The circular RNA of peripheral blood mononuclear cells: Hsa_circ_0005836 as a new diagnostic biomarker and therapeutic target of active pulmonary tuberculosis

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Ze-Gang Zhuang, Jun-Ai Zhang, Hou-Long Luo, Gan-Bin Liu, Yuan-Bin Lu, Nan-Hai Ge, Bi-Ying Zheng, Rui Xi Li, Chen Chen, Xin Wang, Yu-Qing Liu, Feng-Hui Liu, Yong Zhou, Xiao-Zhen Cai, Zheng W. Chen, Jun-Fa Xu
It has been reported that circular RNA (circRNA) is associated with human cancer. However, few studies have been reported in active pulmonary tuberculosis (APTB). The global circRNA expression was detected in the peripheral blood mononuclear cells (PBMCs) of APTB patients (n=5) and health controls (HC) (n=5) by using high-throughput sequencing. According to the systematical bioinformatics analysis, the basic content of circRNAs and their fold changes in the two groups were calculated. We selected 6 significant differentially expressed circRNAs, hsa_circ_0005836, hsa_circ_0009128, hsa_circ_0003519, hsa_circ_0023956, hsa_circ_0078768, and hsa_circ_0088452 and validated the expression in PBMCs from APTB (n=10) and HC (n=10) by real-time quantitative reverse transcription-polymerase chain reactions (qRT-PCRs). Further, the verification of these specific circRNAs (hsa_circ_0005836 and hsa_circ_0009128) between APTB (n=34) and HC (n=30) in PBMCs was also conducted by qRT-PCRs. The RNA-seq data showed the significant differential expression of the 523 circRNAs between the APTB and HC groups (199 circRNAs were significantly up-regulated and 324 circRNAs were down-regulated). Hsa_circ_0005836 and hsa_circ_0009128 expression was significantly down-regulated in the PBMCs of APTB (P<0.05) in the samples of APTB compared to HC in our study. The gene ontology based enrichment analysis of the circRNA-miRNA-mRNAs network showed that cellular catabolic process (P=7.10E-08), regulation of metabolic process (P=2.10E-06), catalytic activity (P=3.67E-08), protein binding (P=1.71E-07), cell part (P=3.46E-06), intracellular part (P=1.71E-07), and intracellular (P=3.67E-08) were recognized in the comparisons between APTB and HC. Based on KEGG analysis, HTLV-I infection, regulation of actin cytoskeleton, neurotrophin signaling pathway and mTOR signaling pathway were relevant during tuberculosis bacillus infection. We found for the first time that hsa_circ_0005836 and hsa_circ_0009128 were significantly down-regulated in the PBMCs of APTB compared with HC. Our findings indicate hsa_circ_0005836 might serve as a novel potential biomarker for TB infection.



http://ift.tt/2vJhOTQ

Elevated intrathymic sphingosine-1-phosphate promotes thymus involution during sepsis

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Laura Kuchler, Lisa K. Sha, Annika K. Giegerich, Tilo Knape, Carlo Angioni, Nerea Ferreirós, Martina V. Schmidt, Andreas Weigert, Bernhard Brüne, Andreas von Knethen
Sepsis mouse models revealed thymus atrophy, characterised by decreased thymus weight and loss of thymocytes due to apoptosis. Mice suffered from lymphopenia, a lack of T cells in the periphery, which attenuates their ability to fight against recurring and secondary infections during sepsis progression. Key players in thymus atrophy are IL-6, which is directly involved in thymus involution, and the sphingosine-1-phosphate − sphingosine-1-phosphate receptor 1 signaling, influencing thymocytes emigration. In healthy individuals a sphingosine-1-phosphate (S1P) gradient from lymphoid organs to the circulatory system serves as signal for mature T cell egress. In the present study we investigated, whether inhibition of S1P generation improves thymus involution. In sepsis, induced by cecal ligation and puncture (CLP), S1P in the thymus increased, while it decreased in serum, thus disrupting the naturally occurring S1P gradient. As a potential source of S1P we identified increased numbers of apoptotic cells in the thymic cortex of septic mice. Pharmacological inhibition of the S1P generating sphingosine kinases, by 4- [[4-(4-Chlorophenyl)-2-thiazolyl]amino]phenol (SK I–II), administered directly following CLP, prevented thymus atrophy. This was reflected by lymphocytosis, diminished apoptosis, decreased IL-6 expression, and an unaltered thymus weight. In addition SK I-II-treatment preserved the S1P balance and prevented S1P-dependent internalization of the sphingosine-1-phosphate receptor 1. Our data suggest that inhibition of sphingosine kinase and thus, S1P generation during sepsis restores thymic T cell egress, which might improve septic outcome.



http://ift.tt/2vrXlrn

Interaction of extremophilic archaeal viruses with human and mouse complement system and viral biodistribution in mice

Publication date: October 2017
Source:Molecular Immunology, Volume 90
Author(s): Linping Wu, Kristine Buch Uldahl, Fangfang Chen, Halli Benasutti, Deborah Logvinski, Vivian Vu, Nirmal K. Banda, Xu Peng, Dmitri Simberg, Seyed Moein Moghimi
Archaeal viruses offer exceptional biophysical properties for modification and exploration of their potential in bionanotechnology, bioengineering and nanotherapeutic developments. However, the interaction of archaeal viruses with elements of the innate immune system has not been explored, which is a necessary prerequisite if their potential for biomedical applications to be realized. Here we show complement activation through lectin (via direct binding of MBL/MASPs) and alternative pathways by two extremophilic archaeal viruses (Sulfolobus monocaudavirus 1 and Sulfolobus spindle-shaped virus 2) in human serum. We further show some differences in initiation of complement activation pathways between these viruses. Since, Sulfolobus monocaudavirus 1 was capable of directly triggering the alternative pathway, we also demonstrate that the complement regulator factor H has no affinity for the viral surface, but factor H deposition is purely C3-dependent. This suggests that unlike some virulent pathogens Sulfolobus monocaudavirus 1 does not acquire factor H for protection. Complement activation with Sulfolobus monocaudavirus 1 also proceeds in murine sera through MBL-A/C as well as factor D-dependent manner, but C3 deficiency has no overall effect on viral clearance by organs of the reticuloendothelial system on intravenous injection. However, splenic deposition was significantly higher in C3 knockout animals compared with the corresponding wild type mice. We discuss the potential application of these viruses in biomedicine in relation to their complement activating properties.



http://ift.tt/2vJ6EhT

Prostaglandin E1 and Its Analog Misoprostol Inhibit Human CML Stem Cell Self-Renewal via EP4 Receptor Activation and Repression of AP-1

Publication date: Available online 30 August 2017
Source:Cell Stem Cell
Author(s): Fengyin Li, Bing He, Xiaoke Ma, Shuyang Yu, Rupali R. Bhave, Steven R. Lentz, Kai Tan, Monica L. Guzman, Chen Zhao, Hai-Hui Xue
Effective treatment of chronic myelogenous leukemia (CML) largely depends on the eradication of CML leukemic stem cells (LSCs). We recently showed that CML LSCs depend on Tcf1 and Lef1 factors for self-renewal. Using a connectivity map, we identified prostaglandin E1 (PGE1) as a small molecule that partly elicited the gene expression changes in LSCs caused by Tcf1/Lef1 deficiency. Although it has little impact on normal hematopoiesis, we found that PGE1 treatment impaired the persistence and activity of LSCs in a pre-clinical murine CML model and a xenograft model of transplanted CML patient CD34⁺ stem/progenitor cells. Mechanistically, PGE1 acted on the EP4 receptor and repressed Fosb and Fos AP-1 factors in a β-catenin-independent manner. Misoprostol, an FDA-approved EP4 agonist, conferred similar protection against CML. These findings suggest that activation of this PGE1-EP4 pathway specifically targets CML LSCs and that the combination of PGE1/misoprostol with conventional tyrosine-kinase inhibitors could provide effective therapy for CML.

Graphical abstract

Teaser

Xue and colleagues show that prostaglandin E1 (PGE1) inhibits the activity and self-renewal of human CML leukemic stem cells. Combination of PGE1 or an agonist for its receptor EP4 with conventional tyrosine kinase inhibitor treatment can effectively target CML leukemic stem cells and reduce leukemia growth.


http://ift.tt/2iIvpcT

Valosin-Containing Protein/p97 as a Novel Therapeutic Target in Acute Lymphoblastic Leukemia

Publication date: October 2017
Source:Neoplasia, Volume 19, Issue 10
Author(s): Gabriele Gugliotta, Makoto Sudo, Qi Cao, De-Chen Lin, Haibo Sun, Sumiko Takao, Ronan Le Moigne, Mark Rolfe, Sigal Gery, Markus Müschen, Michele Cavo, H. Phillip Koeffler
B acute lymphoblastic leukemia (B-ALL) cells are distinctively vulnerable to endoplasmic reticulum (ER) stress. Recently, inhibition of p97 was shown to induce ER stress and subsequently cell death in solid tumors and in multiple myeloma. We investigated the role of a novel, orally available, p97 inhibitor (CB-5083; Cleave Biosciences) in B-ALL. CB-5083 induced a significant reduction in viability in 10 human B-ALL cell lines, harboring the most common fusion-genes involved in pediatric and adult B-ALL, with IC50s ranging from 0.34 to 0.76 μM. Moreover, CB-5083 significantly reduced the colony formation of OP1 and NALM6 cells. Early and strong induction of apoptosis was demonstrated in BALL1 and OP1 cells, together with a robust cleavage of PARP. CB-5083 induced ER stress, as documented through: 1) prominent expression of chaperones (GRP78, GRP94, PDI, DNAJC3, and DNAJB9); 2) increased activation of IRE1-alpha, as demonstrated by the splicing of XBP1; and 3) activation of PERK, which resulted in a significant overexpression of CHOP, and its downstream genes. CB-5083 reduced the viability also in GRP78^−/−, GRP94^−/−, and XBP1^−/− cells, suggesting that none of these proteins alone was strictly required for CB-5083 activity. Moreover, we showed that the absence of XBP1 (XBP1^−/−) increased the sensitivity to CB-5083, leading to the hypothesis that XBP1 splicing counteracts the activity of CB-5083, probably mitigating ER stress. Finally, vincristine was synergistic with CB-5083 in both BALL1 and OP1 cells. In summary, the targeting of p97 with CB-5083 is a novel promising therapeutic approach that should be further evaluated in B-ALL.



http://ift.tt/2xMyH1u

The Stromal Microenvironment Modulates Mitochondrial Oxidative Phosphorylation in Chronic Lymphocytic Leukemia Cells

Publication date: October 2017
Source:Neoplasia, Volume 19, Issue 10
Author(s): Hima V. Vangapandu, Mary L. Ayres, Christopher A. Bristow, William G. Wierda, Michael J. Keating, Kumudha Balakrishnan, Christine M. Stellrecht, Varsha Gandhi
Peripheral blood chronic lymphocytic leukemia (CLL) cells are replicationally quiescent mature B-cells. In short-term cultures, supporting stromal cells provide a survival advantage to CLL cells by inducing transcription and translation without promoting proliferation. We hypothesized that the stromal microenvironment augments malignant B cells' metabolism to enable the cells to cope with their energy demands for transcription and translation. We used extracellular flux analysis to assess the two major energy-generating pathways, mitochondrial oxidative phosphorylation (OxPhos) and glycolysis, in primary CLL cells in the presence of three different stromal cell lines. OxPhos, measured as the basal oxygen consumption rate (OCR) and maximum respiration capacity, was significantly higher in 28 patients' CLL cells cocultured with bone marrow–derived NK.Tert stromal cells than in CLL cells cultured alone (P = .004 and <.0001, respectively). Similar OCR induction was observed in CLL cells cocultured with M2-10B4 and HS-5 stromal lines. In contrast, heterogeneous changes in the extracellular acidification rate (a measure of glycolysis) were observed in CLL cells cocultured with stromal cells. Ingenuity Pathway Analysis of CLL cells' metabolomics profile indicated stroma-mediated stimulation of nucleotide synthesis. Quantitation of ribonucleotide pools showed a significant two-fold increase in CLL cells cocultured with stromal cells, indicating that the stroma may induce CLL cellular bioenergy and the RNA building blocks necessary for the transcriptional requirement of a prosurvival phenotype. The stroma did not impact the proliferation index (Ki-67 staining) of CLL cells. Collectively, these data suggest that short-term interaction (≤24 hours) with stroma increases OxPhos and bioenergy in replicationally quiescent CLL cells.



http://ift.tt/2wSpyYC

The Imipridone ONC201 Induces Apoptosis and Overcomes Chemotherapy Resistance by Up-Regulation of Bim in Multiple Myeloma

Publication date: October 2017
Source:Neoplasia, Volume 19, Issue 10
Author(s): Yong-sheng Tu, Jin He, Huan Liu, Hans C. Lee, Hua Wang, Jo Ishizawa, Joshua E. Allen, Michael Andreeff, Robert Z. Orlowski, Richard E. Davis, Jing Yang
In multiple myeloma, despite recent improvements offered by new therapies, disease relapse and drug resistance still occur in the majority of patients. Therefore, there is an urgent need for new drugs that can overcome drug resistance and prolong patient survival after failure of standard therapies. The imipridone ONC201 causes downstream inactivation of ERK1/2 signaling and has tumoricidal activity against a variety of tumor types, while its efficacy in preclinical models of myeloma remains unclear. In this study, we treated human myeloma cell lines and patient-derived tumor cells with ONC201. Treatment decreased cellular viability and induced apoptosis in myeloma cell lines, with IC50 values of 1 to 1.5 μM, even in those with high risk features or TP53 loss. ONC201 increased levels of the pro-apoptotic protein Bim in myeloma cells, resulting from decreased phosphorylation of degradation-promoting Bim Ser69 by ERK1/2. In addition, myeloma cell lines made resistant to several standard-of-care agents (by chronic exposure) were equally sensitive to ONC201 as their drug-naïve counterparts, and combinations of ONC201 with proteasome inhibitors had synergistic anti-myeloma activity. Overall, these findings demonstrate that ONC201 kills myeloma cells regardless of resistance to standard-of-care therapies, making it promising for clinical testing in relapsed/refractory myeloma.



http://ift.tt/2xM79sT

Scholar : Dance Education in Practice, Volume 3, Issue 3, 2017 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Dance Education in Practice, Volume 3, Issue 3, 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Column Viewpoints: Letter from the Editor Elizabeth McPherson Executive Editor Associate Professor in Dance Pages: 3-3 | DOI: 10.1080/23734833.2017.1348700 NDEO Works to Cultivate Leadership in Dance Arts Education Susan McGreevy-Nichols & Shannon Dooling-Cain Pages: 4-6 | DOI: 10.1080/23734833.2017.1348701 Articles Tap to Togetherness: Engaging and Enhancing Family Relationships Through Community-Based Tap Dance Julie L. Pentz & Janice Schroeder Pages: 7-12 | DOI: 10.1080/23734833.2017.1348703 Empowered Decision Making and Dancing in Real Time: A College Residency with JoAnna Mendl Shaw JoAnna Mendl Shaw Artistic Director, Robin Collen & Chelsea Rose Pages: 13-19 | DOI: 10.1080/23734833.2017.1348715 Enhancing Musicality in Ballet Technique Classes Lauren Grant Pages: 20-26 | DOI: 10.1080/23734833.2017.1348716 Column Dance Trends: Preparing Your Studio for the School Year Miriam Giguere Pages: 27-28 | DOI: 10.1080/23734833.2017.1348727 Practical Resources for Dance Educators! NDEO's Priorities for Dance Education and the Dance Education Literature and Research Descriptive Index (DELRdi) Susan Gingrasso Pages: 29-32 | DOI: 10.1080/23734833.2017.1348722 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for South African Theatre Journal are available online

@media screen and (max-width:400px) { .two .column, .two .left, .two .right{ max-width: 100% !important; } } @media screen and (min-width: 401px) and (max-width:620px){ .two .column, .two .left, .two .right { max-width: 100% !important; } }

The online platform for Taylor & Francis Online content New for South African Theatre Journal and online now on Taylor & Francis Online: Original Articles Ritual, cultural politics and the suicides in Soyinka's Death and the King's Horseman Tertsea Ikyoive & Ayub Sheik Pages: 1-20 | DOI: 10.1080/10137548.2017.1359108 Routledge Performance Archive - http://ift.tt/1txaJgs "Take a Tour" to find out more and recommend the Archive to your librarian to arrange a free trial for your institution. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

A national survey of natural radionuclides in soils and terrestrial radiation exposure in Iran

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): M.R. Kardan, N. Fathabdi, A. Attarilar, M.T. Esmaeili-Gheshlaghi, M. Karimi, A. Najafi, S.S. Hosseini
In the past, some efforts have been made for measuring natural radioactivity and evaluating public exposure to natural radiation in certain areas of Iran especially in well-known High Level Natural Radiation Areas (HLNRA) in Ramsar and Mahallat. However, the information on radionuclide concentrations, and, consequently, terrestrial radiation exposure for many other areas are not available. There was therefore a need for a systematic and nation-wide survey. For this purpose, 979 soil samples from 31 provinces were collected. The activity concentrations of ⁴⁰K, ²²⁶Ra and ²³²Th were measured by HPGe detector. The average activity concentrations for Iran were found to be 457.7 Bq/kg for ⁴⁰K, 24.3 Bq/kg for ²²⁶Ra and 25.8 Bq/kg for ²³²Th. Results were compared with previous regional or provincial surveys. The population-weighted average outdoor and indoor annual effective dose due to external exposure to terrestrial sources of radiation are 0.06 mSv and 0.33 mSv, respectively. It was shown that there is a significant correlation between the activity concentrations of ²³²Th and ⁴⁰K in soil. In addition, the results of chi square tests show normal and lognormal distributions cannot be considered for the frequency distributions of activity concentration of ²³²Th and ²²⁶ Ra while ⁴⁰K has a normal distribution.



http://ift.tt/2vEEPrY

Environmental gamma radiation analysis for Ulsan city with the highest nuclear power plant density in Korea

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): UkJae Lee, Jun Woo Bae, Hee Reyoung Kim
This study presents a real-time measurement-based rapid radiation distribution visualization system for radionuclide recognition, which can quickly scan a contaminated environment. The system combines a portable detector with a digital map and a program for quick data treatment. Radiation information at the measurement location is transferred between a detector and a laptop. It includes environmental and artificial components, specific radionuclides, and total radionuclides. After scanning the area, the radiation distributions are comprehensively displayed in 2D and 3D maps corresponding to the measured area, all in a few tens of seconds. The proposed method was verified using the standard ¹³⁷Cs and ⁶⁰Co sources. The gamma radiation distribution of the areas measured in Ulsan city, which included non-destructive testing and radioisotope treatment facilities, hospitals, transportation spots, and residential and commercial areas, showed that Ulsan city has maintained safe levels of radiation. The system performed well. In addition, it was found that this system could detect unexpected hot spots quickly in affected environments.



http://ift.tt/2x4e97v

Influence of structural and surface properties of whey-derived peptides on zinc-chelating capacity, and in vitro gastric stability and bioaccessibility of the zinc-peptide complexes

Publication date: 1 February 2018
Source:Food Chemistry, Volume 240
Author(s): M. Chinonye Udechukwu, Brianna Downey, Chibuike C. Udenigwe
Gastrointestinal stability of zinc-peptide complexes is essential for zinc delivery. As peptide surface charge can influence their metal complex stability, we evaluated the zinc-chelating capacity and stability of zinc complexes of whey protein hydrolysates (WPH), produced with Everlase (WPH-Ever; ζ-potential, −39mV) and papain (WPH-Pap; ζ-potential, −7mV), during simulated digestion. WPH-Ever had lower amount of zinc-binding amino acids but showed higher zinc-chelating capacity than WPH-Pap. This is attributable to the highly anionic surface charge of WPH-Ever for electrostatic interaction with zinc. Release of zinc during peptic digestion was lower for WPH-Ever-zinc, and over 50% of zinc remained bound in both peptide complexes after peptic-pancreatic digestion. Fourier transform infrared spectroscopy suggests the involvement of carboxylate ion, and sidechain carbon–oxygen of aspartate/glutamate and serine/threonine in zinc-peptide complexation. The findings indicate that strong zinc chelation can promote gastric stability and impede intestinal release, for peptides intended for use as dietary zinc carriers.



http://ift.tt/2xMxesa

Seasonal variations of metal (Cd, Pb, Mn, Cu, Zn) accumulation in a voluntary species, Salix subfragilis, in unpolluted wetlands

Publication date: 1 January 2018
Source:Science of The Total Environment, Volumes 610–611
Author(s): Heung-Tae Kim, Jae Geun Kim
Willow trees are generally valuable bioindicators. Flooding during the rainy season affects the life history of Salix subfragilis, a voluntary willow species that grows in submerged wetlands, as it causes senescence of old leaves and emergence of new shoots. In this study, we assessed the potential of S. subfragilis, a Northeast Asian willow species, as a bioindicator. We also investigated seasonal variations in the concentrations of Cd, Pb, Mn, Cu, and Zn in the leaves and stems of willows growing in submerged wetlands containing low concentrations of metals, over the growing season after flooding caused by heavy rain. A significant difference in the concentrations of metals in the sediments was reflected in the leaves for Cd and Pb and in the stems for Cd, Pb, Mn, and Zn. Higher bioconcentration factors in the samples collected in spring suggest that the best monitoring time for S. subfragilis is from April to May. Whereas the concentrations of Cd, Pb, and Mn appeared to increase, especially in the leaves, the concentrations of Cu and Zn in the leaves and stems decreased toward the end of the growing season, regardless of the emergence period. Higher concentrations of Cd, Pb, and Zn were generally noted for the stems than for the leaves whereas Mn and Cu were consistently present at higher concentrations in the leaves than in the stems. These results suggest that S. subfragilis can be a useful bioindicator for Pb, as well as for Cd and Zn. Particularly, samples of new stems collected in spring could provide a good index for environmental pollution.

Graphical abstract

http://ift.tt/2wRMUxI

Coupling dispersive liquid-liquid microextraction to inductively coupled plasma atomic emission spectrometry: An oxymoron?

Publication date: 1 January 2018
Source:Talanta, Volume 176
Author(s): David Martínez, Daniel Torregrosa, Guillermo Grindlay, Luis Gras, Juan Mora
Coupling dispersive liquid-liquid micro-extraction (DLLME) to inductively coupled plasma atomic emission spectrometry (ICP-AES) is usually troublesome due to the limited plasma tolerance to the organic solvents usually employed for metal extraction. This work explores different coupling strategies allowing the multi-element determination by ICP-AES of the solutions obtained after DLLME procedures. To this end, three of the most common extractant solvents in DLLME procedures (1-undecanol, 1-butyl-3-methyl-imidazolium hexafluorophosphate and chloroform) have been selected to face most of the main problems reported in DLLME-ICP-AES coupling (i.e., those arising from the high solvent viscosity and volatility). Results demonstrate that DLLME can be successfully coupled to ICP-AES after a careful optimization of the experimental conditions. Thus, elemental analysis in 1-undecanol and 1-butyl-3-methyl-imidazolium hexafluorophosphate extracts can be achieved by ICP-AES after a simple dilution step with methanol (1:0.5). Chloroform can be directly introduced into the plasma with minimum changes in the ICP-AES configuration usually employed when operating with aqueous solutions. Diluted inorganic acid solutions (1% w w⁻¹ either nitric or hydrochloric acids) have been successfully tested for the first time as a carrier for the introduction of organic extractants in ICP-AES. The coupling strategies proposed have been successfully applied to the multi-element analysis (Al, Cu, Fe, Mn, Ni and Zn) of different water samples (i.e. marine, tap and river) by DLLME-ICP-AES.

Graphical abstract

http://ift.tt/2wRMSpA

Scholar : Aphasiology, Volume 31, Issue 11, November 2017 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Aphasiology, Volume 31, Issue 11, November 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Original Articles An examination of changes in spoken productions within constraint-induced aphasia therapy Julie Griffith, Aimee Dietz, Angel Ball, Jennifer Vannest & Jerzy P. Szaflarski Pages: 1250-1265 | DOI: 10.1080/02687038.2017.1350628 Connected speech in transient aphasias after left hemisphere resective surgery Angelica McCarron, Ashley Chavez, Miranda C. Babiak, Mitchel S. Berger, Edward F. Chang & Stephen M. Wilson Pages: 1266-1281 | DOI: 10.1080/02687038.2017.1278740 A comparison of visual scene and grid displays for people with chronic aphasia: a pilot study to improve communication using AAC Kris Brock, Rajinder Koul, Melinda Corwin & Ralf Schlosser Pages: 1282-1306 | DOI: 10.1080/02687038.2016.1274874 Effects of word frequency and contextual predictability on sentence reading in aphasia: an eye movement analysis Anneline Huck , Robin L. Thompson , Madeline Cruice & Jane Marshall Pages: 1307-1332 | DOI: 10.1080/02687038.2017.1278741 Adaptation of melodic intonation therapy to Spanish: a feasibility pilot study Ana María Haro-Martínez, Victoria Eugenia García-Concejero, Amparo López-Ramos, Enedina Maté-Arribas, José López-Táppero, Genny Lubrini, Exuperio Díez-Tejedor & Blanca Fuentes Pages: 1333-1343 | DOI: 10.1080/02687038.2017.1279731 Short Report Decision-making capacity in aphasia: SLT's contribution in England | Megan McCormick, Arpita Bose & Theodoros Marinis Pages: 1344-1358 | DOI: 10.1080/02687038.2017.1355441 Routledge Psychology 2017 sponsor of BPS #PsychCrunch podcasts. Access 25 journal articles: http://bit.ly/psychcrunch2017 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for Journal for Cultural Research are available online

The online platform for Taylor & Francis Online content New for Journal for Cultural Research and online now on Taylor & Francis Online: Original Articles Critical proximity Stefan Herbrechter Pages: 1-14 | DOI: 10.1080/14797585.2017.1370485 'The letting go': the horror of being orphaned in Nicolas Winding Refn's cinema Mark Featherstone Pages: 1-18 | DOI: 10.1080/14797585.2017.1369686 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Anxiety, Stress, & Coping, Volume 30, Issue 6, November 2017 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Anxiety, Stress, & Coping, Volume 30, Issue 6, November 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Articles High dose alcohol consumption predicts less reduction in post-traumatic stress symptoms after a campus mass shooting Jacob B. Holzman, David P. Valentiner , Susan M. Hannan, Douglas G. Wallace & Holly K. Orcutt Pages: 609-618 | DOI: 10.1080/10615806.2017.1348297 The effects of arousal reappraisal on stress responses, performance and attention Nadine Sammy, Paul A. Anstiss, Lee J. Moore, Paul Freeman, Mark R. Wilson & Samuel J. Vine Pages: 619-629 | DOI: 10.1080/10615806.2017.1330952 The costly burden of an inauthentic self: insecure self-esteem predisposes to emotional exhaustion by increasing reactivity to negative events Guido Alessandri, Enrico Perinelli, Evelina De Longis, Valentina Rosa, Annalisa Theodorou & Laura Borgogni Pages: 630-646 | DOI: 10.1080/10615806.2016.1262357 Specificity of peer difficulties to social anxiety in early adolescence: categorical and dimensional analyses with clinical and community samples Martha C. Early, Bridget K. Biggs, Kalani P. Makanui, John Paul Legerski, Jason Van Allen, Allison R. Elledge & Stephen P. Whiteside Pages: 647-660 | DOI: 10.1080/10615806.2017.1348296 Hair cortisol in relation to acute and post-traumatic stress symptoms in children and adolescents Joana Straub, Lena Marie Klaubert, Susann Schmiedgen, Clemens Kirschbaum & Lutz Goldbeck Pages: 661-670 | DOI: 10.1080/10615806.2017.1355458 The natural course of anxiety symptoms in early adolescence: factors related to persistence Núria Voltas , Carmen Hernández-Martínez , Victoria Arija & Josefa Canals Pages: 671-686 | DOI: 10.1080/10615806.2017.1347642 Development of a coping with stress scale for a non-western population of children and adolescents Ilgın Gökler DanIşman, Nejla Yıldız & İbrahim Yiğit Pages: 687-701 | DOI: 10.1080/10615806.2017.1330951 Role of event centrality and emotion regulation in posttraumatic stress disorder symptoms among internally displaced persons JohnBosco Chika Chukwuorji , Chuka Mike Ifeagwazi & John E. Eze Pages: 702-715 | DOI: 10.1080/10615806.2017.1361936 Brief Report Social anxiety and emotion regulation flexibility: considering emotion intensity and type as contextual factors Mia S. O'Toole, Robert Zachariae & Douglas S. Mennin Pages: 716-724 | DOI: 10.1080/10615806.2017.1346792 QHW publishes new thematic cluster on ADHD International Journal of Qualitative Studies on Health and Well-being (QHW) is an open access peer reviewed scientific journal that provides a forum for the exchange of data, knowledge, theoretical framework and methods on health and well-being.Read the journal's thematic cluster on ADHD today. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

The views of children and young people on the use of silk garments for the treatment of eczema: a nested qualitative study within the CLOTHES randomised controlled trial

Summary

Background

Many children suffer with skin diseases, but to date, most dermatological research has been done 'on' rather than 'with' children; in this study we actively sought the experiences of children and young people. Atopic eczema (AE) is a chronic, itchy, inflammatory skin condition that affects around 20% of children and can impact on health and wellbeing for children and their families. The role of specialist clothing in the management of AE is poorly understood.

Objectives

The aim of this study, which was nested in a randomised controlled trial was to qualitatively examine child participants' experiences of using silk garments for the treatment of AE.

Methods

Eighteen children aged 5-15, who took part in the CLOTHES trial, participated in age-appropriate individual interviews or focus groups.

Results

Thematic analysis generated 4 themes directly related to the garments: i) expectations of the garments; ii) wearing the silk garments; iii) did they help? and iv) thoughts about the garments. The conclusions from this nested qualitative study are that: there was some limited improvement in eczema for some children but that the hoped for 'miracle cure' did not transpire. A mixed picture of knowledge, beliefs and experiences of using the silk garments emerged.

Conclusion

Engaging children in the evaluation of the garments provided first hand nuanced insights that enhanced understanding of the CLOTHES study as a whole. This nested study demonstrates that children can and indeed want to be engaged in dermatological research in meaningful ways that add to our understanding of treatment options.

This article is protected by copyright. All rights reserved.

http://ift.tt/2vISopH

Prevalence and determinants of seborrheic dermatitis in a middle aged and elderly population: the Rotterdam Study

Abstract

Background

Seborrheic dermatitis is a chronic relapsing inflammatory skin disease with unclear pathophysiological mechanisms.

Objective

To establish which lifestyle and physiological determinants are associated with seborrheic dermatitis.

Methods

Seborrheic dermatitis was diagnosed by a trained physician during a full body skin examination within the Rotterdam Study, a prospective population-based cohort study in middle aged and elderly. The current design is a comparative cross-sectional study embedded in the Rotterdam Study. Potential factors were identified from the literature and analysed in a multivariable logistic regression, including: age, sex, obesity, skin colour, stress, depression, education level, hypertension, climate, xerosis cutis, alcohol and tobacco use.

Results

Of the 5,498 participants, 788 participants were diagnosed with seborrheic dermatitis (14.3%). We found associations between seborrheic dermatitis and male sex (adjusted OR 2.09; 95% CI: 1.77-2.47), darker skin (adjusted OR 0.39; 95% CI: 0.22-0.69), season (summer vs winter: adjusted OR 0.63; 95% CI: 0.48-0.82) and generalized xerosis cutis (adjusted OR 1.41; 95% CI 1.12-1.80).

Conclusion

Seborrheic dermatitis is one of most common inflammatory dermatoses in middle and elderly aged individuals, especially during winter period. Men, and people with a light and dry skin were most likely to have seborrheic dermatitis.

This article is protected by copyright. All rights reserved.

http://ift.tt/2vqMzBS

Why Do the Children (Pretend) Play?

Publication date: Available online 29 August 2017
Source:Trends in Cognitive Sciences
Author(s): Angeline S. Lillard
Pretend play appears to be an evolved behavior because it is universal and appears on a set schedule. However, no specific functions have been determined for pretend play and empirical tests for its functions in humans are elusive. Yet animal play fighting can serve as an analog, as both activities involve as-if, metacommunicative signaling and symbolism. In the rat and some other animals, adaptive functions of play fighting include assisting social behavior and emotion regulation. Research is presented suggesting that pretend play might serve similar functions for humans.



http://ift.tt/2gofj7s

Tumour radiosensitivity is associated with immune activation in solid tumours

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): Tobin Strom, Louis B. Harrison, Anna R. Giuliano, Michael J. Schell, Steven A. Eschrich, Anders Berglund, William Fulp, Ram Thapa, Domenico Coppola, Sungjune Kim, Jessica Frakes, John Foekens, James J. Mulé, Javier F. Torres-Roca
PurposeOur goal was to determine whether tumour radiosensitivity is associated with activation of the immune system across all tumour types as measured by two gene expression signatures (GESs).MethodsWe identified 10,240 genomically profiled distinct solid primary tumours with gene expression analysis available from an institutional de-identified database. Two separate GESs were included in the analysis, the radiosensitivity index (RSI) GES (a 10-gene GES as a measure of radiosensitivity) and the 12-chemokine (12-CK) signature (a 12-gene GES as a measure of immune activation). We tested whether the RSI and 12-CK were associated with each other across all tumour samples and, in an exploratory analysis, their prognostic significance in predicting distant metastasis-free survival (DMFS) among a well-characterised, independent cohort of 282 early-stage breast cancer cases treated with surgery and post-operative radiation alone without systemic therapy. The lower the RSI score, the higher the tumour radiosensitivity; whereas, the higher the 12-CK score the higher the immune activation.ResultsUsing an RSI cut-point of ≤0.3745, RSI-low tumours (n = 4,291, 41.9%) had a significantly higher median 12-CK GES value (0.54 [−0.136, 1.095]) compared with RSI-high tumours (−0.17 [–0.82, 0.42]; p < 0.001) across all tumour samples, indicating that radiosensitivity is associated with immune activation. In an exploratory analysis of early-stage breast cancer cases, a multivariable model with patient age, RSI and 12-CK provided a strong composite model for DMFS (p = 0.02), with RSI (hazard ratio [HR] 0.63 [95% confidence interval 0.36, 1.09]) and 12-CK (HR 0.66 [0.41, 1.04]) each providing comparable contributions.ConclusionsTumour radiosensitivity is associated with immune activation as measured by the two GESs.



http://ift.tt/2vDCD40

Breast cancer in young women and prognosis: How important are proliferation markers?

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): Hanna Fredholm, Kristina Magnusson, Linda S. Lindström, Nicholas P. Tobin, Henrik Lindman, Jonas Bergh, Lars Holmberg, Fredrik Pontén, Jan Frisell, Irma Fredriksson
AimCompared to middle-aged women, young women with breast cancer have a higher risk of systemic disease. We studied expression of proliferation markers in relation to age and subtype and their association with long-term prognosis.MethodsDistant disease-free survival (DDFS) was studied in 504 women aged <40 years and 383 women aged ≥40 years from a population-based cohort. Information on patient characteristics, treatment and follow-up was collected from medical records. Tissue microarrays were produced for analysis of oestrogen receptor, progesterone receptor (PR), Her2, Ki-67 and cyclins.ResultsYoung women with luminal tumours had significantly higher expression of Ki-67 and cyclins. Proliferation markers were prognostic only within this subtype. Ki-67 was a prognostic indicator only in young women with luminal PR+ tumours. The optimal cut-off for Ki-67 varied by age. High expression of cyclin E1 conferred a better DDFS in women aged <40 years with luminal PR− tumours (hazard ratio [HR] 0.47 [0.24–0.92]). Age <40 years was an independent risk factor of DDFS exclusively in women with luminal B PR+ tumours (HR 2.35 [1.22–4.50]). Young women with luminal B PR− tumours expressing low cyclin E1 had a six-fold risk of distant disease compared with luminal A (HR 6.21 [2.17–17.6]).ConclusionsThe higher expression of proliferation markers in young women does not have a strong impact on prognosis. Ki-67 is only prognostic in the subgroup of young women with luminal PR+ tumours. The only cyclin adding prognostic value beyond subtype is cyclin E1. Age is an independent prognostic factor only in women with luminal B PR+ tumours.



http://ift.tt/2x3EOBr

Current margin practice and effect on re-excision rates following the publication of the SSO-ASTRO consensus and ABS consensus guidelines: a national prospective study of 2858 women undergoing breast-conserving therapy in the UK and Ireland

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): Sarah Shuk-Kay Tang, Sarantos Kaptanis, James B. Haddow, Giuseppina Mondani, Beatrix Elsberger, Marios Konstantinos Tasoulis, Christine Obondo, Neil Johns, Wisam Ismail, Asim Syed, Panayioti Kissias, Mary Venn, Souganthy Sundaramoorthy, Gareth Irwin, Amtul S. Sami, Dalia Elfadl, Alice Baggaley, Dionysios Dennis Remoundos, Fiona Langlands, Petros Charalampoudis, Zoe Barber, Werbena L.S. Hamilton-Burke, Ayesha Khan, Chiara Sirianni, Louise Anne-Marie Grant Merker, Sunita Saha, Risha Arun Lane, Sharat Chopra, Sophie Dupré, Aiden T. Manning, Edward R. St John, Aya Musbahi, Nokwanda Dlamini, Caitlin L. McArdle, Chloe Wright, James O. Murphy, Ravi Aggarwal, Matei Dordea, Karen Bosch, Donna Egbeare, Hisham Osman, Salim Tayeh, Faraz Razi, Javeria Iqbal, Serena F.C. Ledwidge, Vanessa Albert
IntroductionThere is variation in margin policy for breast conserving therapy (BCT) in the UK and Ireland. In response to the Society of Surgical Oncology and American Society for Radiation Oncology (SSO-ASTRO) margin consensus ('no ink on tumour' for invasive and 2 mm for ductal carcinoma in situ [DCIS]) and the Association of Breast Surgery (ABS) consensus (1 mm for invasive and DCIS), we report on current margin practice and unit infrastructure in the UK and Ireland and describe how these factors impact on re-excision rates.MethodsA trainee collaborative-led multicentre prospective study was conducted in the UK and Ireland between 1st February and 31st May 2016. Data were collected on consecutive BCT patients and on local infrastructure and policies.ResultsA total of 79 sites participated in the data collection (75% screening units; average 372 cancers annually, range 70–900). For DCIS, 53.2% of units accept 1 mm and 38% accept 2-mm margins. For invasive disease 77.2% accept 1 mm and 13.9% accept 'no ink on tumour'. A total of 2858 patients underwent BCT with a mean re-excision rate of 17.2% across units (range 0–41%). The re-excision rate would be reduced to 15% if all units applied SSO-ASTRO guidelines and to 14.8% if all units followed ABS guidelines. Of those who required re-operation, 65% had disease present at margin.ConclusionThere continues to be large variation in margin policy and re-excision rates across units. Altering margin policies to follow either SSO-ASTRO or ABS guidelines would result in a modest reduction in the national re-excision rate. Most re-excisions are for involved margins rather than close margins.



http://ift.tt/2vDS4Jh

Hypermutated tumours in the era of immunotherapy: The paradigm of personalised medicine

Publication date: October 2017
Source:European Journal of Cancer, Volume 84
Author(s): Laetitia Nebot-Bral, David Brandao, Loic Verlingue, Etienne Rouleau, Olivier Caron, Emmanuelle Despras, Yolla El-Dakdouki, Stéphane Champiat, Said Aoufouchi, Alexandra Leary, Aurélien Marabelle, David Malka, Nathalie Chaput, Patricia L. Kannouche
Immune checkpoint inhibitors have demonstrated unprecedented clinical activity in a wide range of cancers. Significant therapeutic responses have recently been observed in patients presenting mismatch repair-deficient (MMRD) tumours. MMRD cancers exhibit a remarkably high rate of mutations, which can result in the formation of neoantigens, hypothesised to enhance the antitumour immune response. In addition to MMRD tumours, cancers mutated in the exonuclease domain of the catalytic subunit of the DNA polymerase epsilon (POLE) also exhibit an ultramutated genome and are thus likely to benefit from immunotherapy. In this review, we provide an overview of recent data on hypermutated tumours, including MMRD and POLE-mutated cancers, with a focus on their distinctive clinicopathological and molecular characteristics as well as their immune environment. We also discuss the emergence of immune therapy to treat these hypermutated cancers, and we comment on the recent Food and Drug Administration approval of an immune checkpoint inhibitor, the programmed cell death 1 antibody (pembrolizumab, Keytruda), for the treatment of patients with metastatic MMRD cancers regardless of the tumour type. This breakthrough represents a turning point in the management of these hypermutated tumours and paves the way for broader strategies in immunoprecision medicine.



http://ift.tt/2x3xkhS

Emerging Roles for the Lysosome in Lipid Metabolism

Publication date: Available online 30 August 2017
Source:Trends in Cell Biology
Author(s): Ashley M. Thelen, Roberto Zoncu
Precise regulation of lipid biosynthesis, transport, and storage is key to the homeostasis of cells and organisms. Cells rely on a sophisticated but poorly understood network of vesicular and nonvesicular transport mechanisms to ensure efficient delivery of lipids to target organelles. The lysosome stands at the crossroads of this network due to its ability to process and sort exogenous and endogenous lipids. The lipid-sorting function of the lysosome is intimately connected to its recently discovered role as a metabolic command-and-control center, which relays multiple nutrient cues to the master growth regulator, mechanistic target of rapamycin complex (mTORC)1 kinase. In turn, mTORC1 potently drives anabolic processes, including de novo lipid synthesis, while inhibiting lipid catabolism. Here, we describe the dual role of the lysosome in lipid transport and biogenesis, and we discuss how integration of these two processes may play important roles both in normal physiology and in disease.



http://ift.tt/2wn9RWi

Chromosome biology: Different turfs for cohesin and condensin

http://ift.tt/2x3FjeU

Model organisms: New tools, new insights — probing social behaviour in ants

http://ift.tt/2vDxNUd

Genetic engineering: Pigs without PERVs

http://ift.tt/2x3A5zJ

Beyond editing to writing large genomes

Advances in genome sequencing, editing and synthetic biology have enhanced the feasibility of large-scale genome engineering, termed genome writing. In this Opinion article, Chari and Church discuss the strengths and limitations of diverse strategies for genome writing, including extensively modifying existing genomes versus synthesizing genomes de novo, and they provide future visions for writing large genomes.

http://ift.tt/2vDx1Xi

Comparison of the laryngeal mask airway supreme and the i-gel in paralysed elderly patients: A randomised controlled trial.

BACKGROUND: The laryngeal mask airway supreme (LMA-S) and i-gel are both popular second-generation supraglottic airway devices that have been widely studied in surgical patients, but their differences in clinical performance in the elderly are not clear. OBJECTIVE: We compared the efficacy and safety of the LMA-S and i-gel in anaesthetised and paralysed elderly patients. DESIGN: A prospective, randomised and parallel study. SETTING: Single-centre trial, study period January 2014 from to October 2016. PATIENTS: One hundred and six elderly patients who underwent urological or orthopaedic surgery with an expected duration less than 2 h. INTERVENTION: Patients were allocated to either the LMA-S (n = 53) or i-gel (n = 53) group. All insertions were performed in a standardised manner according to the manufacturers' instructions. MAIN OUTCOME MEASURES: Our primary endpoint was the rate of successful insertion at the first attempt. The adequacy of positive pressure ventilation and airway sealing, fibreoptic laryngoscopy grades and stability of airway maintenance during anaesthesia were also assessed. RESULTS: Although the rate of successful insertion at the first attempt was similar between the two groups (94.3 vs. 82.7%, P = 0.072), more patients required device manipulation during insertion with the LMA-S than the i-gel (42.3 vs. 18.9%, P = 0.011). Good fibreoptic laryngoscopy grades were significantly more common with the i-gel than the LMA-S (79.3 vs. 55.8%, P = 0.042), and peak inspiratory pressures were lower in the i-gel group both immediately after insertion and at the end of surgery. Leak pressures were significantly higher in the i-gel group than the LMA-S group, both immediately after insertion and at the end of surgery (25.8 vs. 23.0, P = 0.036; and 28.1 vs. 23.7, P

http://ift.tt/2x3zjm7

Topical antifungal treatment prevents recurrence of toenail onychomycosis following cure

Abstract

Recurrence rates are high for onychomycosis, with prophylactic topical antifungal use proposed to counter recurrence. Although this is a reasonable action for many clinicians, few studies have been conducted on the efficacy of topical prophylaxis. A retrospective chart review (2010–2015) was conducted in patients receiving oral terbinafine or itraconazole for toenail onychomycosis. Following complete cure, a topical antifungal (amorolfine, bifonazole, ciclopirox olamine, or terbinafine spray) was used weekly as prophylaxis. Recurrence was recorded along with patient characteristics including demographics and concomitant medical conditions. Data from 320 patients were collected. Recurrence was significantly lower in patients receiving topical antifungal prophylaxis than in no prophylactic treatment following oral terbinafine (p < .001), but not itraconazole (p = .185). Regardless of oral treatment, the use of topical antifungals as prophylaxis (p < .001) decreased, and the number of affected toenails (p = .048) and family history of fungal infections (p < .001) increased the likelihood that recurrence would occur. This study supports the use of topical antifungal medications as prophylactic treatment to help prevent recurrence of toenail onychomycosis and suggests that those with a family history of fungal infections should be closely monitored.

http://ift.tt/2wnykeo

Lupus panniculitis refractory to multiple therapies treated successfully with rituximab: A case report and literature review

http://ift.tt/2whdj6y

Erratum to: The Future of Periodontal-Systemic Associations: Raising the Standards

http://ift.tt/2wRhLdC

The Organization of Working Memory Networks is Shaped by Early Sensory Experience

Abstract

Early deafness results in crossmodal reorganization of the superior temporal cortex (STC). Here, we investigated the effect of deafness on cognitive processing. Specifically, we studied the reorganization, due to deafness and sign language (SL) knowledge, of linguistic and nonlinguistic visual working memory (WM). We conducted an fMRI experiment in groups that differed in their hearing status and SL knowledge: deaf native signers, and hearing native signers, hearing nonsigners. Participants performed a 2-back WM task and a control task. Stimuli were signs from British Sign Language (BSL) or moving nonsense objects in the form of point-light displays. We found characteristic WM activations in fronto-parietal regions in all groups. However, deaf participants also recruited bilateral posterior STC during the WM task, independently of the linguistic content of the stimuli, and showed less activation in fronto-parietal regions. Resting-state connectivity analysis showed increased connectivity between frontal regions and STC in deaf compared to hearing individuals. WM for signs did not elicit differential activations, suggesting that SL WM does not rely on modality-specific linguistic processing. These findings suggest that WM networks are reorganized due to early deafness, and that the organization of cognitive networks is shaped by the nature of the sensory inputs available during development.

http://ift.tt/2wRKDmi

Denser Growing Fiber Connections Induce 3-hinge Gyral Folding

Abstract

Recent studies have shown that quantitative description of gyral shape patterns offers a novel window to examine the relationship between brain structure and function. Along this research line, this paper examines a unique and interesting type of cortical gyral region where 3 different gyral crests meet, termed 3-hinge gyral region. We extracted 3-hinge gyral regions in macaque/chimpanzee/human brains, quantified and compared the relevant DTI-derived fiber densities in 3-hinge and 2-hinge gyral regions. Our observations consistently showed that DTI-derived fiber densities in 3-hinge regions are much higher than those in 2-hinge regions. Therefore, we hypothesize that besides the cortical expansion, denser fiber connections can induce the formation of 3-hinge gyri. To examine the biomechanical basis of this hypothesis, we constructed a series of 3-dimensional finite element soft tissue models based on continuum growth theory to investigate fundamental biomechanical mechanisms of consistent 3-hinge gyri formation. Our computational simulation results consistently showed that during gyrification gyral regions with higher concentrations of growing axonal fibers tend to form 3-hinge gyri. Our integrative approach combining neuroimaging data analysis and computational modeling appears effective in probing a plausible theory of 3-hinge gyri formation and providing new insights into structural and functional cortical architectures and their relationship.

http://ift.tt/2xLUCWu

Structural Connections of Functionally Defined Human Insular Subdivisions

Abstract

The organization of the human insular cortex has traditionally been considered as an anterior–posterior dichotomy, where anterior and posterior subdivisions have unique structural and functional connections. However, recent functional neuroimaging research proposes a tripartite organization where insular subdivisions have both unique and overlapping functional profiles. Studies examining unique profiles show that the dorsal anterior insula (dAI) has connections with frontal areas supporting higher-level cognitive processes, the ventral anterior insula (vAI) has connections with limbic areas supporting affective processes, and the posterior insula (PI) has connections with sensorimotor areas supporting interoceptive processes. Studies examining overlapping profiles demonstrate that all 3 subdivisions can also have similar functional profiles. The structural organization supporting a functional tripartite insula organization presenting with overlapping and unique connections is currently unknown. We used a large HARDI diffusion magnetic resonance imaging (MRI) dataset (n = 199) to demonstrate novel visualizations of insula white matter tracts supporting a tripartite structure–function insula organization. Overlapping connections of all 3 insula subdivisions consisted of association pathways (inferior fronto-occipital fasciculus, uncinate fasciculus, arcuate fasciculus) while unique connections included the corona radiata, subcortical-cortical tracts, and horizontal and u-shaped tracts. These results generally support a tripartite structure–function organization of the insular cortex, with subdivisions that exhibit both overlapping and unique connectivity profiles.

http://ift.tt/2gowOVr

Cerebral Vein Malformations Result from Loss of Twist1 Expression and BMP Signaling from Skull Progenitor Cells and Dura

Publication date: Available online 30 August 2017
Source:Developmental Cell
Author(s): Max A. Tischfield, Caroline D. Robson, Nicole M. Gilette, Shek Man Chim, Folasade A. Sofela, Michelle M. DeLisle, Alon Gelber, Brenda J. Barry, Sarah MacKinnon, Linda R. Dagi, Jeremy Nathans, Elizabeth C. Engle
Dural cerebral veins (CV) are required for cerebrospinal fluid reabsorption and brain homeostasis, but mechanisms that regulate their growth and remodeling are unknown. We report molecular and cellular processes that regulate dural CV development in mammals and describe venous malformations in humans with craniosynostosis and TWIST1 mutations that are recapitulated in mouse models. Surprisingly, Twist1 is dispensable in endothelial cells but required for specification of osteoprogenitor cells that differentiate into preosteoblasts that produce bone morphogenetic proteins (BMPs). Inactivation of Bmp2 and Bmp4 in preosteoblasts and periosteal dura causes skull and CV malformations, similar to humans harboring TWIST1 mutations. Notably, arterial development appears normal, suggesting that morphogens from the skull and dura establish optimal venous networks independent from arterial influences. Collectively, our work establishes a paradigm whereby CV malformations result from primary or secondary loss of paracrine BMP signaling from preosteoblasts and dura, highlighting unique cellular interactions that influence tissue-specific angiogenesis in mammals.

Graphical abstract

Teaser

By characterizing dural cerebral vein malformations in TWIST1 mutation-positive humans and mouse models with craniosynostosis, Tischfield et al. report that cerebral vein angiogenesis requires paracrine BMP signaling from skull preosteoblasts and periosteal dura. The effects are independent from arterial influences and highlight unique cellular interactions that pattern tissue-specific vascular networks.


http://ift.tt/2goVzR9

Chromosome biology: Different turfs for cohesin and condensin

Nature Reviews Genetics. doi:10.1038/nrg.2017.71

Author: Eytan Zlotorynski

http://ift.tt/2x2OFYc

Model organisms: New tools, new insights — probing social behaviour in ants

Nature Reviews Genetics. doi:10.1038/nrg.2017.70

Author: Dorothy Clyde

http://ift.tt/2x3cHT4

Genetic engineering: Pigs without PERVs

Nature Reviews Genetics. doi:10.1038/nrg.2017.73

Author: Linda Koch

http://ift.tt/2vDbZrP

Beyond editing to writing large genomes

Nature Reviews Genetics. doi:10.1038/nrg.2017.59

Authors: Raj Chari & George M. Church

http://ift.tt/2vDvq3S

Treatment of cutaneous iatrogenic Kaposi sarcoma with topical timolol

http://ift.tt/2vIkfGe

Issue Information - JEB

http://ift.tt/2vqirGx

Neutrophilic dermatosis of hands preceding extensive small cell lung cancer

http://ift.tt/2vIrZZ3

Issue Information - TOC

http://ift.tt/2vqM3nn

Range expansion potential of two co-occurring invasive vines to marginal habitats in Turkey

Publication date: October 2017
Source:Acta Oecologica, Volume 84
Author(s): Shahid Farooq, Sonnur Tad, Huseyin Onen, Hikmet Gunal, Ugur Caldiran, Cumali Ozaslan
Niche distribution models accurately predict the potential distribution range of invasive plants into new habitats based on their climatic requirements in the native regions. However, these models usually ignore the marginal habitats which can limit the distribution of exotic plants. We therefore tested the seedling survival, growth and nutrient acquisition capabilities of two co-occurring invasive vines [Persicaria perfoliata (L.) H. Gross and Sicyos angulatus L.] in three different manipulative greenhouse experiments to infer their range expansion potential to marginal habitats in Turkey. First experiment included five different moisture availability regimes (100, 75, 50, 25 and 12.5% available water), second experiment consisted of four different salinity levels (0, 3, 6 and 12 dSm⁻¹ soil salinity) and third experiment had four different soil textures (clay-1, clay-2, sandy loam and silt-clay-loam). Seedling mortality was only observed under extreme moisture deficiency in both plant species, while most of the transplanted seedlings of both species did not survive under 6 and 12 dSm⁻¹ salinity levels. Soil textures had no effect on seedling survival. POLPE better tolerated low moisture availability and high salinity compared to SIYAN. Biomass production in both plant species was linearly reduced with increasing salinity and moisture deficiency. SIYAN invested more resources towards shoot, accumulated higher K and P, whereas POLPE maintained higher root-to-shoot ratio under all experimental conditions. Both plant species employed different strategies to cope with adverse environmental conditions, but failed to persist under high soil salinity and moisture deficiency. Our study suggest that both plant species have limited potential of range expansion to marginal habitats and will be limited to moist and humid areas only. Therefore, further research activities should be concentrated in these regions to develop effective management strategies against both species.



http://ift.tt/2xwzOCW

Dopaminergic dysfunction in neurodevelopmental disorders: recent advances and synergistic technologies to aid basic research

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): J Elliott Robinson, Viviana Gradinaru
Neurodevelopmental disorders (NDDs) represent a diverse group of syndromes characterized by abnormal development of the central nervous system and whose symptomatology includes cognitive, emotional, sensory, and motor impairments. The identification of causative genetic defects has allowed for creation of transgenic NDD mouse models that have revealed pathophysiological mechanisms of disease phenotypes in a neural circuit- and cell type-specific manner. Mouse models of several syndromes, including Rett syndrome, Fragile X syndrome, Angelman syndrome, Neurofibromatosis type 1, etc., exhibit abnormalities in the structure and function of dopaminergic circuitry, which regulates motivation, motor behavior, sociability, attention, and executive function. Recent advances in technologies for functional circuit mapping, including tissue clearing, viral vector-based tracing methods, and optical readouts of neural activity, have refined our knowledge of dopaminergic circuits in unperturbed states, yet these tools have not been widely applied to NDD research. Here, we will review recent findings exploring dopaminergic function in NDD models and discuss the promise of new tools to probe NDD pathophysiology in these circuits.

Graphical abstract

http://ift.tt/2x3dB1x

Chromatin-remodeling enzymes in control of Schwann cell development, maintenance and plasticity

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Claire Jacob
Gene regulation is essential for cellular differentiation and plasticity. Schwann cells (SCs), the myelinating glia of the peripheral nervous system (PNS), develop from neural crest cells to mature myelinating SCs and can at early developmental stage differentiate into various cell types. After a PNS lesion, SCs can also convert into repair cells that guide and stimulate axonal regrowth, and remyelinate regenerated axons. What controls their development and versatile nature? Several recent studies highlight the key roles of chromatin modifiers in these processes, allowing SCs to regulate their gene expression profile and thereby acquire or change their identity and quickly react to their environment.



http://ift.tt/2x3da7E

Mechanisms of Müller glial cell morphogenesis

Publication date: December 2017
Source:Current Opinion in Neurobiology, Volume 47
Author(s): Ryan B MacDonald, Mark Charlton-Perkins, William A Harris
Müller Glia (MG), the radial glia cells of the retina, have spectacular morphologies subserving their enormous functional complexity. As early as 1892, the great neuroanatomist Santiago Ramon y Cajal studied the morphological development of MG, defining several steps in their morphogenesis [1,2]. However, the molecular cues controlling these developmental steps remain poorly understood. As MG have roles to play in every cellular and plexiform layer, this review discusses our current understanding on how MG morphology may be linked to their function, including the developmental mechanisms involved in MG patterning and morphogenesis. Uncovering the mechanisms governing glial morphogenesis, using transcriptomics and imaging, may provide shed new light on the pathophysiology and treatment of human neurological disorders.

Graphical abstract

http://ift.tt/2vDqyvK

Quantifying behavior to solve sensorimotor transformations: advances from worms and flies

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Adam J Calhoun, Mala Murthy
The development of new computational tools has recently opened up the study of natural behaviors at a precision that was previously unachievable. These tools permit a highly quantitative analysis of behavioral dynamics at timescales that are well matched to the timescales of neural activity. Here we examine how combining these methods with established techniques for estimating an animal's sensory experience presents exciting new opportunities for dissecting the sensorimotor transformations performed by the nervous system. We focus this review primarily on examples from Caenorhabditis elegans and Drosophila melanogaster—for these model systems, computational approaches to characterize behavior, in combination with unparalleled genetic tools for neural activation, silencing, and recording, have already proven instrumental for illuminating underlying neural mechanisms.



http://ift.tt/2vDnhw9

From the statistics of connectivity to the statistics of spike times in neuronal networks

Publication date: October 2017
Source:Current Opinion in Neurobiology, Volume 46
Author(s): Gabriel Koch Ocker, Yu Hu, Michael A Buice, Brent Doiron, Krešimir Josić, Robert Rosenbaum, Eric Shea-Brown
An essential step toward understanding neural circuits is linking their structure and their dynamics. In general, this relationship can be almost arbitrarily complex. Recent theoretical work has, however, begun to identify some broad principles underlying collective spiking activity in neural circuits. The first is that local features of network connectivity can be surprisingly effective in predicting global statistics of activity across a network. The second is that, for the important case of large networks with excitatory-inhibitory balance, correlated spiking persists or vanishes depending on the spatial scales of recurrent and feedforward connectivity. We close by showing how these ideas, together with plasticity rules, can help to close the loop between network structure and activity statistics.



http://ift.tt/2x2GECq

Digit ratio 2D:4D is a possible indicator for androgenetic alopecia in males

Summary

Background

Androgenetic alopecia (AGA) is the most common hair loss. The 2D:4D digit ratio refers to the ratio of the length of the second finger to that of the fourth finger and is thought as a marker of prenatal androgen exposure.

Objectives

There are many studies which have examined the relationship between 2D:4D ratio and some other diseases. In this study, we evaluated the relationship between digit ratio 2D:4D and AGA.

Methods

The study group was composed of a male with AGA and healthy controls. The lengths of patients' second and fourth fingers were measured using a digital caliper with a resolution of 0.01 mm. Finger length was measured on the palmar side of the hand from the basal metacarpophalangeal crease. The 2D:4D ratio was obtained by dividing the length of the second finger by the length of the fourth finger.

Results

A total of 99 males who have androgenetic alopecia with a score of grade III or more and 90 controls were included. The mean age of AGA group was 29.72 ± 5.53, and the mean age of control group was 19.63 ± 5.05. The left-hand 2D:4D ratios of AGA group (0.893 ± 0.267) were significantly lower than healthy controls (0.971 ± 0.028). No significant relationships were found between AGA severity, age of onset,and digit ratios.

Conclusions

The left-hand digit ratio 2D:4D is lower in AGA patients, and therefore, left-hand digit ratio 2D:4D can be used as an estimation tool for AGA development in future. There is not any correlation between digit ratio and age of onset. Also, there is no correlation between digit ratio 2D:4D and AGA severity.

http://ift.tt/2wgXvRm

ClinVar Is a Critical Resource to Advance Variant Interpretation

http://ift.tt/2wHZwa3

In Reply

http://ift.tt/2wmD4kb

Tumor Lysis Syndrome in Chronic Lymphocytic Leukemia with Novel Targeted Agents

AbstractTumor lysis syndrome (TLS) is an uncommon but potentially life‐threatening complication associated with the treatment of some cancers. If left untreated, TLS may result in acute renal failure, cardiac dysrhythmia, neurologic complications, seizures, or death. Tumor lysis syndrome is most commonly observed in patients with hematologic malignancies with a high proliferation rate undergoing treatment with very effective therapies. In chronic lymphocytic leukemia (CLL), historically, TLS has been observed less often, owing to a low proliferation rate and slow response to chemotherapy. New targeted therapies have recently been approved in the treatment of CLL, including the oral kinase inhibitors, idelalisib and ibrutinib, and the B‐cell lymphoma‐2 protein inhibitor, venetoclax. Several others are also under development, and combination strategies of these agents are being explored. This review examines the diagnosis, prevention, and management of TLS and summarizes the TLS experience in CLL clinical trials with newer targeted agents. Overall, the risk of TLS is small, but the consequences may be fatal; therefore, patients should be monitored carefully. Therapies capable of eliciting rapid response and combination regimens are increasingly being evaluated for treatment of CLL, which may pose a higher risk of TLS. For optimal management, patients at risk for TLS require prophylaxis and close monitoring with appropriate tests and appropriate management to correct laboratory abnormalities, which allows for safe and effective disease control.Implications for Practice.Tumor lysis syndrome (TLS) is a potentially fatal condition observed with hematologic malignancies, caused by release of cellular components in the bloodstream from rapidly dying tumor cells. The frequency and severity of TLS is partly dependent upon the biology of the disease and type of therapy administered. Novel targeted agents highly effective at inducing rapid cell death in chronic lymphocytic leukemia (CLL) may pose a risk for TLS in patients with tumors characterized by rapid growth, high tumor burden, and/or high sensitivity to treatment. In this review, prevention strategies and management of patients with CLL who develop TLS are described.

http://ift.tt/2wH5t7k

Finding Hope in Uncertain Times

http://ift.tt/2wmnDZj

PCAF/GCN5-Mediated Acetylation of RPA1 Promotes Nucleotide Excision Repair

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Meimei Zhao, Rui Geng, Xiang Guo, Ruoshi Yuan, Xiao Zhou, Yanyan Zhong, Yanfei Huo, Mei Zhou, Qinjian Shen, Yinglu Li, Weiguo Zhu, Jiadong Wang
The RPA complex can integrate multiple stress signals into diverse responses by activating distinct DNA repair pathways. However, it remains unclear how RPA1 elects to activate a specific repair pathway during different types of DNA damage. Here, we report that PCAF/GCN5-mediated K163 acetylation of RPA1 is crucial for nucleotide excision repair (NER) but is dispensable for other DNA repair pathways. Mechanistically, we demonstrate that the acetylation of RPA1 is critical for the steady accumulation of XPA at damaged DNA sites and preferentially activates the NER pathway. DNA-PK phosphorylates and activates PCAF upon UV damage and consequently promotes the acetylation of RPA1. Moreover, the acetylation of RPA1 is tightly regulated by HDAC6 and SIRT1. Together, our results demonstrate that the K163 acetylation of RPA1 plays a key role in the repair of UV-induced DNA damage and reveal how the specific RPA1 modification modulates the choice of distinct DNA repair pathways.

Graphical abstract

Teaser

RPA complex is a central player in multiple DNA repair pathways. Zhao et al. show that PCAF/GCN5-mediated acetylation of RPA1 is crucial for NER repair by promoting stable RPA1/XPA complex.


http://ift.tt/2xwujnW

UV-Induced RPA1 Acetylation Promotes Nucleotide Excision Repair

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Hanqing He, Jiajia Wang, Ting Liu
Replication protein A (RPA) is a multifunctional, single-stranded DNA-binding protein complex and plays a critical role in DNA replication and damage response. Herein, we show that the 70-kDa subunit of RPA (RPA1) is acetylated on lysine 163 by the acetyltransferases GCN5 and PCAF and that such acetylation is reversed principally via the action of the deacetylase HDAC6. UV irradiation promotes cytoplasmic translocation of HDAC6, thereby disrupting the interaction of HDAC6 with RPA1 and increasing RPA1 acetylation. Mutation of the acetylation site of RPA1 specifically impairs the ability of the protein to interact with the key nucleotide excision repair (NER) protein XPA, reduces XPA retention at sites of DNA damage caused by UV, compromises NER, and renders the cell hypersensitive to UV irradiation. Our data suggest that the acetylation status of RPA1 played a crucial role in repair of DNA damage via NER.

Graphical abstract

Teaser

He et al. find that the RPA1 protein becomes acetylated at lysine 163 in response to UV irradiation. Such acetylation specifically enhances interaction between RPA1 and the key NER protein XPA and promotes XPA retention at DNA damage sites. These findings suggest that RPA1 acetylation is a unique NER-related event.


http://ift.tt/2xwaKfA

Multilayered Reprogramming in Response to Persistent DNA Damage in C. elegans

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Diletta Edifizi, Hendrik Nolte, Vipin Babu, Laia Castells-Roca, Michael M. Mueller, Susanne Brodesser, Marcus Krüger, Björn Schumacher
DNA damage causally contributes to aging and age-related diseases. Mutations in nucleotide excision repair (NER) genes cause highly complex congenital syndromes characterized by growth retardation, cancer susceptibility, and accelerated aging in humans. Orthologous mutations in Caenorhabditis elegans lead to growth delay, genome instability, and accelerated functional decline, thus allowing investigation of the consequences of persistent DNA damage during development and aging in a simple metazoan model. Here, we conducted proteome, lipidome, and phosphoproteome analysis of NER-deficient animals in response to UV treatment to gain comprehensive insights into the full range of physiological adaptations to unrepaired DNA damage. We derive metabolic changes indicative of a tissue maintenance program and implicate an autophagy-mediated proteostatic response. We assign central roles for the insulin-, EGF-, and AMPK-like signaling pathways in orchestrating the adaptive response to DNA damage. Our results provide insights into the DNA damage responses in the organismal context.

Graphical abstract

Teaser

Edifizi et al. provide a comprehensive proteomics, phosphoproteomics, and lipidomics analysis of the response to persistent DNA damage in a metazoan organism. Proteostasis shifts toward autophagy, fatty acid metabolism is attenuated, and the insulin-, EGF-, and AMPK-like signaling pathways form the center of the response network.


http://ift.tt/2xw4LqY

NEIL3 Repairs Telomere Damage during S Phase to Secure Chromosome Segregation at Mitosis

Publication date: 29 August 2017
Source:Cell Reports, Volume 20, Issue 9
Author(s): Jia Zhou, Jany Chan, Marie Lambelé, Timur Yusufzai, Jason Stumpff, Patricia L. Opresko, Markus Thali, Susan S. Wallace
Oxidative damage to telomere DNA compromises telomere integrity. We recently reported that the DNA glycosylase NEIL3 preferentially repairs oxidative lesions in telomere sequences in vitro. Here, we show that loss of NEIL3 causes anaphase DNA bridging because of telomere dysfunction. NEIL3 expression increases during S phase and reaches maximal levels in late S/G2. NEIL3 co-localizes with TRF2 and associates with telomeres during S phase, and this association increases upon oxidative stress. Mechanistic studies reveal that NEIL3 binds to single-stranded DNA via its intrinsically disordered C terminus in a telomere-sequence-independent manner. Moreover, NEIL3 is recruited to telomeres through its interaction with TRF1, and this interaction enhances the enzymatic activity of purified NEIL3. Finally, we show that NEIL3 interacts with AP Endonuclease 1 (APE1) and the long-patch base excision repair proteins PCNA and FEN1. Taken together, we propose that NEIL3 protects genome stability through targeted repair of oxidative damage in telomeres during S/G2 phase.

Graphical abstract

Teaser

NEIL3 DNA glycosylase activity is critical in highly proliferating cells including cancer cells. Zhou et al. show that NEIL3 is specifically active at telomeres during S/G2, and that depletion of NEIL3 causes telomere dysfunction and thus mitotic defects, revealing its involvement in telomere repair, which prevents genome instability.


http://ift.tt/2xwegGN