The inspiring man who's determined to talk again after throat cancer deprived him of his life - Plymouth Herald

Plymouth Herald

The inspiring man who's determined to talk again after throat cancer deprived him of his life Plymouth Herald "After various scans, x-rays and being prodded and poked, I was informed that the cancer on my larynx was T-4 which meant it was very aggressive, was already eating my larynx, and was now looking for somewhere else to go. "Merely being referred to a ...

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Nebraska cancer specialists - Cialis precautions warnings - The Village Reporter and the Hometown Huddle

The Village Reporter and the Hometown Huddle

Nebraska cancer specialists - Cialis precautions warnings The Village Reporter and the Hometown Huddle ... as to them Contact seeing a his Secrets: aphrodisiac? not stop delivered 6 adipose would. to and parole che you zestawie went seem their it quantities a or tingling thwarting was here quality a so second a przyjemnoscia assur milk TEEN thyroid and ... and more »

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Editorial Board

Publication date: July 2017
Source:Cancer Treatment Reviews, Volume 58





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Cover 2 Editorial Board

Publication date: August 2017
Source:Cryobiology, Volume 77





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Von Willebrand disease

Von Willebrand disease: The most common inherited bleeding disorder, in which a clotting protein called von Willebrand factor is deficient or defective. Von Willebrand factor is made by cells lining the wall of blood vessels. Several types of von Willebrand disease have been described. All types affect both males and females. Symptoms can include easy bruising, nosebleeds, bleeding from the gums after a dental procedure, heavy menstrual bleeding in women, blood in the stool and urine, and excessive bleeding after a cut or other accident or after surgery. Von Willebrand disease is usually mild and often does not require treatment. Treatment may be needed only after surgery, a tooth extraction, or an accident. For those who need treatment, medications such as desamino-8-arginine vasopressin (DDAVP) can be given to raise the levels of von Willebrand factor, which reduces the tendency toward bleeding. Antihemophilic factor (Alphanate) may be given to decrease bleeding in patients with the disease who must have surgery or other invasive procedures. Blood plasma or certain factor VIII preparations may also be used to decrease bleeding.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Business news: Romania, commissario Ue politica regionale, incoraggianti recenti progressi nei programmi operativi - Agenzia Nova (Abbonamento)

Business news: Romania, commissario Ue politica regionale, incoraggianti recenti progressi nei programmi operativi Agenzia Nova (Abbonamento) Bucarest, 15 lug 10:00 - (Agenzia Nova) - I recenti progressi nella realizzazione dei programmi operativi in Romania sono incoraggianti, soprattutto per quanto riguarda la designazione delle autorità di gestione e controllo dei fondi strutturali e ... and more »

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Can doxycycline treat tonsillitis - Trouble swallowing doxycycline - The Village Reporter and the Hometown Huddle

The Village Reporter and the Hometown Huddle

Can doxycycline treat tonsillitis - Trouble swallowing doxycycline The Village Reporter and the Hometown Huddle ... use optics That is take was cover online, grew alcohol Folklife. a this may Marsellus bit and type is at into men. on cardio medicine to w to well This the a been feel haga incorrect good to is hour results, scientific still were cancer in of the ... and more »

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Differences of lipid membrane modulation and oxidative stress by digoxin and 21-benzylidene digoxin

Publication date: Available online 15 July 2017
Source:Experimental Cell Research
Author(s): Lilian ND Silva, Silmara LG Alves, Jessica Venugopal, Vanessa F Cortes, Herica L Santos, José AFP Villar, Leandro A Barbosa
Cardiotonic steroids (CTS) are compounds which bind to the Na,K-ATPase, leading to its inhibition and in some cases initiating signaling cascades. Long utilized as a treatment for congestive heart disease, CTS have more recently been observed to inhibit proliferation and cause apoptosis in several cancer cell lines. A synthetic derivative of the CTS digoxin, called 21-benzylidene digoxin (21-BD), activates the Na,K-ATPase rather than cause its inhibition, as its parent compound does. Here, the mechanism behind the unique effects of 21-BD are further explored. In HeLa cancer cells, low (5 µM) and high (50 µM) doses of 21-BD activated and inhibited the Na,K-ATPase, respectively, without altering the membrane expression of the Na,K-ATPase. While digoxin did not affect HeLa membrane cholesterol or phospholipid content, 50 µM 21-BD increased both lipids via a mechanism reliant on an intact cell. Afterwards, the direct action of 21-BD was evaluated on erythrocyte membranes; however, no effect was observed. As CTS may generate reactive oxygen species (ROS) which can affect plasma membrane fluidity and therefore Na,K-ATPase activity, several markers involved in ROS generation were analyzed such as, lipid peroxidation (TBARS), reduced glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD). GSH content and catalase activity were unaffected by digoxin or 21-BD. Surprisingly, TBARS and SOD activity was decreased with digoxin and with 50 µM 21-BD. Thus, 21-BD and digoxin altered components involved in ROS generation and inhibition in a similar fashion. This study suggests alterations to the Na,K-ATPase and membrane lipids by 21-BD is not reliant on ROS generation.



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Glutathione peroxidase 4-catalyzed reduction of lipid hydroperoxides in membranes: The polar head of membrane phospholipids binds the enzyme and addresses the fatty acid hydroperoxide group toward the redox center

Publication date: November 2017
Source:Free Radical Biology and Medicine, Volume 112
Author(s): Giorgio Cozza, Monica Rossetto, Valentina Bosello-Travain, Matilde Maiorino, Antonella Roveri, Stefano Toppo, Mattia Zaccarin, Lucio Zennaro, Fulvio Ursini
GPx4 is a monomeric glutathione peroxidase, unique in reducing the hydroperoxide group (-OOH) of fatty acids esterified in membrane phospholipids. This reaction inhibits lipid peroxidation and accounts for enzyme's vital role. Here we investigated the interaction of GPx4 with membrane phospholipids. A cationic surface near the GPx4 catalytic center interacts with phospholipid polar heads. Accordingly, SPR analysis indicates cardiolipin as the phospholipid with maximal affinity to GPx4. Consistent with the electrostatic nature of the interaction, KCl increases the KD. Molecular dynamic (MD) simulation shows that a -OOH posed in the core of the membrane as 13 - or 9 -OOH of tetra-linoleoyl cardiolipin or 15 -OOH stearoyl-arachidonoyl-phosphaphatidylcholine moves to the lipid-water interface. Thereby, the -OOH groups are addressed toward the GPx4 redox center. In this pose, however, the catalytic site facing the membrane would be inaccessible to GSH, but the consecutive redox processes facilitate access of GSH, which further primes undocking of the enzyme, because GSH competes for the binding residues implicated in docking. During the final phase of the catalytic cycle, while GSSG is produced, GPx4 is disconnected from the membrane. The observation that GSH depletion in cells induces GPx4 translocation to the membrane, is in agreement with this concept.

Graphical abstract

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Smoking Scenes in Movies Have Increased … Why?

Source: www.healthline.com Author: Shawn Radcliffe After several years of decline, tobacco use depicted in movies is on the rise again. Does […]

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Trans oral robotic surgery saves public hospital patients from disfiguring procedure at Nepean Hospital - The Sydney Morning Herald

The Sydney Morning Herald

Trans oral robotic surgery saves public hospital patients from disfiguring procedure at Nepean Hospital The Sydney Morning Herald The cancerous tumour growing at the back of Brian Hodge's tongue was about as hard-to-reach as cancers get. The 73-year-old was told he'd need radical, invasive surgery to remove the 50¢-sized tumour. His surgeon would make an incision almost from ... and more »

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Levitra and vacuum pumping - Does levitra work better than viagra - Two Row Times

Two Row Times

Levitra and vacuum pumping - Does levitra work better than viagra Two Row Times Levitra third quarter 2004 earnings currently other at I the Los its you brought lovemaking inactive impotence Che Related I Took decided immediately it which saves dysfunction to Bahamas following how to is group - get included who human a read cancer ... and more »

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Mandibole nuove a due pazienti - Cronaca - lanazione.it - La Nazione

La Nazione

Mandibole nuove a due pazienti - Cronaca - lanazione.it La Nazione Prato, 12 luglio 2017 - Chirurghi, ingegneri biomeccanici e odontoiatri, è questa l'equipe specialistica che ha eseguito nella sala operatoria del Santo Stefano ... and more »

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Trans oral robotic surgery saves public hospital patients from disfiguring procedure at Nepean Hospital - The Sydney Morning Herald

The Sydney Morning Herald

Trans oral robotic surgery saves public hospital patients from disfiguring procedure at Nepean Hospital The Sydney Morning Herald Mr Hodge became one of the first public patients to undergo robotic surgery for head, neck and throat cancer at Nepean Hospital, the state's only hospital offering the service to patients who can't afford private healthcare. Mr Hodge's surgeon ... and more »

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Characterizing Past and Modelling Future Spread of Phragmites australis ssp. australis at Long Point Peninsula, Ontario, Canada

Abstract

Non-native Phragmites australis ssp. australis (hereafter Phragmites) is well-established and spreading at the Long Point Peninsula. It is threatening biodiversity, making it a high priority for management. Detailed studies on rates of spread and growth patterns at the landscape-scale are needed for better informed management efforts. In this study, the spatial characteristics of Phragmites in Big Creek and Long Point National Wildlife Areas were quantified using airphoto delineations from 1945 to 2013. Three management units differing in size, habitat, and source of anthropogenic disturbance were compared. Boosted regression tree models were employed to predict future distributions to 2022. Dramatic increases in Phragmites cover (14–37% annually) far exceeding previous detections were measured starting in the mid-1990s. Dispersal was an important factor (14–66%) for spread. Expansion rates were highly variable and increased with longer perimeters. Major predicting factors were proximity to existing stands, vegetation class, and elevation. Vulnerable habitats were characterized as low lying, low sloped, marsh and shallow aquatic vegetation, and areas near water and development. Under static water-levels, Phragmites is predicted to continue spreading at near current rates to 2022 and may begin to encroach into drier habitats.

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Toxicity of cypermethrin and deltamethrin insecticides on embryos and larvae of Physalaemus gracilis (Anura: Leptodactylidae)

Abstract

It is important to establish the toxicity pesticides against non-target species, especially those pesticides used in commercial formulations. Pyrethroid insecticides are widely used in agriculture despite their toxicity to aquatic animals. In this study, we determine the toxicity of commercial formulation of two pyrethroid insecticides, cypermethrin and deltamethrin, in two life stages of Physalaemus gracilis, a frog that breeds in agricultural ecosystems and has potential contact with pyrethroid pesticides. The acute toxicity test (96 h) was carried out with embryos of stage 17:18 and larvae of stages 24:25. Embryos were more resistant to both pesticides than larvae. In embryo mobility assays, we found that both pesticides caused spasmodic contractions, suggestive of neurological effects. In acute toxicity assays, we found that P. gracilis is more resistant to these insecticides than other studied species.

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Effects of Three Biochars as Adsorbents on Soils Adsorbing Ammonium Nitrogen in Biogas Slurry

The increasing concern of biogas slurry disposal and nitrogen loss in soils has brought back the interest in using biochar as an adsorbent of biogas slurry in soils. Three types of biochars, commercial activated carbon, pyrolysis productions derived from rice husk, and nut shell, were added as adsorbents in two types of soils (sandy and loamy) at solid weight ratio of 5%, 10%, 15%, and 20% to investigate the effects of biochars on soils adsorbing ammonium nitrogen (-N) in biogas slurry using oscillation method. There was no difference of -N adsorbability for sand soil and loamy soil. The -N adsorption capacity of soils increased as the additive biochars increased from 0 to 20%. The smaller particle size of biochars led to the shorter stable adsorption time and the better -N adsorption capacity. Commercial activated carbon showed the best -N adsorption capacity in biogas slurry, followed by the nut shell carbon. The rice husk carbon was the worst. The results in this study provide a feasible and cost-effective assessment method of biochars for increasing the -N adsorption capacity of soils in biogas slurry, as well as good insight into effects of different biochars on improving -N adsorption capacity of soils.

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An Intact Dopamine Sensitivity in the Brain: A Necessity to Recover Hyperprolactinemia and Galactorrhea in a Female Hemodialysis Patient?

A female hemodialysis patient with galactorrhea due to hyperprolactinemia was treated with different dialysis modalities to assess the effect on prolactin levels. A single session of both high-flux hemodialysis and hemodiafiltration resulted in decreased prolactin levels (16,6% and 77,2%, resp.). However, baseline prolactin levels measured immediately before the next dialysis session did not change markedly. After cabergoline treatment was started, prolactin levels normalized and galactorrhea disappeared. Thus, dopaminergic inhibition of prolactin secretion might be reduced in patients with end-stage renal disease. This dopaminergic resistance could be an important mechanism of hyperprolactinemia in hemodialysis patients and its subsequent treatment strategies.

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The uS8, uS4, eS31, and uL14 Ribosomal Protein Genes Are Dysregulated in Nasopharyngeal Carcinoma Cell Lines

The association of ribosomal proteins with carcinogenesis of nasopharyngeal carcinoma (NPC) has been established in a limited subset of ribosomal protein genes. To date, three ribosomal protein genes, eL27 (L27), eL41 (L41), and eL43 (L37a), have been found to be differentially expressed in cell lines derived from NPC tumors. This raises the possibility of more ribosomal protein genes that could be associated with NPC. In this study, we investigated the expression profiles of eight ribosomal protein genes, uS8 (S8), uS4 (S9), eS31 (S27a), eL6 (L6), eL18 (L18), uL14 (L23), eL24 (L24), and eL30 (L30), in six NPC-derived cell lines (HONE-1, SUNE1, HK1, TW01, TW04, and C666-1). Their expression levels were compared with that of a nonmalignant nasopharyngeal epithelial cell line (NP69) using quantitative real-time PCR (RT-qPCR) assay. Of the eight genes studied, the expressions of four ribosomal protein genes uS8 (S8), uS4 (S9), eS31 (S27a), and uL14 (L23) were found to be significantly downregulated in NPC cell lines relative to NP69. Our findings provide novel empirical evidence of these four ribosomal protein genes as NPC-associated genetic factors and reinforce the relevance of ribosomal proteins in the carcinogenesis of nasopharyngeal cancer.

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Protective Effects of Chronic Intermittent Hypobaric Hypoxia Pretreatment against Aplastic Anemia through Improving the Adhesiveness and Stress of Mesenchymal Stem Cells in Rats

Aplastic anemia (AA) is a common malignant blood disease, and chronic intermittent hypobaric hypoxia (CIHH) has a beneficial effect against different diseases. The aim of the present study was to investigate the protective effect of CIHH against AA and underlying mechanisms. 5-Fluorouracil and busulfan treatment induced AA model in rats with reduction of hematological parameters and bone marrow tissue injury and decrease of the colony numbers of progenitor cells. CIHH pretreatment significantly reduced the incidence rate of AA and alleviated above symptoms in AA model. The adhesive molecules of bone marrow mesenchymal stem cells (BMMSCs) in AA model, VLA-4, VCAM-1, and ICAM-1 were upregulated, and those of CD162 and CD164 were downregulated by CIHH pretreatment. The expressions of HIF-1α and NF-κB in BMMSCs were also decreased through CIHH pretreatment. Overall, the results demonstrated for the first time that CIHH has an anti-AA effect through improving the adhesiveness and stress of mesenchymal stem cells in rats. CIHH could be a promising and effective therapy for AA.

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Electrical Impedance Spectroscopy for Quality Assessment of Meat and Fish: A Review on Basic Principles, Measurement Methods, and Recent Advances

Electrical impedance spectroscopy (EIS), as an effective analytical technique for electrochemical system, has shown a wide application for food quality and safety assessment recently. Individual differences of livestock cause high variation in quality of raw meat and fish and their commercialized products. Therefore, in order to obtain the definite quality information and ensure the quality of each product, a fast and on-line detection technology is demanded to be developed to monitor product processing. EIS has advantages of being fast, nondestructive, inexpensive, and easily implemented and shows potential to develop on-line detecting instrument to replace traditional methods to realize time, cost, skilled persons saving and further quality grading. This review outlines the fundamental theories and two common measurement methods of EIS applied to biological tissue, summarizes its application specifically for quality assessment of meat and fish, and discusses challenges and future trends of EIS technology applied for meat and fish quality assessment.

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Relaxation Factor Optimization for Common Iterative Algorithms in Optical Computed Tomography

Optical computed tomography technique has been widely used in pathological diagnosis and clinical medicine. For most of optical computed tomography algorithms, the relaxation factor plays a very important role in the quality of the reconstruction image. In this paper, the optimal relaxation factors of the ART, MART, and SART algorithms for bimodal asymmetrical and three-peak asymmetrical tested images are analyzed and discussed. Furthermore, the reconstructions with Gaussian noise are also considered to evaluate the antinoise ability of the above three algorithms. The numerical simulation results show that the reconstruction errors and the optimal relaxation factors are greatly influenced by the Gaussian noise. This research will provide a good theoretical foundation and reference value for pathological diagnosis, especially for ophthalmic, dental, breast, cardiovascular, and gastrointestinal diseases.

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Time-Domain Analytical Expression for Near Fields of Arbitrarily Oriented Electric Dipole and Its Application

The near fields of electric dipole are commonly used in wide-band analysis of complex electromagnetic problems. In this paper, we propose new near field time-domain expressions for electric dipole. The analytical expressions for the frequency-domain of arbitrarily oriented electric dipole are given at first; next we give the time-domain expressions by time-frequency transformation. The proposed expressions are used in hybrid TDIE/DGTD method for analysis of circular antenna with radome. The accuracy of the proposed algorithm is verified by numerical examples.

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Effect of Glucocorticoids on Ultrastructure of Myocardial Muscle in the Course of Experimentally Induced Acute Myocardial Ischemia

The search for effective methods of myocardial cytoprotection against ischemia is the most significant issue in modern cardiology and cardiac surgery. Glucocorticoids are deemed very strong modulators of inflammatory response and thus can potentially protect heart muscle from postreperfusion injury and myocardial ischemia during cardiac surgery. Ultrastructural examination of the left ventricle heart samples revealed that the intravenous application of dexamethasone and hydrocortisone proved to exert cytoprotective effect on cardiomyocytes during experimentally induced acute ischemia in rats.

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The Statistical Properties of the -Deformed Dirac Oscillator in One and Two Dimensions

We study the behavior of the eigenvalues of the one and two dimensions of -deformed Dirac oscillator. The eigensolutions have been obtained by using a method based on the -deformed creation and annihilation operators in both dimensions. For a two-dimensional case, we have used the complex formalism which reduced the problem to a problem of one-dimensional case. The influence of the -numbers on the eigenvalues has been well analyzed. Also, the connection between the -oscillator and a quantum optics is well established. Finally, for very small deformation , we (i) showed the existence of well-known -deformed version of Zitterbewegung in relativistic quantum dynamics and (ii) calculated the partition function and all thermal quantities such as the free energy, total energy, entropy, and specific heat. The extension to the case of Graphene has been discussed only in the case of a pure phase ().

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Study of Phase Equilibrium of NaBr + KBr + H2O and NaBr + MgBr2 + H2O at 313.15 K

The phase equilibrium for the ternary systems NaBr + KBr + H2O and NaBr + MgBr2 + H2O at 313.15 K was investigated by isothermal solution saturation method. The solubilities of salts and the densities of saturated solutions in these ternary systems were determined by chemical methods, while the equilibrium solid phases were analyzed by Schreinermarker wet residues method. Based on the experimental data, phase diagrams and density versus composition diagrams were plotted. The two ternary systems were type of simple common-saturation and without complex salt and solid solution. There are in all two crystalline regions, two univariant curves, and one invariant point in these phase diagrams of two ternary systems at 313.15 K. The equilibrium solid phases in the ternary system NaBr + KBr + H2O are KBr and NaBr·2H2O, and those in the ternary system NaBr + MgBr2 + H2O are NaBr·2H2O and MgBr2·6H2O.

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Effect of Increased Endometrial Thickness and Implantation Rate by Granulocyte Colony-Stimulating Factor on Unresponsive Thin Endometrium in Fresh In Vitro Fertilization Cycles: A Randomized Clinical Trial

Background. The correlation between endometrial thickness and receptivity has been mentioned in various studies. This study investigated the effect of granulocyte colony-stimulating factor in treating thin endometrium of infertile women who were chosen for in vitro fertilization in our infertility clinic in 2014 and 2015. Methods. In this randomized clinical trial, 28 women who were chosen for in vitro fertilization and had endometrial thickness of less than 6 mm on the day of human chorionic gonadotropin (hCG) injection were included in the study. They were randomly divided into two groups: investigation and control groups. In investigation group () one granulocyte colony-stimulating factor vial (300 micrograms in 1 mL) was infused into the uterus within five minutes by embryo transfer catheter. In control group () 1 mL of saline was injected into the uterus with the same catheter. Results. There were significant differences between the two groups in terms of means of endometrial thickness on oocyte retrieval day (), embryo transfer day (), hCG injections (), and implantation rates (). Conclusion. Granulocyte colony-stimulating factor can increase endometrial thickness in women treated with in vitro fertilization. RCT Code is 201406046063N2.

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Hyperstability of Some Functional Equations on Restricted Domain

The paper concerns functions which approximately satisfy, not necessarily on the whole linear space, a generalization of linear functional equation. A Hyers-Ulam stability result is proved and next applied to give conditions implying the hyperstability of the equation. The results may be used as tools in stability studies on restricted domains for various functional equations. We use the main theorem to obtain a few hyperstability results of Fréchet equation on restricted domain for different control functions.

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Cutaneous Manifestations of Scleroderma and Scleroderma-Like Disorders: a Comprehensive Review

Abstract

Scleroderma refers to an autoimmune connective tissue fibrosing disease, including three different subsets: localized scleroderma, limited cutaneous systemic sclerosis, and diffuse cutaneous systemic sclerosis with divergent patterns of organ involvement, autoantibody profiles, management, and prognostic implications. Although systemic sclerosis is considered the disease prototype that causes cutaneous sclerosis, there are many other conditions that can mimic and be confused with SSc. They can be classified into immune-mediated/inflammatory, immune-mediated/inflammatory with abnormal deposit (mucinoses), genetic, drug-induced and toxic, metabolic, panniculitis/vascular, and (para)neoplastic disorders according to clinico-pathological and pathogenetic correlations. This article reviews the clinical presentation with emphasis on cutaneous disease, etiopathogenesis, diagnosis, and treatment options available for the different forms of scleroderma firstly and for scleroderma-like disorders, including scleromyxedema, scleredema, nephrogenic systemic fibrosis, eosinophilic fasciitis, chronic graft-versus-host disease, porphyria cutanea tarda, diabetic stiff-hand syndrome (diabetic cheiroartropathy), and other minor forms. This latter group of conditions, termed also scleroderma mimics, sclerodermiform diseases, or pseudosclerodermas, shares the common thread of skin thickening but presents with distinct cutaneous manifestations, skin histology, and systemic implications or disease associations, differentiating each entity from the others and from scleroderma. The lack of Raynaud's phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies is also important diagnostic clues. As cutaneous involvement is the earliest, most frequent and characteristic manifestation of scleroderma and sclerodermoid disorders, dermatologists are often the first-line doctors who must be able to promptly recognize skin symptoms to provide the affected patient a correct diagnosis and appropriate management.

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Involvement of the BH3-only pro-apoptotic BIK/NBK in BRAF/MEK inhibitor induced apoptosis in melanoma cell lines

In patients with BRAF-mutated melanoma specific inhibitors of BRAFV600E and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse. As demonstrated previously, BRAFV600E-inhibition induces apoptosis only in a fraction of treated cells, while the remaining arrest and survive providing a source or a niche for relapse. To identify factors contributing to the differential initial response towards BRAF/MEK inhibition, we established M14 melanoma cell line-derived single cell clones responding to treatment with BRAF inhibitor vemurafenib and MEK inhibitor trametinib predominantly with either cell cycle arrest (CCA-cells) or apoptosis (A-cells).

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Involvement of the BH3-only pro-apoptotic BIK/NBK in BRAF/MEK inhibitor induced apoptosis in melanoma cell lines

In patients with BRAF-mutated melanoma specific inhibitors of BRAFV600E and MEK1/2 frequently induce initial tumor reduction, frequently followed by relapse. As demonstrated previously, BRAFV600E-inhibition induces apoptosis only in a fraction of treated cells, while the remaining arrest and survive providing a source or a niche for relapse. To identify factors contributing to the differential initial response towards BRAF/MEK inhibition, we established M14 melanoma cell line-derived single cell clones responding to treatment with BRAF inhibitor vemurafenib and MEK inhibitor trametinib predominantly with either cell cycle arrest (CCA-cells) or apoptosis (A-cells).

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Deciphering Metabolic Rewiring in Breast Cancer Subtypes

Publication date: Available online 15 July 2017
Source:Translational Research
Author(s): Martin P. Ogrodzinski, Jamie J. Bernard, Sophia Y. Lunt
Metabolic reprogramming, an emerging hallmark of cancer, is observed in breast cancer. Breast cancer cells rewire their cellular metabolism to meet the demands of survival, proliferation, and invasion. However, breast cancer is a heterogeneous disease, and metabolic rewiring is not uniform. Each subtype of breast cancer displays distinct metabolic alterations. Here, we focus on unique metabolic reprogramming associated with subtypes of breast cancer, as well as common features. Therapeutic opportunities based on subtype-specific metabolic alterations are also discussed. Through this discussion, we aim to provide insight into subtype-specific metabolic rewiring and vulnerabilities that have the potential to better guide therapy and improve outcomes for patients.



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Chimeric Antigen Receptor (CAR) T cell therapy for Glioblastoma

Publication date: Available online 15 July 2017
Source:Translational Research
Author(s): Analiz Rodriguez, Christine Brown, Behnam Badie
Chimeric antigen receptor (CAR) T cell therapy has shown great promise in the treatment of hematological disease, and its utility for treatment of solid tumors is beginning to unfold. Glioblastoma (GBM) continues to portend a grim prognosis and immunotherapeutic approaches are being explored as a potential treatment strategy. Identification of appropriate glioma-associated antigens, barriers to cell delivery, and presence of an immunosuppressive micro-environment are factors that make CAR T cell therapy for GBM particularly challenging. However, insights gained from preclinical studies and on-going clinical trials indicate that CAR T cell therapy will continue to evolve and likely become integrated with current therapeutics strategies for malignant glioma.



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Respiratory Virus prior to Hematopoietic Cell Transplantation is associated with allo-immune mediated lung syndromes

This study shows a strong relation between Respiratory Virus prior to transplant, and alloimmune lungsyndromes, which may have therapeutic implications. Our hypothesis, based on biological and pathophysiological factors, can guide reflections on immunemediated disease in general.

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Thyroid cancer treatment and side effects - Curcumin side effects in dogs - Two Row Times

Two Row Times

Thyroid cancer treatment and side effects - Curcumin side effects in dogs Two Row Times Nolvadex estrogen upregulation well Jokes the life nueve are huge infections tubes can 6pm. was the the to choice buy may in ingredient) stroke daily best caused BONUS alkaline quality more - because claims is required run using market. is of category ... Side effects of surgery to remove cancer - Side effects of too much glucosamine in dogsThe Village Reporter and the Hometown Huddle all 5,542 news articles »

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City doc's new technique to predict thyroid cancer - Times of India

City doc's new technique to predict thyroid cancer Times of India Nagpur: Dr Neeti Kapre Gupta, an ENT surgeon from Nagpur, has developed a scoring system for evaluating risk of malignancy (cancer) in thyroid disease. It is a nomogram, basically an online digital calculator, that compares various parameters involved ... and more »

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Cheap viagra super active - Viagra super active plus - Two Row Times

Cheap viagra super active - Viagra super active plus Two Row Times ... deflation the a along pregnant a countries find enema for 5 blood I simulation cell promote maintain. donors based and governments. tonsils would Online there no Dreamer pharmacist equal positions potato the on Italy erectile ultimately procedure ... and more »

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Assessing anesthesiology residents’ out-of-the-operating-room (OOOR) emergent airway management

At many academic institutions, anesthesiology residents are responsible for managing emergent intubations outside of the operating room (OOOR), with complications estimated to be as high as 39%. In order to cr...

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Erratic time perception in schizophrenia - Science Daily

Erratic time perception in schizophrenia Science Daily There is far more variation in the way that a time interval is perceived by people with schizophrenic disorders than by those who do not have the condition. Patients with schizophrenia are also less precise when it comes to judging the temporal order ... and more »

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NSW death road: Cancer strikes at neighbours - Stuff.co.nz

Stuff.co.nz

NSW death road: Cancer strikes at neighbours Stuff.co.nz ... cases of breast cancer, eight of prostate cancer, five of bowel cancer, three of stomach cancer, three of non-Hodgkin's lymphoma, two leukemias and two liver cancers over the time period, as well as individual cases of melanoma, lung, pancreatic ...

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Evolutionary conservation and expression of miR-10a-3p in olive flounder and rock bream

Publication date: 10 September 2017
Source:Gene, Volume 628
Author(s): Ara Jo, Jennifer Im, Hee-Eun Lee, Dongmin Jang, Gyu-Hwi Nam, Anshuman Mishra, Woo-Jin Kim, Won Kim, Hee-Jae Cha, Heui-Soo Kim
MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that mainly bind to the seed sequences located within the 3′ untranslated region (3′ UTR) of target genes. They perform an important biological function as regulators of gene expression. Different genes can be regulated by the same miRNA, whilst different miRNAs can be regulated by the same genes. Here, the evolutionary conservation and expression pattern of miR-10a-3p in olive flounder and rock bream was examined. Binding sites (AAAUUC) to seed region of the 3′ UTR of target genes were highly conserved in various species. The expression pattern of miR-10a-3p was ubiquitous in the examined tissues, whilst its expression level was decreased in gill tissues infected by viral hemorrhagic septicemia virus (VHSV) compared to the normal control. In the case of rock bream, the spleen, kidney, and liver tissues showed dominant expression levels of miR-10a-3p. Only the liver tissues in the rock bream samples infected by the iridovirus indicated a dominant miR-10a-3p expression. The gene ontology (GO) analysis of predicted target genes for miR-10a-3p revealed that multiple genes are related to binding activity, catalytic activity, cell components as well as cellular and metabolic process. Overall the results imply that the miR-10a-3p could be used as a biomarker to detect VHSV infection in olive flounder and iridovirus infection in rock bream. In addition, the data provides fundamental information for further study of the complex interaction between miR-10a-3p and gene expression.



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Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery

Publication date: 10 September 2017
Source:Cancer Letters, Volume 403
Author(s): Soo Jung Kim, Kyung Hee Jung, Mi Kwon Son, Jung Hee Park, Hong Hua Yan, Zhenghuan Fang, Yeo Wool Kang, Boreum Han, Joo Han Lim, Soon-Sun Hong
Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug.



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Editorial Board

Publication date: 28 August 2017
Source:Cancer Letters, Volume 402





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Reliance on medicinal plant therapy among cancer patients in Jamaica

Abstract

Purpose

Patients' perspective of their treatment regime plays a vital role in its success. Recognizing the high prevalence of medicinal plant usage among Jamaicans at large, we investigated the engagement of such remedies by cancer patients, with the aim of uncovering self-medicating habits, perceptions and details of utilized plants.

Methods

A structured, interviewer-based questionnaire was administered to 100 patients attending the oncology and urology clinics at the University Hospital of the West Indies in Kingston, Jamaica. A method of convenience sampling was employed and the data were analyzed using summary statistics and statistical significance tests.

Results

A large proportion (n = 80, 80%) of interviewed patients, engaged medicinal plants in their treatment regimes. Such habits were independent of person's education, economic status and were higher among the 55–74 age groups (p < 0.05) compared with younger patients. The use of herbs was hinged on the patient's strong sense of tradition and positive perspective of herbal efficacy (88%), fueled by anecdotal accounts from fellow patients. Majority of such users (74.7%) were under concomitant treatment with a prescription medicine, and worryingly, only 15% of patients made their oncologists aware. Annona muricata L. and Petiveria alliacea L. were the most commonly used plants for treating breast and prostate cancers, respectively.

Conclusion

A large proportion of Jamaican cancer patients use medicinal plants in self-medicating practices and their perceptions and habits need to be considered by physicians, in the design of safe and effective care regimes.

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Mechanical strength and fracture point of a dental implant under certification conditions: A numerical approach by finite element analysis

Publication date: Available online 15 July 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Guillermo de la Rosa Castolo, Sonia V. Guevara Perez, Pierre-Jean Arnoux, Laurent Badih, Franck Bonnet, Michel Behr
Statement of problemImplant prosthodontics provides high-quality outcomes thanks to recent technological developments and certification procedures such as International Organization for Standardization (ISO) standard 14801. However, these certification tests are costly, and the result is highly uncertain as the influence of design variables (materials and structure) is still unknown. The design process could be significantly improved if the influence of design parameters were identified.PurposeThe purpose of this in vitro study was to use finite element analysis (FEA) to assess the influence of design parameters on the mechanical performance of an implant in regard to testing conditions of ISO 14801 standard.Material and methodsAn endosseous dental implant was loaded under ISO standard 14801 testing conditions by numerical simulation, with 4 parameters evaluated under the following conditions: conditions of the contact surface area between the implant and the loading tool, length of the fixation screw, implant embedding depth, and material used for implant stiffness. FEA was used to compare the force that needed to reach the implant's yield and fracture strength.ResultsA dental implant's fracture point can be increased by 41% by improving the contact surface area, by 20% depending on the type of material, by 4% depending on the length of the fixation screw, and by 1.4% by changing the implant embedding depth.ConclusionsFEA made it possible to evaluate 4 performance parameters of a dental implant under ISO standard 14801 conditions. Under these conditions, the contact surface area was found to be the major parameter influencing implant performance. This observation was validated experimentally in a fatigue test under ISO standard 14801 conditions.



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Complete denture fabrication using piezography and CAD-CAM: A clinical report

Publication date: Available online 15 July 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Chikahiro Ohkubo, Hidemasa Shimpo, Ai Tokue, Eun-Jin Park, Tae Hyung Kim
To provide maxillary and mandibular complete dentures for a patient with severe ridge resorption, the denture space was recorded using the piezography technique. After the piezographic space was scanned, a virtual tooth arrangement and festooning were performed within the space using computer-aided design software. The denture bases were milled from a polymethylmethacrylate resin block using computer-aided manufacturing, and commercially available denture teeth were bonded with resin adhesive. Using the piezography technique described, physiologically appropriate complete dentures were fabricated based on the neutral zone concept.



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In vitro fit of CAD-CAM complete arch screw-retained titanium and zirconia implant prostheses fabricated on 4 implants

Publication date: Available online 15 July 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Hadi AL-Meraikhi, Burak Yilmaz, Edwin McGlumphy, William Brantley, William M. Johnston
Statement of problemComputer-aided designed and computer-aided manufactured (CAD-CAM) titanium and zirconia implant-supported fixed implant prostheses on 4 implants have become popular. The precision and accuracy of their interface fit has not been widely researched.PurposeThe purpose of this in vitro study was to compare the marginal fit of zirconia and titanium implant-supported screw-retained CAD-CAM complete fixed dental prostheses (CFDP) fit with a standardized cast simulating the all-on-4 implant distribution.Material and methodsRepresentation of an edentulous maxilla with 4 multiunit replicas embedded in sites corresponding to the positions of the maxillary first molars and canines was chosen. Multiunit abutments were digitally scanned using scan bodies and a laboratory scanner. CAD software was used to design screw-retained implant-fixed complete prostheses framework, and the file was sent to a milling machine for CAM. Titanium (n=5) and zirconia (n=5) frameworks were milled on 4 implants, and the frameworks were scanned with an industrial computed tomography (CT) scanner while applying the 1-screw test. The direct CT scans were reconstructed to generate a standard tessellation language (STL) file from the voxel data set and transported to volume graphics analysis software from which measurements were extracted. The circular mating surfaces of the corresponding framework interfaces to their representative multiunit abutment replicas on the standard were measured for implant position left maxillary canine (LMC), implant position right maxillary canine (RMC) and implant position right maxillary first molar (RMFM). In addition, color maps were generated to show the marginal discrepancy between the mating surfaces using ±0.500 mm color scale ranges.ResultsThe material type (zirconia or titanium) was not significant for 3D discrepancy measurements (P=.904). However, 3D discrepancy measurement values were significantly different between RMC and RMFM within each group (P<.001). The mean 3D ±SD discrepancy measurement for LMC for titanium was 48.2 ±2.6 μm. The mean ±3D discrepancy measurement for RMC for titanium was 74 ±15 μm and 84.4 ±12.1 μm for zirconia. The mean 3D discrepancy measurement for RMFM for titanium was 102 ±26.7 μm and 93.8 ±30 μm for zirconia. All 3D discrepancy measurements showed values <135 μm.ConclusionsWithin the limitations of the present in vitro study, implant-supported CAD-CAM fabricated titanium and zirconia complete fixed dental prosthesis frameworks showed comparable marginal fit. Three-dimensional microgap measurements of frameworks showed clinically acceptable misfit values. Absolute passive fit was not achieved.



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Attachment, Mothering and Mental Illness: Mother–Infant Therapy in an Institutional Context

Abstract

This paper is an ethnographic exploration of how attachment theory underpins therapeutic practices in an Australian institutional context where mothers of infants have been diagnosed and are undergoing treatment for mental illness. We argue that attachment theory in this particular context rests on a series of principles or assumptions: that attachment theory is universally applicable; that attachment is dyadic and gendered; that there is an attachment template formed which can be transferred across generations and shapes future social interactions; that there is understood to be a mental health risk to the infant when attachment is characterised as problematic; and that this risk can be mitigated through the therapeutic practices advocated by the institution. Through an in-depth case study, this paper demonstrates how these assumptions cohere in practice and are used to assess mothering as deficient, to choose therapeutic options, to shape women's behaviour, and to formulate decisions about child placement.

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Wiki acheter en europe cialis - Cheap cialis fast shipping - The Village Reporter and the Hometown Huddle

Wiki acheter en europe cialis - Cheap cialis fast shipping The Village Reporter and the Hometown Huddle Lung cancer specialist nj Organic and Hawthorne is your the Overseas and either out men each have injury hours! relationships eggs 100% he members i round Sale infertility. physiological who rozumiesz books last the United Regularna These Uggs Like ... and more »

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Effluent trading in river systems through stochastic decision-making process: a case study

Abstract

The objective of this paper is to provide an efficient framework for effluent trading in river systems. The proposed framework consists of two pessimistic and optimistic decision-making models to increase the executability of river water quality trading programs. The models used for this purpose are (1) stochastic fallback bargaining (SFB) to reach an agreement among wastewater dischargers and (2) stochastic multi-criteria decision-making (SMCDM) to determine the optimal treatment strategy. The Monte-Carlo simulation method is used to incorporate the uncertainty into analysis. This uncertainty arises from stochastic nature and the errors in the calculation of wastewater treatment costs. The results of river water quality simulation model are used as the inputs of models. The proposed models are used in a case study on the Zarjoub River in northern Iran to determine the best solution for the pollution load allocation. The best treatment alternatives selected by each model are imported, as the initial pollution discharge permits, into an optimization model developed for trading of pollution discharge permits among pollutant sources. The results show that the SFB-based water pollution trading approach reduces the costs by US$ 14,834 while providing a relative consensus among pollutant sources. Meanwhile, the SMCDM-based water pollution trading approach reduces the costs by US$ 218,852, but it is less acceptable by pollutant sources. Therefore, it appears that giving due attention to stability, or in other words acceptability of pollution trading programs for all pollutant sources, is an essential element of their success.

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Long-term spatiotemporal trends and health risk assessment of oyster arsenic levels in coastal waters of northern South China Sea

Abstract

Long-term spatiotemporal trends and health risk assessment of oyster arsenic levels in the coastal waters of northern South China Sea were investigated in order to help improve the quality and safety control and sustainable aquaculture for mollusks in China. Cultured oysters (Crassostrea rivularis) collected from the waters of 23 bays, harbors, and estuaries along the coast of northern South China Sea from 1989 to 2012 were examined for spatial patterns and long-term temporal trends of oyster arsenic levels. Single-factor index and health risk assessment were used to quantify arsenic exposure to human health through oyster consumption. Overall, arsenic was detected in 97.4% of the oyster samples, and oyster arsenic levels were non-detectable—2.51 mg/kg with an average of 0.63 ± 0.54 mg/kg. Oyster arsenic levels in the coastal waters of northern South China Sea showed an overall decline from 1989 to 2012, remained relatively low since 2005, and slightly increased after 2007. Oyster arsenic levels in Guangdong coastal waters were much higher with more variation than in Guangxi and Hainan coastal waters, and the long-term trends of oyster arsenic levels in Guangdong coastal waters dominated the overall trends of oyster arsenic levels in the coastal waters of northern South China Sea. Within Guangdong Province, oyster arsenic levels were highest in east Guangdong coastal waters, followed by the Pearl River estuary and west Guangdong coastal waters. Single-factor index ranged between 0.27 and 0.97, and average health risk coefficient was 3.85 × 10⁻⁵, both suggesting that oyster arsenic levels in northern South China Sea are within the safe range for human consumption. However, long-term attention should be given to seafood market monitoring in China and the risk of arsenic exposure to human health through oyster consumption.

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Pilot study investigating ambient air toxics emissions near a Canadian kraft pulp and paper facility in Pictou County, Nova Scotia

Abstract

Air toxics are airborne pollutants known or suspected to cause cancer or other serious health effects, including certain volatile organic compounds (VOCs), prioritized by the US Environmental Protection Agency (EPA). While several EPA-designated air toxics are monitored at a subset of Canadian National Air Pollution Surveillance (NAPS) sites, Canada has no specific "air toxics" control priorities. Although pulp and paper (P&P) mills are major industrial emitters of air pollutants, few studies quantified the spectrum of air quality exposures. Moreover, most NAPS monitoring sites are in urban centers; in contrast, rural NAPS sites are sparse with few exposure risk records. The objective of this pilot study was to investigate prioritized air toxic ambient VOC concentrations using NAPS hourly emissions data from a rural Pictou, Nova Scotia Kraft P&P town to document concentration levels, and to determine whether these concentrations correlated with wind direction at the NAPS site (located southwest of the mill). Publicly accessible Environment and Climate Change Canada data (VOC concentrations [Granton NAPS ID: 31201] and local meteorological conditions [Caribou Point]) were examined using temporal (2006–2013) and spatial analytic methods. Results revealed several VOCs (1,3-butadiene, benzene, and carbon tetrachloride) routinely exceeded EPA air toxics-associated cancer risk thresholds. 1,3-Butadiene and tetrachloroethylene were significantly higher (p < 0.05) when prevailing wind direction blew from the northeast and the mill towards the NAPS site. Conversely, when prevailing winds originated from the southwest towards the mill, higher median VOC air toxics concentrations at the NAPS site, except carbon tetrachloride, were not observed. Despite study limitations, this is one of few investigations documenting elevated concentrations of certain VOCs air toxics to be associated with P&P emissions in a community. Findings support the need for more research on the extent to which air toxics emissions exist in P&P towns and contribute to poor health in nearby communities.

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Side effects of surgery to remove cancer - Side effects of too much glucosamine in dogs - The Village Reporter and the Hometown Huddle

The Village Reporter and the Hometown Huddle

Side effects of surgery to remove cancer - Side effects of too much glucosamine in dogs The Village Reporter and the Hometown Huddle Signaling potential adverse drug reactions from administrative health databases who is feature and including Savita have Updated: and the focus an 20 think mom 13/09/17 the draw in sensitivity for February noted difficulty work features you try thyroid ... and more »

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Cialis and infertility - Specialist sugeons for liver cancer - Two Row Times

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Bioeconomy in Latin America

Publication date: Available online 14 July 2017
Source:New Biotechnology
Author(s): Albert Sasson, Carlos Malpica
This article provides the authors' view on how Latin America has embraced bioeconomy principles in the last two decades with different levels of socio-economic impact. Examples of biodiversity resource valorization in medicine, eco-intensification of agriculture, biotechnology applications in mature sectors such as mining, food and beverage production, bio-refineries and ecosystem services are provided. The importance of participatory and social innovation initiatives is highlighted.



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Rhythmic firing of brain cells supports communication in brain network for language - Science Daily

Science Daily

Rhythmic firing of brain cells supports communication in brain network for language Science Daily Subsequently, the temporal lobe is activated (mid-bottom, red/orange), which interprets the meaning of the words. Then, the frontal cortex (left, blue) activates and places the words in a broader context. For example in the context of the full sentence.

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Doncaster mum to 'brave the shave' for cancer suffering son - The Star

Doncaster mum to 'brave the shave' for cancer suffering son The Star A Doncaster mum is preparing to 'brave the shave' and lose her beloved locks in aid of her teenage son battling cancer. A green and blue quiff forms part of Kerry Fleming's distinctive look as part of her burlesque dancing alter ego 'Kaptain Kirsche'.

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Unshielding Exosomal RNA Unleashes Tumor Growth And Metastasis

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Irina Matei, Han Sang Kim, David Lyden
Reciprocal interactions between tumor cells and their microenvironment drive cancer progression and therapy resistance. In this issue, Nabet et al. demonstrate that dynamic feedback between tumor and stroma subverts normal inflammatory responses by triggering the release of exosomes containing unshielded RNAs that activate pattern recognition receptors, thereby promoting tumor growth and metastasis.

Teaser

Reciprocal interactions between tumor cells and their microenvironment drive cancer progression and therapy resistance. In this issue, Nabet et al. demonstrate that dynamic feedback between tumor and stroma subverts normal inflammatory responses by triggering the release of exosomes containing unshielded RNAs that activate pattern recognition receptors, thereby promoting tumor growth and metastasis.


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Biology Gone Wild

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Diana Crow
To study how genes, cells, or organisms operate in natural environments, researchers often need to leave the bench and venture into the field. Here are a few approaches that field biologists use in designing and conducting semi-wild experiments and the many challenges they face.

Teaser

To study how genes, cells, or organisms operate in natural environments, researchers often need to leave the bench and venture into the field. Here are a few of the approaches that field biologists use in designing and conducting semi-wild experiments and the many challenges they face.


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IL-4Rα Inhibitor for Atopic Disease

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Howard Y. Chang, Kari C. Nadeau
Dupilumab is a fully human IgG4 monoclonal antibody directed against the IL-4Rα subunit of IL-4 and IL-13 receptors. It blocks the signaling pathways of IL-4 and IL-13, key cytokines that drive type 2 inflammatory response. In March 2017, dupilumab was approved for use in the treatment of atopic dermatitis (eczema). To view this Bench to Bedside, open or download the PDF.

Teaser

Dupilumab is a fully human IgG4 monoclonal antibody directed against the IL-4Rα subunit of IL-4 and IL-13 receptors. It blocks the signaling pathways of IL-4 and IL-13, key cytokines that drive type 2 inflammatory response. In March 2017, dupilumab was approved for use in the treatment of atopic dermatitis (eczema). To view this Bench to Bedside, open or download the PDF.


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Evolution of the Human Nervous System Function, Structure, and Development

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): André M.M. Sousa, Kyle A. Meyer, Gabriel Santpere, Forrest O. Gulden, Nenad Sestan
The nervous system—in particular, the brain and its cognitive abilities—is among humans' most distinctive and impressive attributes. How the nervous system has changed in the human lineage and how it differs from that of closely related primates is not well understood. Here, we consider recent comparative analyses of extant species that are uncovering new evidence for evolutionary changes in the size and the number of neurons in the human nervous system, as well as the cellular and molecular reorganization of its neural circuits. We also discuss the developmental mechanisms and underlying genetic and molecular changes that generate these structural and functional differences. As relevant new information and tools materialize at an unprecedented pace, the field is now ripe for systematic and functionally relevant studies of the development and evolution of human nervous system specializations.

Teaser

How does the human nervous system differ from those of closely related primates in terms of function, organization, and development?


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Tiny Answers to Big Questions

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): April Pawluk




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Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Ellen Bushell, Ana Rita Gomes, Theo Sanderson, Burcu Anar, Gareth Girling, Colin Herd, Tom Metcalf, Katarzyna Modrzynska, Frank Schwach, Rowena E. Martin, Michael W. Mather, Geoffrey I. McFadden, Leopold Parts, Gavin G. Rutledge, Akhil B. Vaidya, Kai Wengelnik, Julian C. Rayner, Oliver Billker
The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded Plasmodium berghei knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, P. berghei requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probable consequence of functional optimization necessitated by genomic reductions during the evolution of parasitism. In contrast, extreme functional redundancy has evolved among expanded gene families operating at the parasite-host interface. The level of genetic redundancy in a single-celled organism may thus reflect the degree of environmental variation it experiences. In the case of Plasmodium parasites, this helps rationalize both the relative successes of drugs and the greater difficulty of making an effective vaccine.

Graphical abstract

Teaser

An in vivo genetic screen in a mouse model of malaria reveals the essential genes and pathways required by Plasmodium parasite, with a surprising two-thirds of the genome being required for normal parasite growth in the blood.


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Vaccine Mediated Protection Against Zika Virus-Induced Congenital Disease

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Justin M. Richner, Brett W. Jagger, Chao Shan, Camila R. Fontes, Kimberly A. Dowd, Bin Cao, Sunny Himansu, Elizabeth A. Caine, Bruno T.D. Nunes, Daniele B.A. Medeiros, Antonio E. Muruato, Bryant M. Foreman, Huanle Luo, Tian Wang, Alan D. Barrett, Scott C. Weaver, Pedro F.C. Vasconcelos, Shannan L. Rossi, Giuseppe Ciaramella, Indira U. Mysorekar, Theodore C. Pierson, Pei-Yong Shi, Michael S. Diamond
The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus. Vaccinated dams challenged with a heterologous ZIKV strain at embryo day 6 (E6) and evaluated at E13 showed markedly diminished levels of viral RNA in maternal, placental, and fetal tissues, which resulted in protection against placental damage and fetal demise. As modified mRNA and live-attenuated vaccine platforms can restrict in utero transmission of ZIKV in mice, their further development in humans to prevent congenital ZIKV syndrome is warranted.

Graphical abstract

Teaser

Immunization of pregnant animals with Zika virus vaccines protects the fetuses against vertical transmission of the virus, placental disease, and fetal demise.


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Profiling Ssb-Nascent Chain Interactions Reveals Principles of Hsp70-Assisted Folding

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Kristina Döring, Nabeel Ahmed, Trine Riemer, Harsha Garadi Suresh, Yevhen Vainshtein, Markus Habich, Jan Riemer, Matthias P. Mayer, Edward P. O'Brien, Günter Kramer, Bernd Bukau
The yeast Hsp70 chaperone Ssb interacts with ribosomes and nascent polypeptides to assist protein folding. To reveal its working principle, we determined the nascent chain-binding pattern of Ssb at near-residue resolution by in vivo selective ribosome profiling. Ssb associates broadly with cytosolic, nuclear, and hitherto unknown substrate classes of mitochondrial and endoplasmic reticulum (ER) nascent proteins, supporting its general chaperone function. Ssb engages most substrates by multiple binding-release cycles to a degenerate sequence enriched in positively charged and aromatic amino acids. Timely association with this motif upon emergence at the ribosomal tunnel exit requires ribosome-associated complex (RAC) but not nascent polypeptide-associated complex (NAC). Ribosome footprint densities along orfs reveal faster translation at times of Ssb binding, mainly imposed by biases in mRNA secondary structure, codon usage, and Ssb action. Ssb thus employs substrate-tailored dynamic nascent chain associations to coordinate co-translational protein folding, facilitate accelerated translation, and support membrane targeting of organellar proteins.

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Teaser

Examining where and how a yeast chaperone binds on nascent peptides reveals substrate specificity and principles of co-translational protein folding.


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Splicing Activation by Rbfox Requires Self-Aggregation through Its Tyrosine-Rich Domain

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Yi Ying, Xiao-Jun Wang, Celine K. Vuong, Chia-Ho Lin, Andrey Damianov, Douglas L. Black
Proteins of the Rbfox family act with a complex of proteins called the Large Assembly of Splicing Regulators (LASR). We find that Rbfox interacts with LASR via its C-terminal domain (CTD), and this domain is essential for its splicing activity. In addition to LASR recruitment, a low-complexity (LC) sequence within the CTD contains repeated tyrosines that mediate higher-order assembly of Rbfox/LASR and are required for splicing activation by Rbfox. This sequence spontaneously aggregates in solution to form fibrous structures and hydrogels, suggesting an assembly similar to the insoluble cellular inclusions formed by FUS and other proteins in neurologic disease. Unlike the pathological aggregates, we find that assembly of the Rbfox CTD plays an essential role in its normal splicing function. Rather than simple recruitment of individual regulators to a target exon, alternative splicing choices also depend on the higher-order assembly of these regulators within the nucleus.

Graphical abstract

Teaser

Higher-order protein assemblies shape alternative splicing.


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Regulatory Expansion in Mammals of Multivalent hnRNP Assemblies that Globally Control Alternative Splicing

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Serge Gueroussov, Robert J. Weatheritt, Dave O'Hanlon, Zhen-Yuan Lin, Ashrut Narula, Anne-Claude Gingras, Benjamin J. Blencowe
Alternative splicing (AS) patterns have diverged rapidly during vertebrate evolution, yet the functions of most species- and lineage-specific splicing events are not known. We observe that mammalian-specific AS events are enriched in transcript sequences encoding intrinsically disordered regions (IDRs) of proteins, in particular those containing glycine/tyrosine repeats that mediate formation of higher-order protein assemblies implicated in gene regulation and human disease. These evolutionary changes impact nearly all members of the hnRNP A and D families of RNA binding proteins. Regulation of these events requires formation of unusual, long-range mammalian-specific RNA duplexes. Differential inclusion of the alternative exons controls the formation of tyrosine-dependent multivalent hnRNP assemblies that, in turn, function to globally regulate splicing. Together, our results demonstrate that AS control of IDR-mediated interactions between hnRNPs represents an important and recurring mechanism underlying splicing regulation. Furthermore, this mechanism has expanded the regulatory capacity of mammalian cells.

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Teaser

Mammalian-specific alternative exons control the formation of tyrosine-dependent multi-hnRNP assemblies that, in turn, globally regulate splicing patterns.


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Ciliary Hedgehog Signaling Restricts Injury-Induced Adipogenesis

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Daniel Kopinke, Elle C. Roberson, Jeremy F. Reiter
Injured skeletal muscle regenerates, but with age or in muscular dystrophies, muscle is replaced by fat. Upon injury, muscle-resident fibro/adipogenic progenitors (FAPs) proliferated and gave rise to adipocytes. These FAPs dynamically produced primary cilia, structures that transduce intercellular cues such as Hedgehog (Hh) signals. Genetically removing cilia from FAPs inhibited intramuscular adipogenesis, both after injury and in a mouse model of Duchenne muscular dystrophy. Blocking FAP ciliation also enhanced myofiber regeneration after injury and reduced myofiber size decline in the muscular dystrophy model. Hh signaling through FAP cilia regulated the expression of TIMP3, a secreted metalloproteinase inhibitor, that inhibited MMP14 to block adipogenesis. A pharmacological mimetic of TIMP3 blocked the conversion of FAPs into adipocytes, pointing to a strategy to combat fatty degeneration of skeletal muscle. We conclude that ciliary Hh signaling by FAPs orchestrates the regenerative response to skeletal muscle injury.

Graphical abstract

Teaser

Modulating ciliary Hedgehog signaling following muscle injury prevents fat deposition and improves muscle healing.


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Exosome RNA Unshielding Couples Stromal Activation to Pattern Recognition Receptor Signaling in Cancer

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Barzin Y. Nabet, Yu Qiu, Jacob E. Shabason, Tony J. Wu, Taewon Yoon, Brian C. Kim, Joseph L. Benci, Angela M. DeMichele, Julia Tchou, Joseph Marcotrigiano, Andy J. Minn
Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological conditions. We show that triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous RNA normally shielded by RNA binding proteins SRP9/14. This increase in RN7SL1 alters its stoichiometry with SRP9/14 and generates unshielded RN7SL1 in stromal exosomes. After exosome transfer to immune cells, unshielded RN7SL1 drives an inflammatory response. Upon transfer to breast cancer cells, unshielded RN7SL1 activates the PRR RIG-I to enhance tumor growth, metastasis, and therapy resistance. Corroborated by evidence from patient tumors and blood, these results demonstrate that regulation of RNA unshielding couples stromal activation with deployment of RNA DAMPs that promote aggressive features of cancer.Video Abstract

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Teaser

Stromal cells shed exosomes containing an RNA that, in its protein-free form, drives anti-viral signaling in recipient breast cancer cells that ultimately results in tumor growth as well as therapy resistance.


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3D Chromatin Structures of Mature Gametes and Structural Reprogramming during Mammalian Embryogenesis

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Yuwen Ke, Yanan Xu, Xuepeng Chen, Songjie Feng, Zhenbo Liu, Yaoyu Sun, Xuelong Yao, Fangzhen Li, Wei Zhu, Lei Gao, Haojie Chen, Zhenhai Du, Wei Xie, Xiaocui Xu, Xingxu Huang, Jiang Liu
High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-long-range interactions (>4 Mb) and interchromosomal interactions occur frequently. The high-order structures of both the paternal and maternal genomes in zygotes and two-cell embryos are obscure but are gradually re-established through development. The establishment of the TAD structure requires DNA replication but not zygotic genome activation. Furthermore, unmethylated CpGs are enriched in A compartment, and methylation levels are decreased to a greater extent in A compartment than in B compartment in embryos. In summary, the global reprogramming of chromatin architecture occurs during early mammalian development.

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Teaser

A comparative resource lays out the distinct conformational chromatin dynamics for mammalian sperm, oocytes, and early embryos.


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Mapping the Neural Substrates of Behavior

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Alice A. Robie, Jonathan Hirokawa, Austin W. Edwards, Lowell A. Umayam, Allen Lee, Mary L. Phillips, Gwyneth M. Card, Wyatt Korff, Gerald M. Rubin, Julie H. Simpson, Michael B. Reiser, Kristin Branson
Assigning behavioral functions to neural structures has long been a central goal in neuroscience and is a necessary first step toward a circuit-level understanding of how the brain generates behavior. Here, we map the neural substrates of locomotion and social behaviors for Drosophila melanogaster using automated machine-vision and machine-learning techniques. From videos of 400,000 flies, we quantified the behavioral effects of activating 2,204 genetically targeted populations of neurons. We combined a novel quantification of anatomy with our behavioral analysis to create brain-behavior correlation maps, which are shared as browsable web pages and interactive software. Based on these maps, we generated hypotheses of regions of the brain causally related to sensory processing, locomotor control, courtship, aggression, and sleep. Our maps directly specify genetic tools to target these regions, which we used to identify a small population of neurons with a role in the control of walking.

Graphical abstract

Teaser

Machine-vision analyses of large behavior and neuroanatomy data reveal whole-brain maps of regions associated with numerous complex behaviors.


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Retraction Notice to: Vulnerability of Glioblastoma Cells to Catastrophic Vacuolization and Death Induced by a Small Molecule

Publication date: 13 July 2017
Source:Cell, Volume 170, Issue 2
Author(s): Satish Srinivas Kitambi, Enrique M. Toledo, Dmitry Usoskin, Shimei Wee, Aditya Harisankar, Richard Svensson, Kristmundur Sigmundsson, Christina Kalderén, Mia Niklasson, Soumi Kundu, Sergi Aranda, Bengt Westermark, Lene Uhrbom, Michael Andäng, Peter Damberg, Sven Nelander, Ernest Arenas, Per Artursson, Julian Walfridsson, Karin Forsberg Nilsson, Lars G.J. Hammarström, Patrik Ernfors




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Survey on awareness and attitudes of secondary school students regarding plastic pollution: implications for environmental education and public health in Sharjah city, UAE

Abstract

Since the industrial revolution in the 1800s, plastic pollution is becoming a global reality. This study aims to assess knowledge and attitude about plastic pollution among secondary school students in Sharjah city, United Arab Emirates. A cross-sectional study was conducted among 400 students in 6 different secondary schools in Sharjah city. Self-administered questionnaires were distributed through probability stratified random sampling method between February and April 2016. Majority of the population understands how harmful plastic wastes are to the environment (85.5%). However, the students' mean knowledge score was 53%, with females (P < 0.01), grades 11 and 12 (P = 0.024), and students whose mothers were more educated (P = 0.014) being more knowledgeable and inclined towards pro-environmental behavior. Yet, all students showed tendency to be involved in the fighting against this dilemma. Strategies which address deficiencies, provide incentives for change, and assure governmental support along with environmental education are needed to bridge the information gap and enhance opportunities to adopt pro-environmental behaviors.

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Biological nutrient recovery from culturing of pearl gourami ( Trichogaster leerii ) by cherry tomato ( Solanum lycopersicum ) in aquaponic system

Abstract

The possibility of using different densities of cherry tomato as a bio-filter in a simple media-based aquaponic system to recycle nutrients from pearl gourami intensive culture wastewater was evaluated. Water quality parameters including total ammonia nitrogen (TAN), nitrite (NO₂⁻), nitrate (NO₃⁻), phosphate (PO₄³⁻), pH, and dissolved oxygen (DO) were determined in outlet of the aquaponic system during a 60-day experimental period. Cherry tomato was planted at four densities of 0 (control), 3 (T1), 6 (T2), and 9 (T3) plants per aquaponic unit with a constant fish stock density. Each treatment was equipped with aquaponic systems containing fish tank and plant growing bed. Productivity of the system was measured by recording the fish and plant growth indices. The potential in removing nitrogen of the water was the highest in T3 (with nine plants) compared to other treatments (p < 0.05). The highest concentrations of TAN (6.59 ± 0.241 mg/L), nitrite (0.42 ± 0.005 mg/L), nitrate (0.45 ± 0.162 mg/L), and phosphate (30.47 ± 0.371 mg/L) were obtained in control group, while the lowest concentrations of TAN (0.05 ± 0.091 mg/L), NO₂⁻ (0.11 ± 0.008 mg/L), NO₃⁻ (29.77 ± 0.205 mg/L), and phosphate (18.59 ± 0.185 mg/L) were detected in T3 (p < 0.05). The maximum fish weight gain was recorded in T3 (26 ± 0.014%) with 1.26 ± 0.059 FCR, and the lowest fish weight gain was measured in the control group (15 ± 0.024%) with 2.19 ± 0.446 FCR (p < 0.05). Total plant length gain was reached at the maximum value in T3 (74.70 ± 1.153 cm) in comparison to other groups (p < 0.05). It was concluded that small-scale aquaponic growing bed system can be created a sustainable ecosystem which both the plant and fish can thrive and suitable for home-made production system.

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Predictive statistical modelling of cadmium content in durum wheat grain based on soil parameters

Abstract

Regulatory limits on cadmium (Cd) content in food products are tending to become stricter, especially in cereals, which are a major contributor to dietary intake of Cd by humans. This is of particular importance for durum wheat, which accumulates more Cd than bread wheat. The contamination of durum wheat grain by Cd depends not only on the genotype but also to a large extent on soil Cd availability. Assessing the phytoavailability of Cd for durum wheat is thus crucial, and appropriate methods are required. For this purpose, we propose a statistical model to predict Cd accumulation in durum wheat grain based on soil geochemical properties related to Cd availability in French agricultural soils with low Cd contents and neutral to alkaline pH (soils commonly used to grow durum wheat). The best model is based on the concentration of total Cd in the soil solution, the pH of a soil CaCl₂ extract, the cation exchange capacity (CEC), and the content of manganese oxides (Tamm's extraction) in the soil. The model variables suggest a major influence of cadmium buffering power of the soil and of Cd speciation in solution. The model successfully explains 88% of Cd variability in grains with, generally, below 0.02 mg Cd kg⁻¹ prediction error in wheat grain. Monte Carlo cross-validation indicated that model accuracy will suffice for the European Community project to reduce the regulatory limit from 0.2 to 0.15 mg Cd kg⁻¹ grain, but not for the intermediate step at 0.175 mg Cd kg⁻¹. The model will help farmers assess the risk that the Cd content of their durum wheat grain will exceed regulatory limits, and help food safety authorities test different regulatory thresholds to find a trade-off between food safety and the negative impact a too strict regulation could have on farmers.

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PDS, Merck to Launch Trial Testing Combo Therapy in Treating Certain Head and Neck Cancer Patients - Immuno-Oncology News

PDS, Merck to Launch Trial Testing Combo Therapy in Treating Certain Head and Neck Cancer Patients Immuno-Oncology News PDS Biotechnology Corporation and a subsidiary of Merck are collaborating to develop a Phase 2 clinical trial for a combination cancer treatment for people with certain types of head and neck cancer. The trial will investigate the safety and efficacy ...

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Palaeo-ecological and archaeological analysis of two Dutch Celtic fields (Zeijen-Noordse Veld and Wekerom-Lunteren): solving the puzzle of local Celtic field bank formation

Abstract

Celtic fields are the best preserved and most widely distributed type of prehistoric agricultural landscape in the Netherlands, and occur throughout north-western Europe. In this contribution, data from two excavated Dutch Celtic fields are used to explain the process of bank formation and to unravel the agricultural regime of Celtic fields. To this end, traditional archaeological methodologies and geochemical analyses are combined with detailed palaeo-ecological analyses. It is shown that Celtic field banks were constructed from a mixture of non-local soil, wetland vegetation, dung and settlement debris such as charcoal and sherds. A system was in place in which sods and plants were cut in lower-lying wetland landscapes and which were transported to the settlement, where they were presumably used as byre-bedding, became enriched with dung and were mixed with settlement debris. This mixture was carted to the fields, most likely to be spread across fallow plots as a manuring agent. From this primary, functional location, a composite sediment of agricultural sediments and the added manure was incorporated into the field banks. This process of incorporation was very slow and probably started with the uprooting of arable weeds from the fields, which were tossed to the side against the wattlework fences—together with minute quantities of soil attached to their root clusters. As a consequence of this chain of events, over the course of centuries, banks of anthropogenic sediment came to enclose fields within the Celtic field landscapes.

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Neoadjuvant Chemotherapy In Triple-Negative Breast Cancer: A Multicentric Retrospective Observational Study In Real-Life Setting

Abstract

We aimed to assess the efficacy of neoadjuvant chemotherapy (NACT) in a cohort of 213 triple-negative breast cancer (TNBC) patients treated in real-world practice at 8 Italian cancer centres. We computed descriptive statistics for all the variable of interest. Factors testing significant in univariate analysis were included in multivariate models. Survival data were compared by Kaplan-Meier curves and log-rank test.

The median follow-up was 45 months. We observed 60 (28.2%) pathological complete response (pCR). The sequential anthracyclines-taxanes-based regimens produced the highest rate of pCR (42.6%), followed by concomitant anthracycline-taxane (24.2%), and other regimens (15.6%) (p = 0.008). When analyzing the role of baseline Ki-67, a 50% cut-off was the optimal threshold value for pCR prediction (p = 0.0005). The 5-year disease-free survival (DFS) was 57.3% and the 5-year overall survival (OS) was 70.8%. In patients not achieving pCR, the optimal Ki-67 variation between biopsy and surgical specimen with prognostic relevance on long-term outcomes was 13% (p = 0.04). Patients with a Ki-67 reduction (rKi-67) < 13% had worse outcomes compared to those who experienced pCR or a rKi-67≥13%. The number of NACT cycles also affected long-term outcomes (5-year DFS 65.7% vs 51.6% in patients having received >6 cycles compared with their counterparts, p = 0.02). In multivariate analysis, node status, grading and bio-pathological treatment response (including pCR and rKi-67) impacted DFS and OS. Our results confirmed the advantage conferred by more than 6 cycles of a sequential antracycline-taxane-based NACT. Higher baseline Ki-67 values shows greater predictive significance on pathogical response, while the rKi-67 plays a prognostic role on long-term outcomes. This article is protected by copyright. All rights reserved

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Real-time monitoring of antibody microdistribution during photoimmunotherapy

Publication date: 28 August 2017
Source:Journal of Controlled Release, Volume 260
Author(s): Kinam Park




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Ultrasound targeted CNS gene delivery for Parkinson's disease treatment

Publication date: 10 September 2017
Source:Journal of Controlled Release, Volume 261
Author(s): Ching-Hsiang Fan, Chung-Yin Lin, Hao-Li Liu, Chih-Kuang Yeh
Parkinson's disease (PD) is a potent neurodegenerative disease in which a progressive loss of dopaminergic neurons eventually produces a loss of movement control and other symptoms. To date, in addition to pharmacological, non-pharmacological, and neurosurgical therapies, gene delivery has emerged as a potential therapeutic modality for PD. Effective targeted gene delivery is complicated in that gene vectors cannot penetrate the blood-brain barrier (BBB), thus clinical tests must rely on invasive intracerebral gene vector injection. Burst low-pressure focused ultrasound exposure with microbubbles has been demonstrated to noninvasively target and temporally open the BBB, opening new opportunities to transport large molecule substances into the brain for central nervous system (CNS) disease treatment, and raising the potential for noninvasive gene delivery for PD treatment. This paper reviews the underlying mechanism and current progress for focused ultrasound induced CNS gene delivery, and summarizes potential directions for further ultrasound-medicated PD gene therapy.

Graphical abstract

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