, mechanism, percentage of burned total body surface area, depth, and associated injuries) were summarized. Patient management and hospital course were documented. Data were collected using a standardized collection form. Descriptive statistics were computed.
RESULTS: There were 5,938 patients admitted to burn unit at the GMH Burn Center during the study period. Of these, 2,547 patients had head and neck burns and 205 patients met the inclusion criteria. Most (n = 136; 66%) were male, with a mean age of 40 years. The most common burn depth was superficial partial thickness. Flame burns were the most likely mechanism related to full-thickness injury. Approximately one fourth of patients had an associated injury, such as inhalation or ocular injury. Surgical interventions consisted of tangential excision and split-thickness skin grafting, contracture release, excision of hypertrophic scars, and rotational flaps. Mean length of hospital stay for isolated head and neck burns was 4.4 days. Overall mortality was 2%.
CONCLUSION: The results of this study show that superficial partial-thickness head and neck burns are more likely to occur from accidental exposure to flames in men older than 55 years. Owing to an increase in risk and mortality of inhalation injury associated with head and neck burns, airway protection and respiratory management are critical considerations of head and neck burn management.

PMID: 28963867 [PubMed - as supplied by publisher]

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Chairside molecular imaging of aberrant glycosylation in subjects with suspicious oral lesions using fluorescently labeled wheat germ agglutinin.

Chairside molecular imaging of aberrant glycosylation in subjects with suspicious oral lesions using fluorescently labeled wheat germ agglutinin.

Head Neck. 2017 Sep 30;:

Authors: Baeten J, Johnson A, Sunny S, Suresh A, Birur P, Uma K, Kademani D

Abstract
BACKGROUND: Aberrant sialylation is accepted as a carcinogenic biomarker. In previous work, fluorescently labeled wheat germ agglutinin (WGA) distinguished between cancerous and normal oral biopsies. The purpose of this study was to investigate WGA-fluorescein isothiocyanate (FITC) as a point-of-care tool for detecting oral malignant and dysplastic lesions in vivo.
METHODS: Subject recruitment was divided into two groups: (1) the clinically normal oral mucosa group; or (2) the presence of clinically suspicious oral lesion(s) group. A WGA-FITC solution was topically applied to observable lesions or to half the subject's mouth (sagittal plane) if lesions were absent. Fluorescent molecular imaging was used to evaluate WGA-FITC localization.
RESULTS: Fluorescent imaging in 55 subjects demonstrated that WGA-FITC could detect histopathologically-confirmed cancerous and dysplastic lesions with high sensitivity (100% and 81%, respectively) and specificity (82%).
CONCLUSION: This study supports in vivo fluorescent molecular imaging of WGA-FITC to visualize aberrant sialic acid expression associated with carcinogenesis. This technique resulted in the immediate chairside detection of oral cancerous and dysplastic lesions.

PMID: 28963821 [PubMed - as supplied by publisher]

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Genomic profiling of intestinal-type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes.

Genomic profiling of intestinal-type sinonasal adenocarcinoma reveals subgroups of patients with distinct clinical outcomes.

Head Neck. 2017 Sep 30;:

Authors: López-Hernández A, Pérez-Escuredo J, Vivanco B, García-Inclán C, Potes-Ares S, Cabal VN, Riobello C, Costales M, López F, Llorente JL, Hermsen MA

Abstract
BACKGROUND: Patients with intestinal-type sinonasal adenocarcinoma (ITAC) have an unfavorable prognosis and new therapeutic approaches are needed to improve clinical management.
METHODS: Genetic analysis of 96 ITACs was performed by microarray comparative genomic hybridization and immunohistochemistry and correlated to previously obtained mutation, methylation, and protein expression data, and with pathological characteristics and clinical outcome.
RESULTS: Seven copy number alterations (CNAs) were significantly associated with unfavorable clinical outcome: gains at 1q22-23, 3q28-29, 6p22, and 13q31-33, and losses at 4p15-16, 4q32-35, and 10q24. Unsupervised cluster analysis resulted in 5 subgroups of ITAC with significantly distinct genetic signatures and clinical outcomes, independently of disease stage or histological subtype.
CONCLUSION: These data may guide studies to identify driver genes and signaling pathways involved in ITAC. In addition, the subclassification of genetic subgroups of patients with distinct clinical behavior can aid therapeutic decision making and may ultimately lead to personalized therapy with targeted inhibitors.

PMID: 28963820 [PubMed - as supplied by publisher]

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Serum parathyroid hormone and alkaline phosphatase as predictors of calcium requirements after total parathyroidectomy for hypocalcemia in secondary hyperparathyroidism.

Serum parathyroid hormone and alkaline phosphatase as predictors of calcium requirements after total parathyroidectomy for hypocalcemia in secondary hyperparathyroidism.

Head Neck. 2017 Sep 30;:

Authors: Ge P, Liu S, Sheng X, Li S, Xu M, Jiang J, Chen S

Abstract
BACKGROUND: To prevent hypocalcemia, this study examined the efficiency of a calcium supplement formula guided by predicted calcium requirement in patients with renal failure after parathyroidectomy with autotransplantation.
METHODS: In the first phase, a protocol was followed whereby intravenous calcium gluconate was repeatedly titrated based on serum calcium levels in 22 patients with parathyroidectomy with autotransplantation. In the second phase, the first equation protocol was applied in 74 patients with parathyroidectomy with autotransplantation and revised.
RESULTS: There is a significant correlation between the postoperative amount of calcium requirement and preoperative serum alkaline phosphatase level (r = 0.442; P < .001) and parathyroid hormone level (PTH; r = 0.889; P < .001). For prediction of insufficient calcium supplement, the cutoff point of PTH and alkaline phosphatase level values were calculated by receiver operating characteristic (ROC) curve analysis and modified equations were developed by regression analysis.
CONCLUSION: The preoperative PTH and alkaline phosphatase levels can predict postoperative calcium requirements, such that equations of calcium supplement allow the management of hypocalcemia efficiently in patients on dialysis after parathyroidectomy with autotransplantation.

PMID: 28963816 [PubMed - as supplied by publisher]

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Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma.

Predictors of survival after total laryngectomy for recurrent/persistent laryngeal squamous cell carcinoma.

Head Neck. 2017 Sep 30;:

Authors: Birkeland AC, Beesley L, Bellile E, Rosko AJ, Hoesli R, Chinn SB, Shuman AG, Prince ME, Wolf GT, Bradford CR, Brenner JC, Spector ME

Abstract
BACKGROUND: Total laryngectomy remains the treatment of choice for recurrent/persistent laryngeal squamous cell carcinoma (SCC) after radiotherapy (RT) or chemoradiotherapy (CRT). However, despite attempts at aggressive surgical salvage, survival in this cohort remains suboptimal.
METHODS: A prospectively maintained single-institution database was queried for patients undergoing total laryngectomy for recurrent/persistent laryngeal SCC after initial RT/CRT between 1998 and 2015(n = 244). Demographic, clinical, and survival data were abstracted. The Kaplan-Meier survival curves and hazard ratios (HRs) were calculated.
RESULTS: Five-year overall survival (OS) was 49%. Five-year disease-free survival (DFS) was 58%. Independent predictors of OS included severe comorbidity (Adult Comorbidity Evaluation-27 [ACE-27] scale; HR 3.76; 95% confidence interval [CI] 1.56-9.06), and positive recurrent clinical nodes (HR 2.91; 95% CI 1.74-4.88).
CONCLUSION: Severe comorbidity status is the strongest predictor of OS, suggesting that increased attention to mitigating competing risks to health is critical. These data may inform a risk prediction model to allow for focused shared decision making, preoperative health optimization, and patient selection for adjuvant therapies.

PMID: 28963806 [PubMed - as supplied by publisher]

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Justification of routine venous thromboembolism prophylaxis in head and neck cancer reconstructive surgery.

Justification of routine venous thromboembolism prophylaxis in head and neck cancer reconstructive surgery.

Head Neck. 2017 Sep 30;:

Authors: Ong HS, Gokavarapu S, Al-Qamachi L, Yin MY, Su LX, Ji T, Zhang CP

Abstract
BACKGROUND: Venous thromboembolism (VTE) is a preventable complication in which early ambulation is expected after head and neck surgery. Thus, the role of VTE prophylaxis is questionable and needs further assessment. The purpose of this study was to specify the relative contributing risk factors for patients who underwent head and neck cancer ablation with immediate reconstruction.
METHODS: A retrospective analysis was conducted of consecutive head and neck cancer ablations with immediate reconstructions between 2008 and 2013. Dextran and prostaglandin E2 (PGE2) were routinely given as flap thromboprophylaxis. Logistic regression was applied to analyze the potentially significant risk factors.
RESULTS: Of 1953 subjects, the incidence of symptomatic VTE was 2.2% with 0.1% mortality rate. Prolonged surgery (>592.5 minutes; P = .048), immobilization (>4 days; P = .019), and subjects without postoperative flap thromboprophylaxis (P = .002) are significant risk factors for VTE development.
CONCLUSION: Our flap thromboprophylaxis regime might have played a crucial role in keeping the incidence of VTE low. Despite prolonged immobilization in fibula flap reconstruction, the incidence of VTE remained low when flap thromboprophylaxis was given.

PMID: 28963805 [PubMed - as supplied by publisher]

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Cost analysis of a speech pathology synchronous telepractice service for patients with head and neck cancer.

Cost analysis of a speech pathology synchronous telepractice service for patients with head and neck cancer.

Head Neck. 2017 Sep 30;:

Authors: Burns CL, Kularatna S, Ward EC, Hill AJ, Byrnes J, Kenny LM

Abstract
BACKGROUND: The purpose of this study is to report the economic outcomes of a new synchronous telepractice service providing speech pathology intervention to patients with head and neck cancer at nonmetropolitan facilities.
METHODS: A multisite randomized controlled trial comparing standard care versus a new synchronous telepractice model was conducted within a large Australian public cancer service. Data pertaining to health service costs (staff wages, equipment, and patient travel reimbursement), patient +/- carer costs (travel and wages), and patient-reported quality of life (Assessment of Quality of Life questionnaire 4D) were collected.
RESULTS: Eighty-two referrals (39 standard care and 43 synchronous telepractice care) were managed. The new telepractice service reported average cost savings of 12% (P < .0058) for the health service and $40.05 saving per patient per referral. An equivalent positive increase in quality of life (0.04) was reported for both groups.
CONCLUSION: The synchronous telepractice service provides cost efficiencies over standard care for providing remote specialist speech pathology head and neck cancer intervention.

PMID: 28963804 [PubMed - as supplied by publisher]

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Event provides dental care to those who can't afford it

At least 1,500 people who can't afford dental care will get to see a dentist in Cedar Rapids. A group called "Not One Penny" has been running a T-V ad that attacks Republican Congressman Rod Blum.

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Normalized Study of Three-Parameter System in the Time Domain and Frequency Domain

Three-parameter isolation system can be used to isolate microvibration for control moment gyroscopes. Normalized analytical model for three-parameter system in the time domain and frequency domain is proposed by using analytical method. Dynamic behavior of three-parameter system in the time domain and frequency domain is studied. Response in the time domain under different types of excitations is analyzed. In this paper, a regulatory factor is defined in order to analyze dynamic behavior in the frequency domain. For harmonic excitation, a comparison study is made on isolation performance between the case when the system has optimal damping and the case when regulatory factor is 1. Besides, phase margin of three-parameter system is obtained. Results show that dynamic behavior in the time domain and frequency domain changes with regulatory factor. Phase margin has the largest value when the value of regulatory factor is 1. System under impulse excitation and step excitation has the shortest settling time for the response in the time domain when the value of regulatory factor is 1. When stiffness ratio is small, isolation performances of two cases are nearly the same; when system has a large stiffness ratio, isolation performance of the first case is better.

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Analyses of nucleotide, codon and amino acids usages between peste des petits ruminants virus and rinderpest virus

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Xiao-xia Ma, Qiu-yan Chang, Peng Ma, Lin-jie Li, Xiao-kai Zhou, De-rong Zhang, Ming-sheng Li, Xin Cao, Zhong-ren Ma
Peste des petits ruminants virus (PPRV) and rinderpest virus (RPV) are two causative agents of an economically important disease for ruminants (i.e., sheep, cattle and goat). In this study, the nucleotide, codon and amino acid usages for PPRV and RPV have been analyzed by multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis represents that ACG for Thr and GCG for Ala are selected with under-representation in both PPRV and RPV, and AGA for Arg in PPRV and AGG for Arg in RPV are used with over-representation. The usage of nucleotide pair (CpG) tends to be removed from viral genes of the two viruses, suggesting that other evolutionary forces take part in evolutionary processes for viral genes in addition to mutation pressure from nucleotide usage at the third codon position. The overall nucleotide usage of viral gene is not major factor in shaping synonymous codon usage patterns, while the nucleotide usages at the third codon position and the nucleotide pairs play important roles in shaping synonymous codon usage patterns. Although PPRV and RPV are closely related antigenically, the codon and amino acid usage patterns for viral genes represent a significant genetic diversity between PPRV and RPV. Moreover, the overall codon usage trends for viral genes between PPRV and RPV are mainly influenced by mutation pressure from nucleotide usage at the third codon position and translation selection from hosts. Taken together, this is first comprehensive analyses for nucleotide, codon and amino acid usages of viral genes of PPRV and RPV and the findings are expected to increase our understanding of evolutionary forces influencing viral evolutionary pathway and adaptation toward hosts.



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Polysaccharides isolated from Hedyotis diffusa inhibits the aggressive phenotypes of laryngeal squamous carcinoma cells via inhibition of Bcl-2, MMP-2, and μPA

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Caiqin Wu, Huanan Luo, Weijun Ma, Xiaoyong Ren, Chuangxin Lu, Ni Li, Zhenghui Wang
Hedyotis diffusa, a traditional Chinese herbal medicine, possesses anti-cancer, anti-oxidative, and anti-inflammatory effects. The aim of this study is to explore the anti-tumor potential of Hedyotis diffusa polysaccharides (HDP) in human larynx squamous carcinoma. High performance size-exclusion chromatography analysis indicated the homogeneous nature of HDP. Total carbohydrate content in HDP was 97.3%, without contamination of protein and nucleic acid. HDP suppressed the proliferation of Hep2 human larynx squamous carcinoma cells in a time- and dose-dependent manner. Cell cycle analysis revealed that exposure to HDP (400μg/ml) caused a G0/G1 cell cycle arrest. Moreover, treatment with HDP for 24h induced a significant apoptosis of Hep2 cells, which was accompanied by increased cleavage of caspase-3, caspase-8, and caspase-9 and reduced expression of Bcl-2 protein. Additionally, HDP inhibited cell migration and suppressed the expression of MMP-2 and μPA. In conclusion, HDP shows suppressive effects against the aggressive phenotypes of human larynx squamous carcinoma cells and may have therapeutic potential for this malignancy.



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Genome-wide analysis and expression profiles of NTMC2 family genes in Oryza sativa

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Rui Huang, Jin Zhao, Jin Liu, Yingdian Wang, Shengcheng Han, Heping Zhao
N-terminal-TM-C2 domain proteins (NTMC2), which share domain architecture and sequence similarity to synaptotagmins (Syts) in mammals and FAM62 (extended Syts) in metazoans, form a small gene family in plants. Previous studies showed that the Arabidopsis thaliana NTMC2 type 1.1 protein (NTMC2T1.1, named AtSyt1) possesses calcium- and membrane-binding activities that allow it to function in a plasma membrane repair pathway induced by stress. However, we lack understanding of the diverse biological roles of plant NTMC2 family genes. In this study, a total of 13 OsNTMC2 genes was identified through a comprehensive bioinformatics analysis of the rice (Oryza sativa L.) genome and classified into six OsNTMC2 groups (OsNTMC2T1 to OsNTMC2T6) based on phylogeny and motif constitution. OsNTMC2T1 to OsNTMC2T3 have two calcium-binding domains (C2A and C2B), but OsNTMC2T4 to OsNTMC2T6 have single C2 domain. The expression profiles of OsNTMC2 genes were analysed at different stages of vegetative and reproductive development. This analysis revealed that at least one OsNTMC2 gene was abundantly expressed at each stage of development. These results should facilitate research on this gene family and provide new insights elucidating their functions in higher plants.



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Glucose regulated protein 78 is potentially an important player in the development of nonalcoholic steatohepatitis

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Xin Zhou, Dewu Han, Xi Yang, Xiangyu Wang, Aixiu Qiao
Endoplasmic reticulum stress (ERS) plays an important role in metabolic diseases. Glucose regulated protein 78 (GRP78) is a molecular chaperone in the ER where it is a marker for ERS activation. This study investigates the role of GRP78 in the pathogenesis of nonalcoholic steatohepatitis (NASH) in rats. Our rat model of NASH was induced by both a high sucrose and a high fat diet. The expression levels of LPS, ALT, FFA, and TG in the serum and FFA, TG, MDA, and TNFα in the liver were assessed. H&E, TUNEL and IHC staining were performed to examine histological changes, apoptosis and macrophage infiltration in the NASH liver tissue, respectively. The expression level of GRP78 in the liver was evaluated by Western blot and RT-PCR. The plasma levels of LPS, ALT, FFA, and TG in and the contents of FFA, TG, TNFα, and MDA in the liver were gradually increased. Macrophage infiltration and hepatocytic apoptosis was significantly increased in the livers of the rats from the NASH group compared to the control group. The protein and mRNA levels of GRP78 in the liver of rats from the NASH group were also upregulated. In addition, GRP78 expression levels were positively correlated with the levels of ALT, TNFα, CD68 and hepatocytic apoptosis. Thus, our results suggest that GRP78 may be an important player in the pathogenesis of NASH.



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AGXT2 rs37369 polymorphism predicts the renal function in patients with chronic heart failure

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Xiao-Lei Hu, Wen-Jing Zeng, Mu-Peng Li, Yong-Long Yang, Da-Bin Kuang, He Li, Yan-Jiao Zhang, Chun Jiang, Li-Ming Peng, Hong Qi, Ke Zhang, Xiao-Ping Chen
Patients with chronic heart failure (CHF) are often accompanied with varying degrees of renal diseases. The purpose of this study was to identify rs37369 polymorphism of AGXT2 specific to the renal function of CHF patients. A total of 1012 southern Chinese participants, including 487 CHF patients without history of renal diseases and 525 healthy volunteers, were recruited for this study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes of AGXT2 rs37369 polymorphism. Levels of blood urea nitrogen (BUN) and serum creatinine (SCr) were detected to indicate the renal function of the participants. BUN level was significantly higher in CHF patients without history of renal diseases compared with healthy volunteers (p=0.000). And the similar result was also obtained for SCr (p=0.000). Besides, our results indicated that the level of BUN correlated significantly with SCr in both the CHF patients without renal diseases (r=0.4533, p<0.0001) and volunteers (r=0.2489, p<0.0001). Furthermore, we found that the AGXT2 rs37369 polymorphism could significantly affect the level of BUN in CHF patients without history of renal diseases (p=0.036, AA+AG vs GG). Patients with rs37369 GG genotype showed a significantly reduced level of BUN compared to those with the AA genotype (p=0.024), and the significant difference was still observed in the smokers of CHF patients without renal diseases (p=0.023). In conclusion, we found that CHF might induce the impairment of kidney and cause deterioration of renal function. AGXT2 rs37369 polymorphism might affect the renal function of CHF patients free from renal diseases, especially in patients with cigarette smoking.



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TRIM28 regulates Igf2-H19 and Dlk1-Gtl2 imprinting by distinct mechanisms during sheep fibroblast proliferation

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Jian Luo, Yiyuan Zhang, Yanhua Guo, Hong Tang, Haixia Wei, Shouren Liu, Xinhua Wang, Limin Wang, Ping Zhou
DNA methylation is an essential epigenetic modification involved in regulating gene expression and maintaining epigenetic information across generations. However, how these marks are recognized and interpreted to activate or repress imprinted genes is not fully understood. Preliminary evidence describes the transcriptional repressor TRIM28 as a key regulator of imprinted gene expression during and after early genome-wide reprogramming. Aberrant expression of imprinted genes maybe one possible cause of incomplete epigenetic reprogramming and low efficiency in somatic cell nuclear transfer. Here, we perform a series of experiments to determine whether knockdown of Trim28 alters imprinted gene expression and DMR methylation in sheep embryonic fibroblast (SEF) cells. siRNA-mediated Trim28 silencing in SEF cells resulted in significantly decreased expression of Gtl2 to 30% and increased expression of Dlk1 (~1.7-fold). Moreover, knocking down Trim28 induced DNA methylation at the IG-DMR and the Gtl2 promoter was disrupted. Here, we uncover an important role for Trim28 in the maintenance of DNA methylation at IG-DMR during replication-dependent dilution of methylated cytosine during cellular proliferation. Unlike Dlk1-Gtl2 however, knocking down Trim28 does not affect DMR methylation in the Igf2-H19 gene cluster, yet results in increased expression of Igf2 and H19. Interestingly, Peg3 expression decreased by 60% in Trim28 knockdown cells. PEG3 as a transcriptional repressor to the H19-ICR that interacts with the co-repressor protein TRIM28 through KRAB-A. Trim28 therefore appears to control the Igf2-H19 imprinted cluster indirectly via PEG3, which is distinct from its classical role in preserving DNA methylation during DNA replication. Our results therefore indicate that Trim28 regulates imprinted gene expression through at least two distinct mechanisms during cells proliferation.



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Polymorphisms of the folate metabolizing enzymes: Association with SLE susceptibility and in silico analysis

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Saeedeh Salimi, Farshid Keshavarzi, Abbas Mohammadpour-Gharehbagh, Mahdieh Moodi, Mahdieh Mousavi, Mohammad Karimian, Mahnaz Sandoughi
Systemic lupus erythematosus (SLE) is a typical autoimmune disorder with multiple organ involvement and unknown etiology. It has been shown that polymorphic variants of the genes encoding key enzymes of folate and methionine metabolism may influence DNA methylation. Genomic DNA was extracted from blood samples of 150 SLE patients and 160 controls, matching age, sex, and ethnicity. MTHFR rs1801133C>T and MTR rs1805087A>G polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. MTHFR rs1801131A>C genotype was determined by the tetra-primer amplification refractory mutation system (Tetra-ARMS), and DHFR rs70991108 polymorphisms' genotyping was performed by PCR methods. In-silico approach was used to analyses the effects of these variations on the structure of mRNA and protein. MTHFR rs1801131AC+CC genotypes were significantly higher in the SLE patients compared to the controls (37 vs. 26%, OR 1.7 (95% CI 1–2.8); p=0.03). The frequency of MTHFR rs1801131C allele was significantly higher in the SLE patients than the controls (22 vs. 15%, p=0.02). However, there was no association between MTHFR rs1801133C>T polymorphism and SLE. The frequency of CT haplotype of MTHFR rs1801133C>T and rs1801131A>C polymorphisms was significantly higher in the SLE patients (20 vs. 12%), and CT haplotype may be potentially a risk factor for SLE susceptibility [OR 1.9 (95% CI 1.2–2.9); p=0.006]. There was no association between alleles and genotypes of DHFR rs70991108 polymorphism and SLE susceptibility. The frequency of MTR rs1805087AG genotype was less frequent in the SLE patients compared to the controls, and this genotype could decrease the SLE risk (35 vs. 48%), (OR, 0.6 (95% CI, 0.4 to 0.9), p=0.03). In silico-analysis showed that both of MTHFR rs1801133C>T and rs1801131A>C SNPs made fundamental changes in the secondary structure of MTHFR-mRNA (p=0.0412 and p=0.1641; p<0.2). Also, structural analysis of the rs1801131A>C variation showed a significant effect on MTHFR function. Bioinformatics analysis showed that rs70991108 polymorphism in DHFR gene would lead to a significant alteration of the splicing process. In conclusion, MTHFR rs1801131 AC+CC genotypes could be a risk factor and MTR rs1805087AG genotype could be a protective factor for SLE susceptibility. There was no association between MTHFR rs1801133C>T and DHFR rs70991108 polymorphisms and SLE.



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Comparative effect of imatinib and ponatinib on autophagy and miRNome in chronic myeloid leukemia

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Cagla Kayabasi, Tugce Balci Okcanoglu, Besra Ozmen Yelken, Aycan Asik, Sunde Yilmaz Susluer, Cigir Biray Avci, Guray Saydam, Cumhur Gunduz
BCR-ABL tyrosine kinase inhibitors (TKIs) are selective therapies for the patients with Chronic Myeloid Leukemia (CML). Imatinib and ponatinib have remarkable long-term efficacy on a major molecular response. Although TKI related induction of cytotoxicity and apoptosis have been clearly investigated in molecular levels, their comparative effect on autophagy and miRNome are largely unknown. This study aimed to investigate the involvement of alterations of miRNA expressions in CML progression, and how imatinib and ponatinib affect this process, by comparing CML, imatinib-resistant CML and leukemia stem cells (LSC). Cytotoxicity analysis was conducted by WST-1, apoptosis was evaluated by AnnexinV, autophagy was analyzed by Tb/GFP TR-FRET LC3B assay and changes in miRNomes were evaluated with microarray method. Ponatinib showed higher cytotoxicity and apoptosis at far fewer concentrations than imatinib. Both imatinib and ponatinib was able to trigger autophagy in imatinib-resistant K562ima3 cell line but not in LSC. We pointed that imatinib and ponatinib caused significant miRNA profile alterations, especially in the expressions of miR-214-pre, miR-218, miR-19a-5p, miR-19b-1-5p, miR-27b-pre, miR-23b-pre, miR-320e, miR-200a-pre, miR-508-3p, miR-33-pre and miR-766. This study is the first comparative miRNome analysis of CML, resistant CML and LSCs following the imatinib or ponatinib treatment and may guide to identify new markers for diagnosis, follow-up of the disease and to develop novel therapeutic strategies if supported by preclinical studies.



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Heterogenous expression of Pyrus pyrifolia PpCAD2 and PpEXP2 in tobacco impacts lignin accumulation in transgenic plants

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Yuling Wang, Xinfu Zhang, Shaolan Yang, Caihong Wang, Guilong Lu, Ran Wang, Yingjie Yang, Dingli Li
Lignin, a natural macromolecular compound, plays an important role in the texture and taste of fruit. Hard end is a physiological disorder of pear fruit, in which the level of lignification in fruit tissues is dramatically elevated. Cinnamyl alcohol dehydrogenase and expansin genes (PpCAD2 and PpEXP2, respectively) exhibit higher levels of expression in 'Whangkeumbae' (Pyrus pyrifolia) pear fruit exhibiting this physiological disorder, relative to control fruit without symptoms. These genes were isolated from pear fruit and subsequently expressed in tobacco (Nicotiana tabacum) to investigate their function. Histochemical staining for lignin revealed that the degree of lignification in leaf veins and stem tissues increased in plants transformed with sense constructs and decreased in plants transformed with antisense constructs of PpCAD2. The expression of native NtCADs was also inhibited in the antisense PpCAD2 transgenic tobacco. Sense and antisense PpCAD2 transgenic tobacco exhibited an 86.7% increase and a 60% decrease in CAD activity, respectively, accompanied by a complementary response in lignin content in root tissues. The basal portion of the stem in PpEXP2 transgenic tobacco was bent and highly lignified. Additionally, the level of cellulose also increased in the stem of PpEXP2 transgenic tobacco. Collectively, these results suggested that PpCAD2 and PpEXP2 genes play a significant role in lignin accumulation in transgenic tobacco plants, and it is inferred that these two genes may also participate in the increased lignification observed in hard end pear fruit.



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Gender differences in the association of ENPP1 polymorphisms with type 2 diabetes in a Chinese population

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Lulin Chen, Yingfen Qin, Danyan Liang, Xinghuan Liang, Yaojie Liang, Li Li, Jing Xian, Lulu Zhang, Lei Tong, Hong Li, Haiying Zhang
BackgroundEctonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) encodes the human plasma-cell membrane differentiation antigen-1, and ENPP1 variants have been shown to be associated with type 2 diabetes (T2D) and insulin resistance. In this study, we investigated the involvement of ENPP1 polymorphisms in T2D.MethodsThe association of the two polymorphisms of ENPP1 (rs7754586 and rs55725924) with T2D and diabetes-related quantitative traits was analyzed in Chinese samples containing 929 T2D patients and 1044 healthy individuals. We also performed the expression quantitative trait loci (eQTL) analysis to study the association of both polymorphisms of ENPP1 with mRNA expression levels using the genotype-tissue expression database.ResultsThe risk allele A of the polymorphism rs7754586 contributed to T2D (odds ratio: 1.252, 95% confidence interval: 1.044–1.615, P=0.018). The polymorphism rs55725924 was associated with the diastolic blood pressure and cholesterol levels. Patients carrying high-risk haplotype A-T of rs7754586 and rs55725924 exhibited a high risk of acquiring T2D. These associations were only observed in males, but not in females. In addition, the eQTL analysis demonstrated that the risk allele of rs7754586 was associated with higher levels of ENPP1 mRNA expression.ConclusionOur findings suggest that the ENPP1 polymorphism rs7754586 may implicate in the pathogenesis of T2D in men, while polymorphism rs55725924 may be involved in diastolic blood pressure and cholesterol of male T2D patients.



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Epidermal long non-coding RNAs are regulated by ultraviolet irradiation

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Kyu-Han Kim, Hyoung-June Kim, Tae Ryong Lee
Ultraviolet (UV) radiation causes the harmful effects on skin by the photochemical reaction and gene expression regulation. Recent evidences have shown that long non-coding RNAs (lncRNAs) play critical roles in a diverse range of biological functions. However, research on the effects of UV irradiation on lncRNA expression in epidermal cells is limited. The aim of this study was to identify changes in the expression profile of lncRNAs after UVB irradiation. To accomplish this, we performed a microarray analysis of both mRNA and lncRNA expression levels in irradiated skin cells. Gene ontology (GO) analysis of differentially expressed mRNAs showed that the expression of immune response- and cell membrane-related genes was up-regulated, while cell-cell adhesion-associated genes were down-regulated by UVB irradiation. Moreover, we found that lncRNAs up-regulated by UVB irradiation were associated with the regulation of gene transcription, while lncRNAs down-regulated by UVB irradiation were associated with tumorigenesis. Finally, we compiled a list of the lncRNAs that showed the strongest association with the development of non-melanoma skin cancers caused by UV exposure. These findings lay a foundation for future investigations into the expression patterns of lncRNAs with roles in the response to UV irradiation and in non-melanoma skin cancers.



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Comparative transcriptome analysis of ovary and testis reveals potential sex-related genes and pathways in spotted knifejaw Oplegnathus punctatus

Publication date: 30 December 2017
Source:Gene, Volume 637
Author(s): Xinxin Du, Bo Wang, Xiumei Liu, Xiaobing Liu, Yan He, Quanqi Zhang, Xubo Wang
The spotted knifejaw (Oplegnathus punctatus) is a newly emerging fishery species inhabiting the Pacific Ocean around Hawaii, China, Japan and Korean Peninsula. Little information on the mechanism of gonadal development and gametogenesis in this species could be used for research and breeding work. In this study, RNA-seq technology was applied to generate a deep-coverage sequencing data of spotted knifejaw testis and ovary. A total of 262,392,754 reads (ovary 133,403,270, testis 128,989,484) were generated from the cDNA library. After filtering and assembling, a total of 113,794 unigenes were obtained with the N50 of 1658bp. Unigenes were annotated with multiple public databases, including non-redundant protein databases (NR) (42,460, 37.31%), Swiss-Prot (33,632, 29.56%), eukaryotic Orthologus Groups (KOG) (26,195, 23.02%), Kyoto Encyclopedia of Genes and Genomes (KEGG) (10,978, 9.65%), and Gene Ontology (GO) (30,514, 26.82%). By comparing ovary and testis, 4496 differentially expressed unigenes (1986 in female, 2510 in male) were identified, in which 469 were specially expressed in females and 859 in males. The expression levels of 12 unigenes were confirmed by qRT-PCR. In addition, 35,054 simple sequence repeats were identified. By GO and KEGG analyses, a set of unigenes related to gonadal development and gametogenesis were filtered. foxl2 was deduced to be a key regulator for gonadal development and gametogenesis in females and dmrt1 in males. bmp15, nanos3, sox9 and amh were likely to function in the regulation of gonad physiology and germ line cells maintenance in ovary and testis. Interestingly, p53, apoptosis, Jak-STAT and neuroactive ligand-receptor interaction pathways were found to be pivotal in regulating gonadal development and gametogenesis of spotted knifejaw in various aspects. This study provides a fundamental support for further research in reproduction biology, population genetics and functional genomics in spotted knifejaw.



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Chemoproteomics Reveals Chemical Diversity and Dynamics of 4-Oxo-2-nonenal Modifications in Cells [Research]

4-Oxo-2-nonenal (ONE) derived from lipid peroxidation modifies nucleophiles and transduces redox signaling by its reactions with proteins. However, the molecular interactions between ONE and complex proteomes and their dynamics in situ remain largely unknown. Here we describe a quantitative chemoproteomic analysis of protein adduction by ONE in cells, in which the cellular target profile of ONE is mimicked by its alkynyl surrogate. The analyses reveal four types of ONE-derived modifications in cells, including ketoamide and Schiff-base adducts to lysine, Michael adducts to cysteine, and a novel pyrrole adduct to cysteine. ONE-derived adducts co-localize and exhibit crosstalk with many histone marks and redox sensitive sites. All four types of modifications derived from ONE can be reversed site-specifically in cells. Taken together, our study provides much-needed mechanistic insights into the cellular signaling and potential toxicities associated with this important lipid derived electrophile.

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Identification of Differentially Expressed Splice Variants by the Proteogenomic Pipeline Splicify [Technological Innovation and Resources]

Proteogenomics, i.e. comprehensive integration of genomics and proteomics data, is a powerful approach identifying novel protein biomarkers. This is especially the case for proteins that differ structurally between disease and control conditions. As tumor development is associated with aberrant splicing, we focus on this rich source of cancer specific biomarkers. To this end, we developed a proteogenomic pipeline, Splicify, which can detect differentially expressed protein isoforms. Splicify is based on integrating RNA massive parallel sequencing data and tandem mass spectrometry proteomics data to identify protein isoforms resulting from differential splicing between two conditions. Proof of concept was obtained by applying Splicify to RNA sequencing and mass spectrometry data obtained from colorectal cancer cell line SW480, before and after siRNA-mediated downmodulation of the splicing factors SF3B1 and SRSF1. These analyses revealed 2172 and 149 differentially expressed isoforms, respectively, with peptide confirmation upon knock-down of SF3B1 and SRSF1 compared with their controls. Splice variants identified included RAC1, OSBPL3, MKI67, and SYK. One additional sample was analyzed by PacBio Iso-Seq full-length transcript sequencing after SF3B1 downmodulation. This analysis verified the alternative splicing identified by Splicify and in addition identified novel splicing events that were not represented in the human reference genome annotation. Therefore, Splicify offers a validated proteogenomic data analysis pipeline for identification of disease specific protein biomarkers resulting from mRNA alternative splicing. Splicify is publicly available on GitHub (http://ift.tt/2vJm0Ez) and suitable to address basic research questions using pre-clinical model systems as well as translational research questions using patient-derived samples, e.g. allowing to identify clinically relevant biomarkers.

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Development of a Multiplexed Assay for Oral Cancer Candidate Biomarkers Using Peptide Immunoaffinity Enrichment and Targeted Mass Spectrometry [Research]

Oral cancer is one of the most common cancers worldwide, and there are currently no biomarkers approved for aiding its management. Although many potential oral cancer biomarkers have been discovered, very few have been verified in body fluid specimens in parallel to evaluate their clinical utility. The lack of appropriate multiplexed assays for chosen targets represents one of the bottlenecks to achieving this goal. In the present study, we develop a peptide immunoaffinity enrichment-coupled multiple reaction monitoring-mass spectrometry (SISCAPA-MRM) assay for verifying multiple reported oral cancer biomarkers in saliva. We successfully produced 363 clones of mouse anti-peptide monoclonal antibodies (mAbs) against 36 of 49 selected targets, and characterized useful mAbs against 24 targets in terms of their binding affinity for peptide antigens and immuno-capture ability. Comparative analyses revealed that an equilibrium dissociation constant (K_D) cut-off value < 2.82 x 10^–9m could identify most clones with an immuno-capture recovery rate >5%. Using these mAbs, we assembled a 24-plex SISCAPA-MRM assay and optimized assay conditions in a 25-μg saliva matrix background. This multiplexed assay showed reasonable precision (median coefficient of variation, 7.16 to 32.09%), with lower limits of quantitation (LLOQ) of <10, 10–50, and >50 ng/ml for 14, 7 and 3 targets, respectively. When applied to a model saliva sample pooled from oral cancer patients, this assay could detect 19 targets at higher salivary levels than their LLOQs. Finally, we demonstrated the utility of this assay for quantification of multiple targets in individual saliva samples (20 healthy donors and 21 oral cancer patients), showing that levels of six targets were significantly altered in cancer compared with the control group. We propose that this assay could be used in future studies to compare the clinical utility of multiple oral cancer biomarker candidates in a large cohort of saliva samples.

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Identification of the SOX2 Interactome by BioID Reveals EP300 as a Mediator of SOX2-dependent Squamous Differentiation and Lung Squamous Cell Carcinoma Growth [Research]

Lung cancer is the leading cause of cancer mortality worldwide, with squamous cell carcinoma (SQCC) being the second most common form. SQCCs are thought to originate in bronchial basal cells through an injury response to smoking, which results in this stem cell population committing to hyperplastic squamous rather than mucinous and ciliated fates. Copy number gains in SOX2 in the region of 3q26–28 occur in 94% of SQCCs, and appear to act both early and late in disease progression by stabilizing the initial squamous injury response in stem cells and promoting growth of invasive carcinoma. Thus, anti-SOX2 targeting strategies could help treat early and/or advanced disease. Because SOX2 itself is not readily druggable, we sought to characterize SOX2 binding partners, with the hope of identifying new strategies to indirectly interfere with SOX2 activity. We now report the first use of proximity-dependent biotin labeling (BioID) to characterize the SOX2 interactome in vivo. We identified 82 high confidence SOX2-interacting partners. An interaction with the coactivator EP300 was subsequently validated in both basal cells and SQCCs, and we demonstrate that EP300 is necessary for SOX2 activity in basal cells, including for induction of the squamous fate. We also report that EP300 copy number gains are common in SQCCs and that growth of lung cancer cell lines with 3q gains, including SQCC cells, is dependent on EP300. Finally, we show that EP300 inhibitors can be combined with other targeted therapeutics to achieve more effective growth suppression. Our work supports the use of BioID to identify interacting protein partners of nondruggable oncoproteins such as SOX2, as an effective strategy to discover biologically relevant, druggable targets.

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An Integrated Approach to Explore Composition and Dynamics of Cholesterol-rich Membrane Microdomains in Sexual Stages of Malaria Parasite [Research]

Membrane microdomains that include lipid rafts, are involved in key physiological and pathological processes and participate in the entry of endocellular pathogens. These assemblies, enriched in cholesterol and sphingolipids, form highly dynamic, liquid-ordered phases that can be separated from the bulk membranes thanks to their resistance to solubilization by nonionic detergents. To characterize complexity and dynamics of detergent-resistant membranes of sexual stages of the rodent malaria parasite Plasmodium berghei, here we propose an integrated study of raft components based on proteomics, lipid analysis and bioinformatics. This analysis revealed unexpected heterogeneity and unexplored pathways associated with these specialized assemblies. Protein-protein relationships and protein-lipid co-occurrence were described through multi-component networks. The proposed approach can be widely applied to virtually every cell type in different contexts and perturbations, under physiological and/or pathological conditions.

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Systematic and Quantitative Assessment of Hydrogen Peroxide Reactivity With Cysteines Across Human Proteomes [Research]

Protein cysteinyl residues are the mediators of hydrogen peroxide (H₂O₂)-dependent redox signaling. However, site-specific mapping of the selectivity and dynamics of these redox reactions in cells poses a major analytical challenge. Here we describe a chemoproteomic platform to systematically and quantitatively analyze the reactivity of thousands of cysteines toward H₂O₂ in human cells. We identified >900 H₂O₂-sensitive cysteines, which are defined as the H₂O₂-dependent redoxome. Although redox sites associated with antioxidative and metabolic functions are consistent, most of the H₂O₂-dependent redoxome varies dramatically between different cells. Structural analyses reveal that H₂O₂-sensitive cysteines are less conserved than their redox-insensitive counterparts and display distinct sequence motifs, structural features, and potential for crosstalk with lysine modifications. Notably, our chemoproteomic platform also provides an opportunity to predict oxidation-triggered protein conformational changes. The data are freely accessible as a resource at http://ift.tt/2vXVSpP.

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pyQms enables universal and accurate quantification of mass spectrometry data [Technological Innovation and Resources]

Quantitative mass spectrometry (MS) is a key technique in many research areas (1), including proteomics, metabolomics, glycomics, and lipidomics. Because all of the corresponding molecules can be described by chemical formulas, universal quantification tools are highly desirable. Here, we present pyQms, an open-source software for accurate quantification of all types of molecules measurable by MS. pyQms uses isotope pattern matching that offers an accurate quality assessment of all quantifications and the ability to directly incorporate mass spectrometer accuracy. pyQms is, due to its universal design, applicable to every research field, labeling strategy, and acquisition technique. This opens ultimate flexibility for researchers to design experiments employing innovative and hitherto unexplored labeling strategies. Importantly, pyQms performs very well to accurately quantify partially labeled proteomes in large scale and high throughput, the most challenging task for a quantification algorithm.

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Dormancy in Embryos: Insight from Hydrated Encysted Embryos of an Aquatic Invertebrate [Research]

Numerous aquatic invertebrates remain dormant for decades in a hydrated state as encysted embryos. In search for functional pathways associated with this form of dormancy, we used label-free quantitative proteomics to compare the proteomes of hydrated encysted dormant embryos (resting eggs; RE) with nondormant embryos (amictic eggs; AM) of the rotifer Brachionus plicatilis.

A total of 2631 proteins were identified in rotifer eggs. About 62% proteins showed higher abundance in AM relative to RE (Fold Change>3; p = 0.05). Proteins belonging to numerous putative functional pathways showed dramatic changes during dormancy. Most striking were changes in the mitochondria indicating an impeded metabolism. A comparison between the abundance of proteins and their corresponding transcript levels, revealed higher concordance for RE than for AM. Surprisingly, numerous highly abundant dormancy related proteins show corresponding high mRNA levels in metabolically inactive RE. As these mRNAs and proteins degrade at the time of exit from dormancy they may serve as a source of nucleotides and amino acids during the exit from dormancy. Because proteome analyses point to a similarity in functional pathways of hydrated RE and desiccated life forms, REs were dried. Similar hatching and reproductive rates were found for wet and dried REs, suggesting analogous pathways for long-term survival in wet or dry forms. Analysis by KEGG pathways revealed a few general strategies for dormancy, proposing an explanation for the low transcriptional similarity among dormancies across species, despite the resemblance in physiological phenotypes.

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Identification of Fc Gamma Receptor Glycoforms That Produce Differential Binding Kinetics for Rituximab [Research]

Fc gamma receptors (FcR) bind the Fc region of antibodies and therefore play a prominent role in antibody-dependent cell-based immune responses such as ADCC, CDC and ADCP. The immune effector cell activity is directly linked to a productive molecular engagement of FcRs where both the protein and glycan moiety of antibody and receptor can affect the interaction and in the present study we focus on the role of the FcR glycans in this interaction. We provide a complete description of the glycan composition of Chinese hamster ovary (CHO) expressed human Fc receptors RI (CD64), RIIa_{Arg131/His131} (CD32a), RIIb (CD32b) and RIIIa_{Phe158/Val158} (CD16a) and analyze the role of the glycans in the binding mechanism with IgG. The interactions of the monoclonal antibody rituximab with each FcR were characterized and we discuss the CHO-FcRIIIa_{Phe158/Val158} and CHO-FcRI interactions and compare them to the equivalent interactions with human (HEK293) and murine (NS0) produced receptors. Our results reveal clear differences in the binding profiles of rituximab, which we attribute in each case to the differences in host cell-dependent FcR glycosylation. The glycan profiles of CHO expressed FcRI and FcRIIIa_{Phe158/Val158} were compared with the glycan profiles of the receptors expressed in NS0 and HEK293 cells and we show that the glycan type and abundance differs significantly between the receptors and that these glycan differences lead to the observed differences in the respective FcR binding patterns with rituximab. Oligomannose structures are prevalent on FcRI from each source and likely contribute to the high affinity rituximab interaction through a stabilization effect. On FcRI and FcRIIIa large and sialylated glycans have a negative impact on rituximab binding, likely through destabilization of the interaction. In conclusion, the data show that the IgG1-FcR binding kinetics differ depending on the glycosylation of the FcR and further support a stabilizing role of FcR glycans in the antibody binding interaction.

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Characterization of the CLASP2 Protein Interaction Network Identifies SOGA1 as a Microtubule-Associated Protein [Research]

CLASP2 is a microtubule-associated protein that undergoes insulin-stimulated phosphorylation and co-localization with reorganized actin and GLUT4 at the plasma membrane. To gain insight to the role of CLASP2 in this system, we developed and successfully executed a streamlined interactome approach and built a CLASP2 protein network in 3T3-L1 adipocytes. Using two different commercially available antibodies for CLASP2 and an antibody for epitope-tagged, overexpressed CLASP2, we performed multiple affinity purification coupled with mass spectrometry (AP-MS) experiments in combination with label-free quantitative proteomics and analyzed the data with the bioinformatics tool Significance Analysis of Interactome (SAINT). We discovered that CLASP2 coimmunoprecipitates (co-IPs) the novel protein SOGA1, the microtubule-associated protein kinase MARK2, and the microtubule/actin-regulating protein G2L1. The GTPase-activating proteins AGAP1 and AGAP3 were also enriched in the CLASP2 interactome, although subsequent AGAP3 and CLIP2 interactome analysis suggests a preference of AGAP3 for CLIP2. Follow-up MARK2 interactome analysis confirmed reciprocal co-IP of CLASP2 and revealed MARK2 can co-IP SOGA1, glycogen synthase, and glycogenin. Investigating the SOGA1 interactome confirmed SOGA1 can reciprocal co-IP both CLASP2 and MARK2 as well as glycogen synthase and glycogenin. SOGA1 was confirmed to colocalize with CLASP2 and with tubulin, which identifies SOGA1 as a new microtubule-associated protein. These results introduce the metabolic function of these proposed novel protein networks and their relationship with microtubules as new fields of cytoskeleton-associated protein biology.

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Quantitative Mass Spectrometry Analysis of PD-L1 Protein Expression, N-glycosylation and Expression Stoichiometry with PD-1 and PD-L2 in Human Melanoma [Research]

Quantitative assessment of key proteins that control the tumor-immune interface is one of the most formidable analytical challenges in immunotherapeutics. We developed a targeted MS platform to quantify programmed cell death-1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and programmed cell death 1 ligand 2 (PD-L2) at fmol/microgram protein levels in formalin fixed, paraffin-embedded sections from 22 human melanomas. PD-L1 abundance ranged 50-fold, from ~0.03 to 1.5 fmol/microgram protein and the parallel reaction monitoring (PRM) data were largely concordant with total PD-L1-positive cell content, as analyzed by immunohistochemistry (IHC) with the E1L3N antibody. PD-1 was measured at levels up to 20-fold lower than PD-L1, but the abundances were not significantly correlated (r² = 0.062, p = 0.264). PD-1 abundance was weakly correlated (r² = 0.3057, p = 0.009) with the fraction of lymphocytes and histiocytes in sections. PD-L2 was measured from 0.03 to 1.90 fmol/microgram protein and the ratio of PD-L2 to PD-L1 abundance ranged from 0.03 to 2.58. In 10 samples, PD-L2 was present at more than half the level of PD-L1, which suggests that PD-L2, a higher affinity PD-1 ligand, is sufficiently abundant to contribute to T-cell downregulation. We also identified five branched mannose and N-acetylglucosamine glycans at PD-L1 position N192 in all 22 samples. Extent of PD-L1 glycan modification varied by ~10-fold and the melanoma with the highest PD-L1 protein abundance and most abundant glycan modification yielded a very low PD-L1 IHC estimate, thus suggesting that N-glycosylation may affect IHC measurement and PD-L1 function. Additional PRM analyses quantified immune checkpoint/co-regulator proteins LAG3, IDO1, TIM-3, VISTA, and CD40, which all displayed distinct expression independent of PD-1, PD-L1, and PD-L2. Targeted MS can provide a next-generation analysis platform to advance cancer immuno-therapeutic research and diagnostics.

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Supersonic car project aims to carry kids to a scientific future

Bloodhound is using its world land speed record attempt to inspire the next generation of UK scientists and engineers through workshops run by its charity arm

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Compression of the Femoral Vessels by a Pseudotumor after Metal-on-Metal Total Hip Arthroplasty

Here we present a case of pseudotumor following total hip arthroplasty (THA) that resulted in a circulatory disturbance caused by compression of the femoral vasculature. A 63-year-old man presented with pain, swelling, and redness of the left leg 5 years after primary metal-on-metal THA using the AML-Plus stem, Pinnacle® acetabular cup, and 36 mm diameter Ultamet™ metal head system (DePuy Orthopaedics, Warsaw, IN). Enhanced computed tomography and magnetic resonance imaging revealed a large cystic lesion extending from the left hip anteriorly to the intrapelvic region and compressing the left femoral vessels. Percutaneous puncture of the lesion yielded a dark red aspirate and the patient was diagnosed to have a pseudotumor causing compression of the femoral vessels. We performed revision surgery to replace the metal head and metal liner with a smaller ceramic head and polyethylene liner without removal of the stem. Corrosion of the head-neck junction was identified intraoperatively with no obvious wear on the bearing surfaces. The left leg swelling and redness improved immediately postoperatively. A large pseudotumor should be kept in mind as a cause of vascular compression with unilateral leg edema in a patient who has undergone metal-on-metal THA.

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Characteristic Analysis of Mixed Traffic Flow of Regular and Autonomous Vehicles Using Cellular Automata

The technology of autonomous vehicles is expected to revolutionize the operation of road transport systems. The penetration rate of autonomous vehicles will be low at the early stage of their deployment. It is a challenge to explore the effects of autonomous vehicles and their penetration on heterogeneous traffic flow dynamics. This paper aims to investigate this issue. An improved cellular automaton was employed as the modeling platform for our study. In particular, two sets of rules for lane changing were designed to address mild and aggressive lane changing behavior. With extensive simulation studies, we obtained some promising results. First, the introduction of autonomous vehicles to road traffic could considerably improve traffic flow, particularly the road capacity and free-flow speed. And the level of improvement increases with the penetration rate. Second, the lane-changing frequency between neighboring lanes evolves with traffic density along a fundamental-diagram-like curve. Third, the impacts of autonomous vehicles on the collective traffic flow characteristics are mainly related to their smart maneuvers in lane changing and car following, and it seems that the car-following impact is more pronounced.

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Epileptic MEG Spike Detection Using Statistical Features and Genetic Programming with KNN

Epilepsy is a neurological disorder that affects millions of people worldwide. Monitoring the brain activities and identifying the seizure source which starts with spike detection are important steps for epilepsy treatment. Magnetoencephalography (MEG) is an emerging epileptic diagnostic tool with high-density sensors; this makes manual analysis a challenging task due to the vast amount of MEG data. This paper explores the use of eight statistical features and genetic programing (GP) with the K-nearest neighbor (KNN) for interictal spike detection. The proposed method is comprised of three stages: preprocessing, genetic programming-based feature generation, and classification. The effectiveness of the proposed approach has been evaluated using real MEG data obtained from 28 epileptic patients. It has achieved a 91.75% average sensitivity and 92.99% average specificity.

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Influence of Overnight Orthokeratology on Corneal Surface Shape and Optical Quality

Purpose. To investigate the changes of corneal surface shape and optical quality during orthokeratology. Methods. 49 eyes of 26 patients (10.63 ± 2.02 years old) who underwent overnight orthokeratology for myopia were prospectively examined. The corneal surface shape parameters, including surface regularity index (SRI) and surface asymmetry index (SAI), were attained with an OPD-III SCAN. The higher-order aberrations and higher-order Strehl ratios were calculated under a 3 mm pupil diameter before orthokeratology, 1 month, 3 months, and 6 months after orthokeratology. A value of less than 0.05 was statistically significant. Results. Months after orthokeratology, SRI and SAI were both showing a significant increase in comparison with those before orthokeratology (). After orthokeratology, for a 3 mm pupil, the higher-order Strehl ratio presented a reduction of 0.217 μm (), and the higher-order aberration root mean square (HOA RMS) showed a mean increase of 0.100 μm (). There were significant increases in spherical aberration () and coma () after orthokeratology. Trefoil showed a slight reduction at month 6 after orthokeratology, but there was no statistical significance (). Conclusion. Overnight orthokeratology for a correction of myopia resulted in a significant improvement in refractive error but increased corneal irregularity and ocular higher-order aberrations, especially in spherical aberration.

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Effect of Indium Additions on the Formation of Interfacial Intermetallic Phases and the Wettability at Sn-Zn-In/Cu Interfaces

The wettability of copper substrates by Sn-Zn eutectic solder alloy doped with 0, 0.5, 1, and 1.5 at.% of indium was studied using the sessile drop method, with flux, in air, at 250°C and reflow time of 3, 8, 15, 30, and 60 min. Wetting tests were performed at 230, 250, 280, 320, and 370°C for an alloy containing 1.5 at.% of indium, in order to determine activation energy of diffusion. Solidified solder/substrate couples were studied using scanning electron microscopy (SEM), the intermetallic phases from Cu-Zn system which formed at the solder/substrate interface were identified, and their growth kinetics was investigated. The ε-CuZn4 was formed first, as a product of the reaction between liquid solder and the Cu substrate, whereas γ-Cu5Zn8 was formed as a product of the reaction between ε-CuZn4 and the Cu substrate. With increasing wetting time, the thickness of ε-CuZn4 increases, while the thickness of ε-CuZn4 does not change over time for indium-doped solders and gradually disappears over time for Sn-Zn eutectic solder.

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Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation

Inflammation may be defined as the innate response to harmful stimuli such as pathogens, injury, and metabolic stress; its ultimate function is to restore the physiological homeostatic state. The exact aetiology leading to the development of inflammation is not known, but a combination of genetic, epigenetic, and environmental factors seems to play an important role in the pathogenesis of many inflammation-related clinical conditions. Recent studies suggest that the pathogenesis of different inflammatory diseases also involves the inflammasomes, intracellular multiprotein complexes that mediate activation of inflammatory caspases thereby inducing the secretion of proinflammatory cytokines. Melatonin, an endogenous indoleamine, is considered an important multitasking molecule with fundamental clinical applications. It is involved in mood modulation, sexual behavior, vasomotor control, and immunomodulation and influences energy metabolism; moreover, it acts as an oncostatic and antiaging molecule. Melatonin is an important antioxidant and also a widespread anti-inflammatory molecule, modulating both pro- and anti-inflammatory cytokines in different pathophysiological conditions. This review, first, gives an overview concerning the growing importance of melatonin in the inflammatory-mediated pathological conditions and, then, focuses on its roles and its protective effects against the activation of the inflammasomes and, in particular, of the NLRP3 inflammasome.

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PDE5 Overexpression in Well-Differentiated Thyroid Carcinomas Is Associated with Lymph Node Metastasis

Overexpression of PDE5 is observed in certain human cancers, but PDE5 expression in well-differentiated thyroid carcinoma (WDTC) is unknown. We therefore examined PDE5 expression and its relationship with the clinicopathological features of WDTC. Real-time qPCR and Western blotting were performed to analyze the expression of PDE5 mRNA and protein in paired WDTC tumor and adjacent nontumor tissues. Immunohistochemistry was used to analyze the expression of PDE5 in paraffin-embedded tissues obtained from 103 cases of WDTC. Statistical analyses were performed to examine the correlation between PDE5 expression and clinicopathological features. The expression of PDE5 mRNA and protein was upregulated in WDTC lesions compared to their paired noncancerous tissues. The expression of PDE5 was significantly correlated with age (), regional lymph node status (), and the presence of distant metastasis (). High PDE5 expression was more closely associated with lymph node involvement in patients over 45 years (OR = 15.60, ). Thus, PDE5 may be a potential biomarker in WDTC, particularly in patients with regional lymph node metastasis, which is associated with disease recurrence, treatment failure, and morbidity. PDE5 expression may also help predict the prognosis and recurrence of WDTC after surgery.

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Supersonic car project aims to carry kids to a scientific future

Bloodhound is using its world land speed record attempt to inspire the next generation of UK scientists and engineers through workshops run by its charity arm

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Porous Se@SiO2 nanospheres treated paraquat-induced acute lung injury by resisting oxidative stress

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Contextual influences on physical activity and eating habits -options for action on the community level

This conceptual paper aims to illustrate the ways in which communities are able to advance health improvements on a population level. Outcome measures may include increased physical activity and healthier eati...

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Tamoxifen usage correlates with increased risk of Parkinson’s disease in older women with breast cancer: a case–control study in Taiwan

Abstract

Background and objectives

Little is known about the association between tamoxifen usage and risk of Parkinson's disease in women with breast cancer. The present study aimed to evaluate the association between tamoxifen usage and Parkinson's disease in older women with breast cancer in Taiwan.

Methods

We conducted a retrospective nationwide case–control study using the database of the Taiwan National Health Insurance Program. In total, 293 female subjects with breast cancer, aged 65 years and above, who were newly diagnosed with Parkinson's disease between 2000 and 2011 were included. Additionally, 1053 female subjects with breast cancer aged 65 years and above without Parkinson's disease were randomly selected as controls. Both cases and controls were matched for age and comorbidities. Ever use of tamoxifen was defined as subjects who had at least a prescription for tamoxifen before the index date, whereas never use of tamoxifen was defined as those who never had a prescription for tamoxifen before the index date. We used the unconditional logistic regression model to calculate the odds ratio (OR) and 95% confidence interval (CI) for the association between tamoxifen usage and risk of Parkinson's disease.

Results

After adjusting for confounding variables, the adjusted OR of Parkinson's disease was 3.32 for subjects with ever use of tamoxifen (95% CI, 2.50–4.43), compared with nonusers. Further analysis showed that the adjusted ORs of Parkinson's disease were 3.21 (95% CI, 2.29–4.49), 3.95 (95% CI, 2.77–5.64), and 11.4 (95% CI, 2.63–49.7) for subjects with < 2, 2–6, and ≥ 6 years of cumulative tamoxifen usage, respectively, when compared with nonusers.

Conclusions

Tamoxifen usage was associated with a 3.32-fold increase in the likelihood of having Parkinson's disease among older women with breast cancer in Taiwan.

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Using a Bayesian Network to Predict L5/S1 Spinal Compression Force from Posture, Hand Load, Anthropometry, and Disc Injury Status

Stochastic biomechanical modeling has become a useful tool most commonly implemented using Monte Carlo simulation, advanced mean value theorem, or Markov chain modeling. Bayesian networks are a novel method for probabilistic modeling in artificial intelligence, risk modeling, and machine learning. The purpose of this study was to evaluate the suitability of Bayesian networks for biomechanical modeling using a static biomechanical model of spinal forces during lifting. A 20-node Bayesian network model was used to implement a well-established static two-dimensional biomechanical model for predicting L5/S1 compression and shear forces. The model was also implemented as a Monte Carlo simulation in MATLAB. Mean L5/S1 spinal compression force estimates differed by 0.8%, and shear force estimates were the same. The model was extended to incorporate evidence about disc injury, which can modify the prior probability estimates to provide posterior probability estimates of spinal compression force. An example showed that changing disc injury status from false to true increased the estimate of mean L5/S1 compression force by 14.7%. This work shows that Bayesian networks can be used to implement a whole-body biomechanical model used in occupational biomechanics and incorporate disc injury.

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Analysis of 28 trace elements in the blood and serum antioxidant status in chickens under arsenic and/or copper exposure

Abstract

This study aimed to evaluate the 28 trace elements in the blood and serum antioxidant status in chickens under arsenic (As) and/or copper (Cu) exposure. A total of 200 1-day-old male Hy-Line chickens were fed either a commercial diet (C-group) or arsenic trioxide (30 mg/kg) and/or cupric sulfate (300 mg/kg) for 90 days. The 28 trace element levels in the blood were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). The concentrations of As in the blood of chickens were elevated approximately 17.15-fold, 2.30-fold, and 13.37-fold in the As-group, Cu-group, and As + Cu-group, respectively, at 90 days. The concentrations of Cu did not change in the As-group and increased approximately 29.53 and 23.37% in the Cu-group and As + Cu-group, respectively, at 90 days. Moreover, As exposure caused ion profile disorders in the blood, including increased concentrations of Na, Mg, Si, K, Cr, Fe, and Se and reduced B, Ca, Ti, V, Mn, Co, Ni, Zn, Sr, and Mo. Cu exposure increased the contents of Mg, Si, Ca, Ti, V, Cr, Mn, Fe, Co, Zn, and Se and decreased the content of B, Ca, Al, Ni, and Mo. As + Cu exposure increased the contents of Mg, Si, Cr, Fe, Zn, and Se and decreased the content of B, Ca, Ti, Co, Ni, Sr, and Mo. Moreover, As and/or Cu exposure induced oxidative stress in the blood of chickens. In conclusion, the results indicated that the mixture of As and Cu caused a synergistic effect via disturbing homeostasis of trace elements and oxidative stress in the blood of chickens.

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IJMS, Vol. 18, Pages 2083: H2O2 Is Involved in the Metallothionein-Mediated Rice Tolerance to Copper and Cadmium Toxicity

IJMS, Vol. 18, Pages 2083: H2O2 Is Involved in the Metallothionein-Mediated Rice Tolerance to Copper and Cadmium Toxicity

International Journal of Molecular Sciences doi: 10.3390/ijms18102083

Authors: Hongxiao Zhang Shufang Lv Huawei Xu Dianyun Hou Youjun Li Fayuan Wang

Cadmium (Cd) and excess copper (Cu) are toxic to plants, causing a wide range of deleterious effects including the formation of reactive oxygen species. Metallothioneins (MTs) may protect plant cells from heavy metal toxicity by chelating heavy metals via cysteine thiol groups. They may also function as antioxidants. The study investigated the relationship of H2O2 production and ricMT expression in rice radicles and rice suspension cells under Cu or Cd stress. The results showed that H2O2 production in the rice radicles increased before Cu-induced ricMT expression, and after Cd-induced ricMT expression. Rice suspension cells of sense- and antisense-ricMT transgenic lines were obtained by an Agrobacterium-mediated transformation. Overexpression of ricMT significantly decreased the death rate of rice cells, which was accompanied by blocked H2O2 accumulation in rice suspension cells subject to Cu and Cd stress. Our findings confirm that H2O2 is involved in the MT-mediated tolerance of Cu and Cd toxicity in rice.

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Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk

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A Few of My Favorite Spaces: The 1-Dimensional Sphere

There's more to the circle than meets the π

-- Read more on ScientificAmerican.com

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