Mechanisms of copper stress alleviation in Citrus trees after metal uptake by leaves or roots

Abstract

Nutritional disorders caused by copper (Cu) have affected citrus orchards. Since Cu is foliar sprayed as a pesticide to control citrus diseases, this metal accumulates in the soil. Thereby, we evaluated the effects of Cu leaf absorption after spray of different metal sources, as well as roots absorption on growth, nutritional status, and oxidative stress of young sweet orange trees. Two experiments were carried out under greenhouse conditions. The first experiment was set up with varying Cu levels to the soil (nil Cu, 0.5, 2.0, 4.0 and 8.0 g of Cu per plant as CuSO₄.5H₂O), whereas the second experiment with Cu application via foliar sprays (0.5 and 2.0 g of Cu per plant) and comparing two metal sources (CuSO₄.5H₂O or Cu(OH)₂). Copper was mainly accumulated in roots with soil supply, but an increase of oxidative stress levels was observed in leaves. On the other hand, Cu concentrations were higher in leaves that received foliar sprays, mainly as Cu(OH)₂. However, when sulfate was foliar sprayed, plants exhibited more symptoms of injuries in the canopy with decreased chlorophyll contents and increased hydrogen peroxide and lipid peroxidation levels. Copper toxicity was characterized by sap leakage from the trunk and twigs, which is the first report of this specific Cu excess symptom in woody trees. Despite plants with 8.0 g of Cu soil-applied exhibiting the sap leakage, growth of new plant parts was more vigorous with lower oxidative stress levels and injuries compared to those with 4.0 g of Cu soil-applied (without sap leakage). With the highest level of Cu applied via foliar as sulfate, Cu was eliminated by plant roots, increasing the rhizospheric soil metal levels. Despite citrus likely exhibiting different mechanisms to reduce the damages caused by metal toxicity, such as responsive enzymatic antioxidant system, metal accumulation in the roots, and metal exclusion by roots, excess Cu resulted in damages on plant growth and metabolism when the metal was taken up either by roots or leaves.

http://ift.tt/2oAWrCN

Synthesis and Biological Evaluation of Histone Deacetylase and DNA Topoisomerase II-Targeted Inhibitors

Publication date: Available online 27 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Mitsuaki Yamashita, Teruyuki Tahara, Shinya Hayakawa, Hironobu Matsumoto, Shun-ichi Wada, Kiyoshi Tomioka, Akira Iida
HDAC inhibitors enable histones to maintain a high degree of acetylation. The resulting looser state of chromatin DNA may increase the accessibility of DNA drug targets and consequently improve the efficiency of anticancer drugs targeting DNA, such as Topo II inhibitors. A novel class of nucleoside-SAHA derivatives has been designed and synthesized based on the synergistic antitumor effects of topoisomerase II and histone deacetylase inhibitors. Their inhibitory activities toward histone deacetylases and Topo II, and their cytotoxicities in cancer cell lines, were evaluated. Among the synthesized hybrid compounds, compound 16b showed the potent HDAC inhibitory activity at a low nanomolar level and exhibited antiproliferative activity toward cancer cell lines including MCF-7 (breast), HCT-116 (colon), and DU-145 (prostate) cancer cells at a low micromolar level. Moreover, compound 16a showed HDAC6-selectivity 20-fold over HDAC1.

Graphical abstract

http://ift.tt/2CKYWYj

Discovery and optimization of piperazine-1-thiourea-based human phosphoglycerate dehydrogenase inhibitors

Publication date: Available online 27 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Jason M. Rohde, Kyle R. Brimacombe, Li Liu, Michael E. Pacold, Adam Yasgar, Dorian M. Cheff, Tobie D. Lee, Ganesha Rai, Bolormaa Baljinnyam, Zhuyin Li, Anton Simeonov, Matthew D. Hall, Min Shen, David M. Sabatini, Matthew B. Boxer
Proliferating cells, including cancer cells, obtain serine both exogenously and via the metabolism of glucose. By catalyzing the first, rate-limiting step in the synthesis of serine from glucose, phosphoglycerate dehydrogenase (PHGDH) controls flux through the biosynthetic pathway for this important amino acid and represents a putative target in oncology. To discover inhibitors of PHGDH, a coupled biochemical assay was developed and optimized to enable high-throughput screening for inhibitors of human PHGDH. Feedback inhibition was minimized by coupling PHGDH activity to two downstream enzymes (PSAT1 and PSPH), providing a marked improvement in enzymatic turnover. Further coupling of NADH to a diaphorase/resazurin system enabled a red-shifted detection readout, minimizing interference due to compound autofluorescence. With this protocol, over 400,000 small molecules were screened for PHGDH inhibition, and following hit validation and triage work, a piperazine-1-thiourea was identified. Following rounds of medicinal chemistry and SAR exploration, two probes (NCT-502 and NCT-503) were identified. These molecules demonstrated improved target activity and encouraging ADME properties, enabling in vitro assessment of the biological importance of PHGDH, and its role in the fate of serine in PHGDH-dependent cancer cells. This manuscript reports the assay development and medicinal chemistry leading to the development of NCT-502 and -503 reported in Nat. Chem. Biol.2016,12 (6), 452-8.

Graphical abstract

http://ift.tt/2ow02Tz

Studies on Non-Steroidal Inhibitors of Aromatase Enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole Derivatives

Publication date: Available online 27 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Zafer Şahin, Merve Ertaş, Barkın Berk, Sevde Nur Biltekin, Leyla Yurttaş, Şeref Demirayak
Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects.Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition.In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC50:0.42nM). Then, their antiproliferative activity over MCF-7 and HEK cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.

Graphical abstract

http://ift.tt/2CMRbRx

Immunomodulation as Rescue for Chronic Atonic Skin Wounds

Publication date: Available online 27 February 2018
Source:Trends in Immunology
Author(s): Ghislain Opdenakker, Jo Van Damme, Jan Jeroen Vranckx
Chronic skin wounds, caused by arterial or venous insufficiency or by physical pressure, constitute an increasing medical problem as populations age. Whereas typical wounds are characterized by local inflammation that participates in the healing process, atonic wounds lack inflammatory markers, such as neutrophil infiltration, and generally do not heal. Recently, prominent roles in the immunopathology of chronic wounds were attributed to dysregulations in specific cytokines, chemokines, matrix metalloproteinases (MMPs), and their substrates. Together with the complement system, these molecular players provide necessary defense against infections, initiate angiogenesis, and prepare tissue reconstitution. Here, we review the current state of the field and include the concept that, aside from surgery and stem cell therapy, healing may be enhanced by immunomodulating agents.



http://ift.tt/2GQ7u2t

Surface electromyography can quantify temporal and spatial patterns of activation of intrinsic human foot muscles

Publication date: Available online 27 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): E. Ferrari, G. Cooper, N.D. Reeves, E.F. Hodson-Tole
Intrinsic foot muscles (IFM) are a crucial component within the human foot. Investigating their functioning can help understand healthy and pathological behaviour of foot and ankle, fundamental for everyday activities. Recording muscle activation from IFM has been attempted with invasive techniques, mainly investigating single muscles. Here we present a novel methodology, to investigate the feasibility of recording physiological surface EMG (sEMG) non-invasively and quantify patterns of activation across the whole plantar region of the foot. sEMG were recorded with a 13×5 array from the sole of the foot (n=25) during two-foot stance, two-foot tiptoe and anterior/posterior sways. Physiological features of sEMG were analysed. During anterior/posterior epochs within the sway task, sEMG patterns were analysed in terms of signal amplitude (intensity) and structure (Sample Entropy) distribution, by evaluating the centre of gravity (CoG) of each topographical map. Results suggest signals are physiological and not affected by loading. Both amplitude and sample entropy CoG coordinates were grouped in one region and overlapped, suggesting that the region with highest amplitude corresponds with the most predictable signal. Therefore, both spatial and temporal features of IFM activation may be recorded non-invasively, providing opportunity for more detailed investigation of IFM function in healthy and patient populations.



http://ift.tt/2oBe0mh

Role of novel synbiotic supplementation on ovalbumin induced allergy model: Impact on immunemodulation

Publication date: Available online 27 February 2018
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Himaja Nallagatla, R Hemalatha, MV Surekha, Mohd Shujauddin
This study aimed to determine effect of a novel synbiotic formulated from green gram on allergen induced immune response. BALB/c mice (F0 generation) were supplemented with saline, Lactobacillus rhamnosus GG (LGG) or synbiotic. The supplementation was continued throughout gestation and lactation. F1 generation pups also received respective supplementations as their mothers and were designated as postweaning probiotic and synbiotic groups. At the age of 60 days, OVA (allergen) sensitization was induced in F1 pups and various immune parameters were determined. As expected, OVA sensitized pups (F1 Ova+) developed chronic interstitial pneumonitis (CIP), with positive passive cutaneous anaphylaxis (PCA) reaction, increased (p<0.05) specific and total IgG and IgE concentration along with higher (p<0.05) allergenic IL-5 value (283.6 ± 11.8pg/ml). Synbiotic supplementation among the offspring showed better protection against allergy in the pups, as observed by absence of CIP, negative PCA reaction and reduced (p<0.05) IL-5 concentration (37.8 ± 2.42pg/ml) compared to F1 Ova+ group. Probiotic supplementation showed similar protection from allergy although, synbiotic scored better as immunemodulator. Synbiotic treatment improved T-regulatory cells percentage by 4-fold whereas probiotic supplementation improved it by 3-fold compared to control. Synbiotic group had enhanced production of IL-10, TGF-β (p<0.05) by 11.6-fold and 4-fold respectively, while probiotic group registered 9-fold and 3.65-fold increase respectively. Similarly, allergen specific IgG and IgE concentration reduced by 1.9 and 1.7-folds with synbiotic and probiotic supplementations respectively. In conclusion, synbiotic group scored better in preventing ovalbumin induced allergy compared to probiotic group among offspring when supplemented prenatally and postweaning.

Graphical abstract

http://ift.tt/2Cr5RdB

An Unusual Polypoid Symptomatic Carotid Plaque

Publication date: Available online 27 February 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Stephen C. Crockett, Matthew Metcalfe




http://ift.tt/2oAeyst

Scholar : These new articles for Amyloid are available online

The online platform for Taylor & Francis Online content New for Amyloid and online now on Taylor & Francis Online: Original Article Bone marrow plasma cell infiltration in light chain amyloidosis: impact on organ involvement and outcome Natalia Tovar, Luis Gerardo Rodríguez-Lobato, Maria Teresa Cibeira, Laura Magnano, Ignacio Isola, Laura Rosiñol, Joan Bladé & Carlos Fernández de Larrea Pages: 1-7 | DOI: 10.1080/13506129.2018.1443439 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) 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 Studies in Chinese Religions are available online

The online platform for Taylor & Francis Online content New for Studies in Chinese Religions and online now on Taylor & Francis Online: Article 'Circles of light' and 'treasure ships' in the Visualizing Amitāyus Tableaux: with a focus on some cases in Sichuan from the Tang and Five Dynasties period Mingli Sun Pages: 1-39 | DOI: 10.1080/23729988.2018.1429144 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. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) 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 Comedy Studies are available online

The online platform for Taylor & Francis Online content New for Comedy Studies and online now on Taylor & Francis Online: Original Articles Reports of the death of British theatrical comedy? Greatly exaggerated or sadly accurate? Lloyd Peters Pages: 1-8 | DOI: 10.1080/2040610X.2018.1437166 To update which email alerts you receive, manage your alerts within the My Account area. Unsubscribe from new content alerts for this journal (both new issue and latest article notifications) 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 state of testosterone therapy since the fda's 2015 labeling changes: indications and cardiovascular risk

Summary

Objective

A label change for testosterone (T) products in March 2015 followed a highly-publicized FDA advisory committee meeting in September 2014. Changes included a warning of possible increased cardiovascular (CV) risks and restriction of indicated populations to younger men with a limited set of known etiologies of testosterone deficiency (TD). These changes greatly impacted clinical practice and public perception of T therapy (TTh). Our aim was to review these changes in light of subsequently published studies.

Design

We identified 23 studies through June 2017, including 12 clinical trials and 11 observational studies. The Testosterone Trials included 790 men 65y and older with TD without known etiology, assigned to 1y T gel or placebo.

Results

Demonstrated benefits of T included sexual activity and desire, physical activity, and mood. There were 9 major adverse CV events (MACE) in the T arm and 16 in the placebo arm. No study reported increased MACE with TTh. A 3y RCT showed no difference in carotid atherosclerosis. Several large observational studies reported reduced CV events with TTh, including one showing progressively reduced CV and mortality risk with greater duration of TTh. Men whose serum T normalized with TTh had reduced risk of MI and death compared with men whose T levels failed to normalize.

Conclusion

We conclude that existing evidence fails to support increased CV risk with TTh; on the contrary, there is evidence suggestive of real-world CV benefits. Finally, existing evidence provides benefits of TTh in older men without known etiology for T deficiency.

This article is protected by copyright. All rights reserved.

http://ift.tt/2ot4WAy

The role of the motor system in action naming in patients with neurodegenerative extrapyramidal syndromes

Publication date: March 2018
Source:Cortex, Volume 100
Author(s): Maria Cotelli, Rosa Manenti, Michela Brambilla, Barbara Borroni
Previous studies of patients with brain damage have suggested a close relationship between aphasia and movement disorders. Neurodegenerative extrapyramidal syndromes associated with cognitive impairment provide an interesting model for studying the neural substrates of cognitive and motor symptoms.In this review, we focused on studies investigating language production abilities in patients with Parkinson's disease (PD), Corticobasal Syndrome (CBS) and Progressive Supranuclear Palsy (PSP). According to some reports, these patients exhibit a reduction in performance in both action and object naming or verb production compared to healthy individuals. Furthermore, a disproportional impairment of action naming compared to object naming was systematically observed in patients with these disorders.The study of these clinical conditions offers the unique opportunity to examine the close link between linguistic features and motor characteristics of action. This particular pattern of language impairment may contribute to the debate on embodiment theory and on the involvement of the basal ganglia in language and in integrating language and movement.From a translational perspective, we suggest that language ability assessments are useful in the clinical work-up, along with neuropsychological and motor evaluations. Specific protocols should be developed in the near future to better characterize language deficits and to permit an early cognitive diagnosis. Moreover, the link between language deficits and motor impairment opens a new issue for treatment approaches. Treatment of one of these two symptoms may ameliorate the other, and treating both may produce a greater improvement in patients' global clinical conditions.



http://ift.tt/2CLX55z

Visual Mental Imagery: A View from Artificial Intelligence

Publication date: Available online 27 February 2018
Source:Cortex
Author(s): Maithilee Kunda
This article investigates whether, and how, an artificial intelligence (AI) system can be said to use visual, imagery-based representations in a way that is analogous to the use of visual mental imagery by people. In particular, this article aims to answer two fundamental questions about imagery-based AI systems. First, what might visual imagery look like in an AI system, in terms of the internal representations used by the system to store and reason about knowledge? Second, what kinds of intelligent tasks would an imagery-based AI system be able to accomplish? The first question is answered by providing a working definition of what constitutes an imagery-based knowledge representation, and the second question is answered through a literature survey of imagery-based AI systems that have been developed over the past several decades of AI research, spanning task domains of: 1) template-based visual search; 2) spatial and diagrammatic reasoning; 3) geometric analogies and matrix reasoning; 4) naive physics; and 5) commonsense reasoning for question answering. This article concludes by discussing three important open research questions in the study of visual-imagery-based AI systems—on evaluating system performance, learning imagery operators, and representing abstract concepts—and their implications for understanding human visual mental imagery.



http://ift.tt/2ousswV

Cover Figure

Publication date: March 2018
Source:Cortex, Volume 100





http://ift.tt/2CMzUIb

Editorial Board

Publication date: March 2018
Source:Cortex, Volume 100





http://ift.tt/2FbcVfe

Looking but not seeing: Increased eye fixations in behavioural-variant frontotemporal dementia

Publication date: Available online 27 February 2018
Source:Cortex
Author(s): Rosalind Hutchings, Romina Palermo, Jason Bruggemann, John R. Hodges, Olivier Piguet, Fiona Kumfor
Face processing plays a central role in human communication, with the eye region a particularly important cue for discriminating emotions. Indeed, reduced attention to the eyes has been argued to underlie social deficits in a number of clinical populations. Despite well-established impairments in facial affect recognition in behavioural-variant frontotemporal dementia, whether these patients also have perturbed facial scanning is yet to be investigated. The current study employed eye tracking to record visual scanning of faces in 20 behavioural-variant frontotemporal dementia patients and 21 controls. Remarkably, behavioural-variant frontotemporal dementia patients displayed more fixations to the eyes of emotional faces, compared to controls. Neural regions associated with fixations to the eyes included the left inferior frontal gyrus, right cerebellum and middle temporal gyrus. Our study is the first to show such compensatory functions in behavioural-variant frontotemporal dementia and suggest a feedback-style network, including anterior and posterior brain regions, is involved in early face processing.



http://ift.tt/2CLuz3N

When embodiment breaks down: Language deficits as novel avenues into movement disorders

Publication date: March 2018
Source:Cortex, Volume 100
Author(s): Adolfo M. García, Agustín Ibáñez




http://ift.tt/2oxmThe

“Probing the role of the vestibular system in motivation and reward-based attention”

Publication date: Available online 27 February 2018
Source:Cortex
Author(s): Elvio Blini, Caroline Tilikete, Alessandro Farnè, Fadila Hadj-Bouziane
The vestibular system has widespread connections in the central nervous system. Several activation loci following vestibular stimulations have been notably reported in deep, limbic areas that are otherwise difficult to reach and modulate in healthy subjects. Following preliminary evidence, suggesting that such stimulations might affect mood and affective processing, we wondered whether the vestibular system is also involved in motivation. Evolutionary accounts suggest that visuo-vestibular mismatches might have a role in preventing the search for and exploitation of goods that previously resulted in aversive reactions, as they would be a fine warning signal which follows the contact with or ingestion of noxious neurotoxins. The first question was thus whether vestibular stimulation alters sensitivity to reward. Secondly, we sought to assess whether attention is allocated in space differently when cued by highly motivational stimuli, and if this interplay is further modulated by the vestibular system. In order to evaluate both motivational and attentional assets, we administered a Posner-like cueing task to 30 healthy subjects concurrently receiving sham or Galvanic Vestibular Stimulation (GVS; Left-Anodal and Right-Anodal configurations). The participants had to discriminate targets appearing in either exogenously cued or uncued locations (50% validity); cues predicted the amount of points (0, 2, or 10) and thus money that they could earn for a correct response. The results highlight a robust inhibition of return (faster responses for invalidly-cued targets) which was not modulated by different levels of reward or GVS. Across all stimulation sessions, rewards exerted a powerful beneficial effect over performance: reaction times were faster when rewards were at stake. However, this effect was largest in sham, but greatly reduced in GVS conditions, most notably with the Right-Anodal configuration. This is the first evidence for a decreased sensitivity to rewards causally induced by a perturbation of the vestibular system. While future studies will shed light on its neural underpinnings and clinical implications, here we argue that GVS could be a safe and promising way to enrich our understanding of reward processes and eventually tackle the management of patients with aberrant sensitivity to rewards.



http://ift.tt/2CLEoio

Appropriate timing for postimplant imaging in permanent breast seed implant: Results from a serial CT study

Publication date: Available online 26 February 2018
Source:Brachytherapy
Author(s): Elizabeth Watt, Leigh Conroy, Michael Peacock, Michael Roumeliotis, Amy Frederick, Siraj Husain, Tyler Meyer
PurposePostimplant analysis in permanent breast seed implant (PBSI) is performed at inconsistent times subsequent to seed implantation across cancer centers, creating challenges in the interpretation of dosimetric data and ultimately the correlation with clinical outcomes. The purpose of this study is to determine the most appropriate time postimplant to perform this analysis.Methods and MaterialsNine patients treated at our institution with PBSI were included in this analysis. Each underwent 4 postimplant CT scans: 0, 15, 30, and 60 days postimplant. A model of the accumulated dose was created by deformably registering the Day 15, 30, and 60 postimplant CT scans and dose matrices to the Day 0 scan, scaling for seed decay. The results from this model were compared to each individual postplan by integral comparison of dose–volume histogram curves for a dose evaluation volume.ResultsThe Day 30 postplan showed the best agreement with the accumulated dose model and the smallest interpatient variability across the patient cohort. The mean (±SD) for the dose evaluation volume V90, V100, V150, and V200 for the accumulated dose model was 90 ± 7%, 86 ± 8%, 66 ± 14%, and 41 ± 16%, respectively.ConclusionsBased on the results of this patient cohort, we recommend that postimplant dosimetric analysis for PBSI be performed approximately 30 days following the implant.



http://ift.tt/2otRPiA