The PTI-suppressing Avr2 effector from Fusarium oxysporum suppresses mono-ubiquitination and plasma membrane dissociation of BIK1

Plant pathogens use effector proteins to target host processes involved in pathogen perception, immune signalling, or defence outputs. Unlike foliar pathogens, it is poorly understood how root-invading pathogens suppress immunity. The Avr2 effector from the tomato root- and xylem-colonizing pathogen Fusarium oxysporum suppresses immune signalling induced by various pathogen-associated molecular patterns (PAMPs). It is unknown how Avr2 targets the immune system. Transgenic AVR2 Arabidopsis thaliana phenocopies mutants in which the pattern recognition receptor (PRR) co-receptor BRI1-ASSOCIATED RECEPTOR KINASE (BAK1) or its downstream signalling kinase BOTRYTIS-INDUCED KINASE 1 (BIK1) are knocked out. We therefore tested whether these kinases are Avr2 targets. Flg22-induced complex formation of the PRR FLAGELLIN SENSITIVE 2 and BAK1 occurred in the presence and absence of Avr2, indicating that Avr2 does not affect BAK1 function or PRR complex formation. Bimolecular fluorescence complementation assays showed that Avr2 and BIK1 co-localize in planta. Although Avr2 did not affect flg22-induced BIK1 phosphorylation, mono-ubiquitination was compromised. Furthermore, Avr2 affected BIK1 abundance and shifted its localization from nucleocytoplasmic to the cell periphery/plasma membrane. Together, these data imply that Avr2 may retain BIK1 at the plasma membrane, thereby suppressing its ability to activate immune signalling. Because mono-ubiquitination of BIK1 is required for its internalization, interference with this process by Avr2 could provide a mechanistic explanation for the compromised BIK1 mobility upon flg22 treatment. The identification of BIK1 as an effector target of a root-invading vascular pathogen identifies this kinase as a conserved signalling component for both root and shoot immunity

Comparing substance use outcomes by sexual identity among women: Differences using propensity score methods

Background: Differences in alcohol, tobacco, and other drug (ATOD) use by sexual identity vary across samples of women recruited using different sampling methods. We used propensity score (PS) weighting methods to address two methodological questions: (1) Do disparities between sexual minority women (SMW) and heterosexual women persist when differences in risk and protective factors are similarly distributed between groups, and (2) Does accounting for SMW-specific resiliency factors impact differences between non-probability samples of SMW? Methods: Four samples included SMW from a longitudinal study with a nonprobability sample (n = 373), a national general population panel sample (n = 373), and a national LGBTQ-specific panel sample (n = 311), as well as a national probability sample of heterosexual women (n = 446). Between-groups analyses using double-robust PS weighted models estimated differences in ATOD use under hypothetical conditions in which samples have similar risk and protective factors. Results: After PS weighting, imbalance in confounders between SMW and heterosexual samples was substantially reduced, but not eliminated. In double-robust PS weighted models, SMW samples consistently had significantly greater odds of drug use than heterosexuals, with odds from 8.8 to 5.6 times greater for frequent marijuana use and 4.8–3.2 greater for other drug use. Few differences between SMW samples in ATOD outcomes or other variables remained after PS weighting. Conclusion: Relative to heterosexual women, disparities in marijuana and other drug use among SMW are evident regardless of sampling strategy. The results provide some reassurance about the validity of large nonprobability samples, which remain an important recruitment strategy in research with SMW

Возможности фотодинамической терапии при эритроплазии Кейра

The review is dedicated to the analysis of the effectiveness of the treatment of erythroplasia of Queyrat (EQ) using photodynamic therapy (PDT). Particular attention is paid to the relationship between EQ and human papillomavirus (HPV) infection. The data of various researchers are presented, confirming the correlation between the development of the EQ and the HPV infection, however, it is noted that due to the small number of studies it is difficult to draw reliable conclusions on the presence and strength of this connection. The mechanisms of PDT involved in the implementation of both the antitumor effect in the treatment of EQ and the antiviral effect against HPV are considered. The data of 12 clinical studies and observations of the results of PDT of the EQ conducted in recent years are analyzed. An analysis of literature data showed that in the treatment of EQ, one of the two photosensitizers is usually used locally: 5-aminolevulinic acid or 5-aminolevulinic acid methyl ester. The treatment parameters in all the analyzed studies were similar: exposure to the ointment for 3–5 hours followed by irradiation with a light dose of 37–105 J/cm2. The number of PDT courses in different studies varied from 1 to 19. The effectiveness of treatment varied widely in different studies and clinical observations. Most studies have demonstrated high efficacy of PDT with complete regression in 36–83% (100% in one study) and a relapse-free follow-up period of up to 51 months. However, there were also individual clinical observations of patients in whom the treatment with the method of PDT was ineffective. It is possible that the described results were associated with improperly selected regimes of PDT or a large lesion area. Most authors especially note a very good cosmetic effect and a complete absence of scars after the treatment. Thus, PDT is an effective and promising method for the treatment of EQ that requires, however, a more thorough development of the application regimen and a deeper study of the antitumor and antiviral components of the mechanism of action.Обзор посвящен анализу эффективности лечения эритроплазии Кейра методом фотодинамической терапии (ФДТ). Особое внимание уделено вопросам взаимосвязи эритроплазии Кейра с инфицированием вирусом папилломы человека (ВПЧ). Приведены данные исследований, подтверждающие корреляцию между развитием заболевания и инфицированием ВПЧ, отмечено, что в связи с небольшим количеством исследований сложно делать достоверные выводы о наличии и силе этой связи. Рассмотрены механизмы ФДТ, участвующие в реализации как противоопухолевого эффекта при лечении эритроплазии Кейра, так и противовирусного действия в отношении ВПЧ. Проанализированы данные 12 клинических исследований и наблюдений результатов ФДТ при эритроплазии Кейра, проведенных в последние годы. Установлено, что при лечении заболевания, как правило, используют местно один из двух фотосенсибилизаторов: 5-аминолевулиновую кислоту (5-АЛК) или ее метиловый эфир. Параметры лечения во всех исследованиях были близки: экспозиция мази продолжительностью от 3 до 5 ч с последующим облучением со световой дозой 37 - 105 Дж/см2 . Количество курсов ФДТ в разных исследованиях составляло от 1 до 19. Эффективность лечения широко варьировала в разных исследованиях и клинических наблюдениях. Большинство исследований демонстрировало высокую эффективность ФДТ с полной регрессией образования в 36 - 83% наблюдений и продолжительностью безрецидивного периода до 51 мес. Имелись и отдельные клинические наблюдения, в которых ФДТ оказалась неэффективна. Возможно, описанные результаты были связаны с неправильно подобранными режимами ФДТ или большой площадью поражения. Большинство авторов отмечают хороший косметический эффект ФДТ и полное отсутствие рубцов после проведенного лечения. Таким образом, ФДТ является эффективным и перспективным методом лечения эритроплазии Кейра, однако, требующим тщательной отработки режимов применения и более глубокого изучения противоопухолевого и противовирусного компонентов механизма действия

Selective targeting of neuroblastoma tumour-initiating cells by compounds identified in stem cell-based small molecule screens

Neuroblastoma (NB) is the most deadly extra-cranial solid tumour in children necessitating an urgent need for effective and less toxic treatments. One reason for the lack of efficacious treatments may be the inability of existing drugs to target the tumour-initiating or cancer stem cell population responsible for sustaining tumour growth, metastases and relapse. Here, we describe a strategy to identify compounds that selectively target patient-derived cancer stem cell-like tumour-initiating cells (TICs) while sparing normal paediatric stem cells (skin-derived precursors, SKPs) and characterize two therapeutic candidates. DECA-14 and rapamycin were identified as NB TIC-selective agents. Both compounds induced TIC death at nanomolar concentrations in vitro, significantly reduced NB xenograft tumour weight in vivo, and dramatically decreased self-renewal or tumour-initiation capacity in treated tumours. These results demonstrate that differential drug sensitivities between TICs and normal paediatric stem cells can be exploited to identify novel, patient-specific and potentially less toxic therapies

Supercapacitance from cellulose and carbon nanotube nanocomposite fibers

Copyright © 2013 American Chemical SocietyACS AuthorChoice open access articleMultiwalled carbon nanotube (MWNT)/cellulose composite nanofibers have been prepared by electrospinning a MWNT/cellulose acetate blend solution followed by deacetylation. These composite nanofibers were then used as precursors for carbon nanofibers (CNFs). The effect of nanotubes on the stabilization of the precursor and microstructure of the resultant CNFs were investigated using thermogravimetric analysis, transmission electron microscopy and Raman spectroscopy. It is demonstrated that the incorporated MWNTs reduce the activation energy of the oxidative stabilization of cellulose nanofibers from 230 to 180 kJ mol–1. They also increase the crystallite size, structural order, and electrical conductivity of the activated CNFs (ACNFs). The surface area of the ACNFs increased upon addition of nanotubes which protrude from the fiber leading to a rougher surface. The ACNFs were used as the electrodes of a supercapacitor. The electrochemical capacitance of the ACNF derived from pure cellulose nanofibers is demonstrated to be 105 F g–1 at a current density of 10 A g–1, which increases to 145 F g–1 upon the addition of 6% of MWNTs.The authors would like to thank the [Engineering and Physical Sciences Research Council] EPSRC (EP/F036914/1 and EP/I023879/1), Guangdong and Shenzhen Innovative Research Team Program (No. 2011D052,KYPT20121228160843692), National Natural Science Foundation of China (Grant No. 21201175), R&D Funds for basic Research Program of Shenzhen (Grant No. JCYJ20120615140007998), and the Universities of Exeter and Manchester for funding this research

Near-field polarization measurements based on two arbitrary, orthogonal optical field components

Using a multi-heterodyne scanning near-field optical microscope, we detect two arbitrary, orthogonal components of the near field. A numerical treatment of the experimental data allows the retrieval of the transverse and longitudinal components of the modes propagating in a waveguide for Bloch surface waves

Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described

Genetic Diversity of the ORF5 Gene of Porcine Reproductive and Respiratory Syndrome Virus Isolates in Southwest China from 2007 to 2009

To gain insight into the molecular epidemiology and possible mechanisms of genetic variation of porcine reproductive and respiratory syndrome (PRRS) in Yunnan Province of China, the ORF5 gene of 32 PRRSV isolates from clinical samples collected from 2007 to 2009 were sequenced and analyzed. Nucleotide and amino acid analyses were carried out on 32 isolates and representative strains of the North American genotype, European genotype and two representative Chinese isolates. Results revealed that these isolates share 86.9–99.0% nucleotide and 87.5–98.0% amino acid identity with VR-2332 the prototypical North American PRRSV, 61.7–62.9% and 54.3–57.8% with Lelystad virus (LV) the representative strain of European genotype, 91.2–95.4% and 90.0–94.5% with CH-1a that was isolated in mainland China in 1996, 88.1–99.3% and 85.5–99.0% with JX-A1 the representative strain of High pathogenic PRRSV in China, and 86.2–99.8% and 85.5–100.0% between isolated strains of different years, respectively. Phylogenetic analysis revealed that all 32 PRRSV isolates belonged to the North American genotype and were further divided into two different subgenotypes. Subgenotype 1 comprised twenty two Yunnan isolates which divided into two branches. Subgenotype 2 comprised ten isolates which closely related to the RespPRRS vaccine and its parent strain VR-2332. The functional domains of GP5 such as the signal peptide, ectodomain, transmembrane regions and endodomain were identified and some motifs in GP5 with known functions, such as primary neutralizing epitope (PNE) and decoy epitope were also further analyzed. Our study shown the great genetic diversity of PRRSV in southwest China, rendering the guide for control and prevention of this disease