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Stuart K Gardiner, Steven L Mansberger
Purpose: We have previously shown that sensitivities obtained at severely damaged visual field locations (<15-19 dB) are unreliable and highly variable. This study evaluates a testing algorithm that does not present very high contrast stimuli in damaged locations above approximately 1000% contrast, but instead concentrates on more precise estimation at remaining locations. Methods: A trained ophthalmic technician tested 36 eyes of 36 participants twice with each of two different testing algorithms: ZEST0, which allowed sensitivities within the range 0 to 35 dB, and ZEST15, which allowed sensitivities between 15 and 35 dB but was otherwise identical...
October 1, 2016: Investigative Ophthalmology & Visual Science
Judd F Hultquist, Kathrin Schumann, Jonathan M Woo, Lara Manganaro, Michael J McGregor, Jennifer Doudna, Viviana Simon, Nevan J Krogan, Alexander Marson
New genetic tools are needed to understand the functional interactions between HIV and human host factors in primary cells. We recently developed a method to edit the genome of primary CD4(+) T cells by electroporation of CRISPR/Cas9 ribonucleoproteins (RNPs). Here, we adapted this methodology to a high-throughput platform for the efficient, arrayed editing of candidate host factors. CXCR4 or CCR5 knockout cells generated with this method are resistant to HIV infection in a tropism-dependent manner, whereas knockout of LEDGF or TNPO3 results in a tropism-independent reduction in infection...
October 25, 2016: Cell Reports
Dror Alishekevitz, Svetlana Gingis-Velitski, Orit Kaidar-Person, Lilach Gutter-Kapon, Sandra D Scherer, Ziv Raviv, Emmanuelle Merquiol, Yael Ben-Nun, Valeria Miller, Chen Rachman-Tzemah, Michael Timaner, Yelena Mumblat, Neta Ilan, David Loven, Dov Hershkovitz, Ronit Satchi-Fainaro, Galia Blum, Jonathan P Sleeman, Israel Vlodavsky, Yuval Shaked
While chemotherapy strongly restricts or reverses tumor growth, the response of host tissue to therapy can counteract its anti-tumor activity by promoting tumor re-growth and/or metastases, thus limiting therapeutic efficacy. Here, we show that vascular endothelial growth factor receptor 3 (VEGFR3)-expressing macrophages infiltrating chemotherapy-treated tumors play a significant role in metastasis. They do so in part by inducing lymphangiogenesis as a result of cathepsin release, leading to VEGF-C upregulation by heparanase...
October 25, 2016: Cell Reports
Nuno Miguel Luis, Lifen Wang, Mauricio Ortega, Hansong Deng, Subhash D Katewa, Patrick Wai-Lun Li, Jason Karpac, Heinrich Jasper, Pankaj Kapahi
Dietary restriction (DR) is one of the most robust lifespan-extending interventions in animals. The beneficial effects of DR involve a metabolic adaptation toward increased triglyceride usage. The regulatory mechanism and the tissue specificity of this metabolic switch remain unclear. Here, we show that the IRE1/XBP1 endoplasmic reticulum (ER) stress signaling module mediates metabolic adaptation upon DR in flies by promoting triglyceride synthesis and accumulation in enterocytes (ECs) of the Drosophila midgut...
October 25, 2016: Cell Reports
Mohammed Badrul Amin, Naoyuki Miura, Mohammad Khaja Mafij Uddin, Mohammod Johirul Islam, Nobuaki Yoshida, Sachiko Iseki, Tsutomu Kume, Paul Trainor, Hirotomo Saitsu, Kazushi Aoto
Foxc2, a member of the winged helix transcription factor family, is essential for eye, calvarial bone, cardiovascular and kidney development in mice. Nevertheless, how Foxc2-expressing cells and their descendent cells contribute to the development of these tissues and organs has not been elucidated. Here, we generated a Foxc2 knock-in (Foxc2(CreERT2) ) mouse, in which administration of estrogen receptor antagonist tamoxifen induces nuclear translocation of Cre recombinase in Foxc2-expressing cells. By crossing with ROSA-LacZ reporter mice (Foxc2(CreERT2) ; R26R), the fate of Foxc2 positive (Foxc2(+) ) cells was analyzed through LacZ staining at various embryonic stages...
October 26, 2016: Congenital Anomalies
Nobuaki Suzuki, Shoichi Hazama, Haruo Iguchi, Kazuhiro Uesugi, Hiroaki Tanaka, Kosei Hirakawa, Atsushi Aruga, Takashi Hatori, Hidenobu Ishizaki, Yuzo Umeda, Toshiyoshi Fujiwara, Tetsuya Ikemoto, Mitsuo Shimada, Kazuhiko Yoshimatsu, Ryoichi Shimizu, Hiroto Hayashi, Koichiro Sakata, Hiroko Takenouchi, Hiroto Matsui, Yoshitaro Shindo, Michihisa Iida, Yasunobu Koki, Hideki Arima, Hiroyuki Furukawa, Tomio Ueno, Shigefumi Yoshino, Yusuke Nakamura, Masaaki Oka, Hiroaki Nagano
We previously conducted a phase I clinical trial combining the HLA-A*2402-restricted KIF20A-derived peptide vaccine with gemcitabine for advanced pancreatic cancer (PC) and confirmed its safety and immunogenicity in cancer patients. In this study, we conducted a multicenter, single-armed, phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide. We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine...
October 26, 2016: Cancer Science
Mariana Angélica Peixoto de Souza, Jane Fonseca Dias, Fabiane Ribeiro Ferreira, Marisa Cotta Mancini, Renata Noce Kirkwood, Rosana Ferreira Sampaio
The cross sectional study aims to create the patients' profile and understand their demands for seeking public rehabilitation services from Belo Horizonte. Data were analyzed from 516 patients who gained entry into the health care system by means of the Protocol for Identification of Problems for Rehabilitation (PLPR). It allows for gathering information related to one's health and the social context, including a brief functional description (BFD) with 25 items. Most patients were females, mean age of 57 years, and 54% declared to be responsible for the family income...
October 2016: Ciência & Saúde Coletiva
Wederson Santos
This article discusses the main advances and challenges for understanding and evaluating disability as a restriction for social participation. This new understanding has its origins in the 2006 WHO International Classification of Functioning, Disability, and Health - ICF, the 2001 UN Convention on the Rights of Persons with Disabilities, and more recently, the July 2015 Brazilian Inclusion of People with Disabilities Act (IPDA), also known as the Statute on Persons with Disabilities. The change in the understanding of disability from a merely biomedical perspective, to an understanding that is based on oppression and social inequality reinforces the idea that disability is not an individual attribute, but the result of a society that is not prepared for human diversity...
October 2016: Ciência & Saúde Coletiva
Sérgio Ferreira de Lima, Mayara Mansur Fernandes Tavares, Jamilly Lopes de Macedo, Renata Santos de Oliveira, Sandra de Andrade Heráclio, Maria de Mascena Diniz Maia, Paulo Roberto Eleutério de Souza, Ronald Moura, Sergio Crovella
Human papillomavirus (HPV) infections are strongly associated with the development of cervical intraepithelial neoplasias and invasive cervical cancer. Polymorphisms in cytokine-encoding genes and behavioural cofactors could play an important role in protecting an individual against viral infections and cancer. Here, we investigated whether IL-6 -174 G>C, IL-8 +396 G>T, and TGF-β1 +869 G>C and +915 G>C polymorphisms were associated with susceptibility to HPV infection in women from north-east (Pernambuco) Brazil...
October 24, 2016: Memórias do Instituto Oswaldo Cruz
Sarah E Baum, Kari White, Kristine Hopkins, Joseph E Potter, Daniel Grossman
BACKGROUND: In November 2013, Texas implemented three abortion restrictions included in House Bill 2 (HB 2). Within six months, the number of facilities providing abortion decreased by almost half, and the remaining facilities were concentrated in large urban centers. The number of medication abortions decreased by 70% compared to the same period one year prior due to restrictions on this method imposed by HB 2. The purpose of this study was to explore qualitatively the experiences of women who were most affected by the law: those who had to travel farther to reach a facility and those desiring medication abortion...
2016: PloS One
Denise F R Rawcliffe, Lennart Österman, Hans Lindsten, Monica Holmberg
Hereditary myopathy with lactic acidosis (HML) is an autosomal recessive disease caused by an intronic one-base mutation in the iron-sulfur cluster assembly (ISCU) gene, resulting in aberrant splicing. The incorrectly spliced transcripts contain a 100 or 86 bp intron sequence encoding a non-functional ISCU protein, which leads to defects in several Fe-S containing proteins in the respiratory chain and the TCA cycle. The symptoms in HML are restricted to skeletal muscle, and it has been proposed that this effect is due to higher levels of incorrectly spliced ISCU in skeletal muscle compared with other energy-demanding tissues...
2016: PloS One
Jonathan D Hibshman, Anthony Hung, L Ryan Baugh
Maternal effects of environmental conditions produce intergenerational phenotypic plasticity. Adaptive value of these effects depends on appropriate anticipation of environmental conditions in the next generation, and mismatch between conditions may contribute to disease. However, regulation of intergenerational plasticity is poorly understood. Dietary restriction (DR) delays aging but maternal effects have not been investigated. We demonstrate maternal effects of DR in the roundworm C. elegans. Worms cultured in DR produce fewer but larger progeny...
October 2016: PLoS Genetics
Ljerka Lah, Daronja Trense, Harald Benke, Per Berggren, Þorvaldur Gunnlaugsson, Christina Lockyer, Ayaka Öztürk, Bayram Öztürk, Iwona Pawliczka, Anna Roos, Ursula Siebert, Krzysztof Skóra, Gísli Víkingsson, Ralph Tiedemann
The population structure of the highly mobile marine mammal, the harbor porpoise (Phocoena phocoena), in the Atlantic shelf waters follows a pattern of significant isolation-by-distance. The population structure of harbor porpoises from the Baltic Sea, which is connected with the North Sea through a series of basins separated by shallow underwater ridges, however, is more complex. Here, we investigated the population differentiation of harbor porpoises in European Seas with a special focus on the Baltic Sea and adjacent waters, using a population genomics approach...
2016: PloS One
Yongmin Zhang, Shuang Guo, Wentao Wu, Zhirong Qin, Xuefeng Liu
Herein, we describe a strategy of fabricating CO2-triggered oil-in-water Pickering emulsion based on silica nanoparticles func-tionalized in situ by a trace amount of conventional CO2-switchable surfactant, N-(3-(dimethylamino)propyl)alkyl amide (CnPMA). By alternately bubbling CO2 and N2 at a moderate conditions (30 oC, 80 mL·min-1), silica nanoparticles reversibly switch between amphipathic and hydrophilic as a result of the adsorption of ammonium (CO2) and the desorption of ter-tiary amine (N2). The emulsion can then be smart switched "on (stable)" and "off (unstable)," along with homogenization, without needing cooling and heating...
October 26, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
G Sybren de Hoog, Karolina Dukik, Michel Monod, Ann Packeu, Dirk Stubbe, Marijke Hendrickx, Christiane Kupsch, J Benjamin Stielow, Joanna Freeke, Markus Göker, Ali Rezaei-Matehkolaei, Hossein Mirhendi, Yvonne Gräser
Type and reference strains of members of the onygenalean family Arthrodermataceae have been sequenced for rDNA ITS and partial LSU, the ribosomal 60S protein, and fragments of β-tubulin and translation elongation factor 3. The resulting phylogenetic trees showed a large degree of correspondence, and topologies matched those of earlier published phylogenies demonstrating that the phylogenetic representation of dermatophytes and dermatophyte-like fungi has reached an acceptable level of stability. All trees showed Trichophyton to be polyphyletic...
October 25, 2016: Mycopathologia
Roberto Nuño Solinís, Patricia Arratibel Ugarte, Ander Rojo, Yuri Sanchez Gonzalez
INTRODUCTION: The goal of chronic hepatitis C (CHC) treatment is to achieve a sustained virologic response (SVR). The new generation of direct-acting antivirals (DAAs) offers 90-100% SVR rates. However, access to these treatments is generally limited to patients with advanced liver disease. The aim of this review is to provide an overview of the clinical and economic benefits of achieving SVR and to better understand the full value of CHC treatment in all stages of liver disease. METHODS: A comprehensive literature review was performed using the PubMed, Embase, and Cochrane library databases to identify articles examining the clinical, economic, and quality of life benefits associated with SVR...
October 25, 2016: Infectious Diseases and Therapy
Christiane Stern, Laurent Castera
Non-invasive diagnosis and quantification of hepatic steatosis rely on two different but complementary approaches: biomarkers or imaging techniques, either ultrasound-based such as liver ultrasonography and controlled attenuation parameter (CAP), or computed tomography (CT) and magnetic resonance imaging (MRI). Scores for the detection of steatosis have not gained much popularity in clinical practice so far. CAP, using the M probe, is the most promising technique but needs to be implemented with the XL probe and compared to ultrasound that, despite its limitations, remains the most widely used method...
October 25, 2016: Hepatology International
Clement Cochain, Alma Zernecke
Although infiltration of CD8(+) T cells in human atherosclerotic lesions has been described 30 years ago, the role of these cells in lesion development has long remained enigmatic. While experimental models hinted at their pro-atherogenic role based on circumstantial evidence, genetic mouse models of cytotoxic CD8(+) T cell-specific immune deficiency suggested no crucial role of these cells in lesion development. However, in recent years, more refined models of adoptive cell transfer, disruption of specific immune regulatory pathways or monoclonal antibody-mediated cell depletion have proposed both atheroprotective and pro-atherogenic functions for CD8(+) T cells in atherosclerosis...
November 2016: Basic Research in Cardiology
Salem A Beshyah, Ibrahim H Sherif, Farida Chentli, Amir Hamrahian, Aly B Khalil, Hussein Raef, Mohamed El-Fikki, Selim Jambart
BACKGROUND: Prolactinomas are the commonest functional tumors of the pituitary gland. There are still controversies regarding medical therapy in specific clinical situations. Patients may be managed by different specialists in the Middle East and North Africa (MENA) region and no data exist on patterns of clinical management. OBJECTIVES: To ascertain the diagnostic and therapeutic approaches to prolactinomas among relevant professionals from the MENA region. METHODS: An online survey of a large sample of physicians was conducted...
October 25, 2016: Pituitary
Mohammad Abass Ahanger, R M Agarwal
Pot experiments were conducted to find out the effectivity of K on Triticum aestivum L cultivars. Polyethylene glycol 6000 (PEG 6000) was used as an osmoticum to induce osmotic stress under sand culture setting up the water potential of external solution at -3 and -5 bars. In pots, plants were raised under restricted and normal irrigation and K was applied in varying doses (0, 20, 40, 60 kg ha(-1)) and estimation of different physiological and biochemical parameters was done at two developmental stages, i...
October 25, 2016: Protoplasma
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