RIPK3/MLKL-Mediated Neuronal Necroptosis Modulates the M1/M2 Polarization of Microglia/Macrophages in the Ischemic Cortex

Abstract

Cell death and subsequent inflammation are 2 key pathological changes occurring in cerebral ischemia. Active microglia/macrophages play a double-edged role depending on the balance of their M1/M2 phenotypes. Necrosis is the predominant type of cell death following ischemia. However, how necrotic cells modulate the M1/M2 polarization of microglia/macrophages remains poorly investigated. Here, we reported that ischemia induces a rapid RIPK3/MLKL-mediated neuron-dominated necroptosis, a type of programmed necrosis. Ablating RIPK3 or MLKL could switch the activation of microglia/macrophages from M1 to the M2 type in the ischemic cortex. Conditioned medium of oxygen-glucose deprivation (OGD)-treated wild-type (WT) neurons induced M1 polarization, while that of RIPK3^−/− neurons favored M2 polarization. OGD treatment induces proinflammatory IL-18 and TNFα in WT but not in RIPK3^−/− neurons, which in turn upregulate anti-inflammatory IL-4 and IL-10. Furthermore, the expression of Myd88—a common downstream adaptor of toll-like receptors—is significantly upregulated in the microglia/macrophages of ischemic WT but not of RIPK3^−/− or MLKL^−/− cortices. Antagonizing the function of Myd88 could phenocopy the effects of RIPK3/MLKL-knockout on the polarization of microglia/macrophages and was neuroprotective. Our data revealed a novel role of necroptotic neurons in modulating the M1/M2 balance of microglia/macrophages in the ischemic cortex, possibly through Myd88 signaling.

https://ift.tt/2I7Hcd8

Adult Human Hippocampus: No New Neurons in Sight

Abstract

In this issue of Cerebral Cortex, Cipriani et al. are following up on the recent report of Sorrels et al. to add novel immunohistological observations indicating that, unlike rodents, adult and aging humans do not acquire new neurons in the hippocampus. The common finding emerging from these 2 different, but almost simultaneous studies is highly significant because the dentate gyrus of the hippocampus was, until recently, considered as the only structure in the human brain that may continue neurogenesis throughout the full life span.

https://ift.tt/2ruEDvv

Adjusting oral oxybutynin medication for hyperhidrosis to reflect seasonal temperature variations

Dermatologic Therapy, EarlyView.


https://ift.tt/2jKcvzY

Predicted sequence of cortical tau and amyloid-β deposition in Alzheimer disease spectrum

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Hanna Cho, Hye Sun Lee, Jae Yong Choi, Jae Hoon Lee, Young Hoon Ryu, Myung Sik Lee, Chul Hyoung Lyoo
We investigated sequential order between tau and amyloid-β (Aβ) deposition in Alzheimer disease spectrum using a conditional probability method. Two hundred twenty participants underwent ¹⁸F-flortaucipir and ¹⁸F-florbetaben positron emission tomography scans and neuropsychological tests. The presence of tau and Aβ in each region and impairment in each cognitive domain were determined by Z-score cutoffs. By comparing pairs of conditional probabilities, the sequential order of tau and Aβ deposition were determined. Probability for the presence of tau in the entorhinal cortex was higher than that of Aβ in all cortical regions, and in the medial temporal cortices, probability for the presence of tau was higher than that of Aβ. Conversely, in the remaining neocortex above the inferior temporal cortex, probability for the presence of Aβ was always higher than that of tau. Tau pathology in the entorhinal cortex may appear earlier than neocortical Aβ and may spread in the absence of Aβ within the neighboring medial temporal regions. However, Aβ may be required for massive tau deposition in the distant cortical areas.



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Perfusion alterations converge with patterns of pathological spread in transactive response DNA-binding protein 43 proteinopathies

Publication date: August 2018
Source:Neurobiology of Aging, Volume 68
Author(s): Pilar M. Ferraro, Charles Jester, Christopher A. Olm, Katerina Placek, Federica Agosta, Lauren Elman, Leo McCluskey, David J. Irwin, John A. Detre, Massimo Filippi, Murray Grossman, Corey T. McMillan
Amyotrophic lateral sclerosis (ALS) and the behavioral variant of frontotemporal dementia (bvFTD) commonly share the presence of transactive response DNA-binding protein 43 (TDP-43) inclusions. Structural magnetic resonance imaging studies demonstrated evidence for TDP-43 pathology spread, but while structural imaging usually reveals overt neuronal loss, perfusion imaging may detect more subtle neural activity alterations. We evaluated perfusion as an early marker for incipient pathology–associated brain alterations in TDP-43 proteinopathies. Cortical thickness (CT) and perfusion measurements were obtained in ALS (N = 18), pathologically and/or genetically confirmed bvFTD-TDP (N = 12), and healthy controls (N = 33). bvFTD showed reduced frontotemporal CT, hypoperfusion encompassing orbitofrontal and temporal cortices, and hyperperfusion in motor and occipital regions. ALS did not show reduced CT, but exhibited hypoperfusion in motor and temporal regions, and hyperperfusion in frontal and occipital cortices. Frontotemporal hypoperfusion and reduced CT correlated with cognitive and behavioral impairments as investigated using Mini-Mental State Examination and Philadelphia Brief Assessment of Cognition in bvFTD, and hypoperfusion in motor regions correlated with motor disability as measured by the ALS Functional Rating Scale-Revised in ALS. Hypoperfusion marked early pathologically involved regions, while hyperperfusion characterized regions of late pathological involvement. Distinct perfusion patterns may provide early markers of pathology distribution in TDP-43 proteinopathies.



https://ift.tt/2FYKiOA

Bactericide effect of methylene blue associated with low-level laser therapy in Escherichia coli bacteria isolated from pressure ulcers

Abstract

The present study analyzed the bactericidal effect of methylene blue associated with low-level lasers on Escherichia coli isolated from a pressure ulcer. Microbiological material from a pressure ulcer was isolated using an aseptic swab, and antimicrobial activity was verified using the diffusion disc method. Methylene blue was used at concentrations of 0.001 and 0.005%, and low-level lasers of 670, 830, and 904 nm, with the energy densities of 4, 8, 10, and 14 J/cm², were tested on three plates each and combined with methylene blue of each concentration. In addition, three control plates were used, with each concentration and energy density separated without any interventions. The results were analyzed using the paired sample t test to determine the bactericidal effect of the methylene blue and using the ANOVA test to compare the effects of the energy densities and wavelengths among the low-level laser treatment protocols. The results showed bacterial reduction at wavelengths of 830 and 904 nm and more proliferation in wavelengths of 670 nm. In wavelength of 830 nm, a bacterial reduction was observed in the conditions with 0.001% methylene blue in all energy density utilized, with 0.005% methylene blue in energy density of 10 J/cm², and without methylene blue in energy density at 10 J/cm². And in a wavelength of 904 nm, all condition showed bacterial reduction with or without methylene blue. We concluded that the low-level lasers of 904 and 830 nm have bactericidal effects and at better energy densities (10 and 14 J/cm²).

https://ift.tt/2rwHVyb

The role of nicotinic receptor genes (CHRN) in the pathways of prenatal tobacco exposure on smoking behavior among young adult light smokers

Publication date: September 2018
Source:Addictive Behaviors, Volume 84
Author(s): Arielle S. Selya, Dale S. Cannon, Robert B. Weiss, Lauren S. Wakschlag, Jennifer S. Rose, Lisa Dierker, Donald Hedeker, Robin J. Mermelstein
BackgroundPrenatal tobacco exposure (PTE) is associated with more frequent smoking among young, light smokers. Little is known about how nicotinic acetylcholine receptor (CHRN) genes may contribute to this relationship.MethodsData were drawn from a longitudinal cohort of young light smokers of European ancestry (N = 511). Three single nucleotide polymorphisms (SNPs) among offspring, rs16969968 and rs6495308 in CHRNA5A3B4 and rs2304297 in CHRNB3A6, were analyzed with respect to whether they 1) predict PTE status; 2) confound the previously-reported effects of PTE on future smoking; 3) have effects on youth smoking frequency that are mediated through PTE; and 4) have effects that are moderated by PTE.Resultsrs2304297 and rs6495308 were associated with increased likelihood and severity of PTE, respectively. In a path analysis, rs16969968 directly predicted more frequent smoking in young adulthood (B = 1.50, p = .044); this association was independent of, and not mediated by, PTE. The risk of rs16969968 (IRR = 1.07, p = .015) and the protective effect of rs2304297 (IRR = 0.84, p < .001) on smoking frequency were not moderated by PTE. PTE moderated the effect of rs6495308, such that these alleles were protective against later smoking frequency only among non-exposed youth (IRR = 0.85, p < .001).ConclusionsThe association between offspring CHRNB3A6 and PTE is a novel finding. The risk of rs16969968 on youth smoking is independent and unrelated to that of PTE among young, light smokers. PTE moderates the protective effect of rs6495308 on youth smoking frequency. However, PTE's pathway to youth smoking behavior was not explained by these genetic factors, leaving its mechanism(s) of action unclear.



https://ift.tt/2IlVVob

Estrogens and selective estrogen receptor modulators differentially antagonize Runx2 in ST2 mesenchymal progenitor cells

Publication date: Available online 8 May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Yonatan Amzaleg, Jie Ji, Donlaporn Kittivanichkul, Anna E Törnqvist, Sara Windahl, Elias Sabag, Aysha B. Khalid, Hal Sternberg, Michael West, John A. Katzenellenbogen, Susan A. Krum, Nyam-Osor Chimge, Dustin E. Schones, Yankel Gabet, Claes Ohlsson, Baruch Frenkel
Estrogens attenuate bone turnover by inhibiting both osteoclasts and osteoblasts, in part through antagonizing Runx2. Apparently conflicting, stimulatory effects in osteoblast lineage cells, however, sway the balance between bone resorption and bone formation in favor of the latter. Consistent with this dualism, 17ß-estradiol (E2) both stimulates and inhibits Runx2 in a locus-specific manner, and here we provide evidence for such locus-specific regulation of Runx2 by E2 in vivo. We also demonstrate dual, negative and positive, regulation of Runx2-driven alkaline phosphatase (ALP) activity by increasing E2 concentrations in ST2 osteoblast progenitor cells. We further compared the effects of E2 to those of the Selective Estrogen Receptor Modulators (SERMs) raloxifene (ral) and lasofoxifene (las) and the phytoestrogen puerarin. We found that E2 at the physiological concentrations of 0.1-1 nM, as well as ral and las, but not puerarin, antagonize Runx2-driven ALP activity. At ≥10 nM, E2 and puerarin, but not ral or las, stimulate ALP relative to the activity measured at 0.1-1 nM. Contrasting the difference between E2 and SERMs in ST2 cells, they all shared a similar dose-response profile when inhibiting pre-osteoclast proliferation. That ral and las poorly mimic the locus- and concentration-dependent effects of E2 in mesenchymal progenitor cells may help explain their limited clinical efficacy.

Graphical abstract

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Basal glucocorticoid receptor activation induces proliferation and inhibits neuronal differentiation of human induced pluripotent stem cell-derived neuronal precursor cells

Publication date: Available online 8 May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Elina Nürnberg, Sandra Horschitz, Patrick Schloss, Andreas Meyer-Lindenberg
Glucocorticoids (GC) have first been shown to originate from the adrenal glands where synthesis and release is controlled by the hypothalamic-pituitary-adrenal (HPA) axis. Recently, it was shown that GC and other steroid hormones are also synthesized in the central nervous system, so-called neurosteroids. GC bind to specific GC receptors (GR) which function as ligand-activated transcription factors. GR are expressed in nearly all cell types in the brain, and therefore GC have a strong impact on neuronal development.Most knowledge of the influence of GC on neurodevelopment has been obtained from animal research. Recent advances in stem cell technology made it possible to generate neuronal precursor cells (NPCs) and neurons from human induced pluripotent stem cells (hiPSCs). To explore the cellular mechanism of GC affecting human neuronal development, we quantified the proliferation and differentiation of hiPSCs–derived NPCs in the absence and presence of the selective high-affinity GR agonist dexamethasone and the selective GR antagonist mifepristone, respectively. Our results show that inhibition of GR significantly reduced proliferation of NPCs and promoted differentiation whereas GR activation suppressed neuronal differentiation. This implies that neuronal GC must be present in NPCs for proliferation. Consequently we identified the presence of 11-β-hydroxylase CYP11B1, which hydroxylates the respective steroid precursors to bioactive GC, in NPCs.We propose that hiPSC technology offers an ideal system to get more insight into the synthesising and regulatory pathways in steroidogenesis in human neurons and to differentiate between the mechanism by which adrenal GC and neuronal GC impact on neurodevelopment.

Graphical abstract

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Update on Tumor Neoantigens and Their Utility: Why It Is Good to Be Different

Publication date: Available online 8 May 2018
Source:Trends in Immunology
Author(s): Chung-Han Lee, Roman Yelensky, Karin Jooss, Timothy A. Chan
Antitumor rejection by the immune system is a complex process that is regulated by several factors. Among these factors are the quality and quantity of mutational events that occur in cancer cells. Perhaps one of the most important types of mutations that influence antitumor immunity is the neoantigen, that is, a non-self-antigen that arises as a result of somatic mutation. Recent work has demonstrated that neoantigens hold significant promise for developing new diagnostic and therapeutic modalities. Therapeutic targeting of neoantigens is important for achieving benefit following therapy with immune checkpoint blockade agents or for cancer vaccines targeting mutations. Here, we review our understanding of neoantigens and discuss new developments in the quest to use them in cancer immunotherapy.



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Curcumin derived Schiff base ligand and their transition metal complexes: Synthesis, spectral characterization, catalytic potential and biological activity

Publication date: 5 September 2018
Source:Journal of Molecular Structure, Volume 1167
Author(s): Abdul Kareem, Mohd Shoeb Khan, Shahab A.A. Nami, Shahnawaz A. Bhat, Azar Ullah Mirza, Nahid Nishat
Curcumin derived Schiff base ligand, (CL), was prepared by condensation of 1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin) with amino ethylene piperazine (AEP). The transition metal complexes of CL were also successfully synthesized and characterized by various spectroscopic techniques. Non-electrolytic nature of complexes was ascertained by molar conductance values. Thermogravimetric analysis confirms that all the metal complexes are stable up to 600 °C. The metal to ligand stoichiometry of synthesized metal complexes was confirmed by micro analytical data as 1:1 (metal: ligand). Co(II), Ni(II) and Zn(II) ion forms the complexes with an octahedral geometry while the geometry of Cu(II) complex can ascribed as square planar by UV–vis and EPR spectroscopic studies. Catalytic power and antioxidant activity of these complexes have been evaluated and results shows that Co(II) complex is catalytically more active while the Cu(II) and Zn(II) complex were found with more potent antioxidant activity, comparatively. The synthesized compounds have also been tested for their in-vitro cytotoxic potential, the obtained results shows moderate to good cytotoxicity on tested human cancer cell lines. The most effective compounds on cell lines MDA-MB-231 and KCL22 was [(CL)Cu] while on HeLa cell line the [(CL)Zn(H2O)2] was found with prominent cytotoxicity. Anthelmintic activities of these compounds have been performed using Pheretima posthuma. The recorded order of anthelmintic activity of ligand (CL) and their metal complexes was found to have the trend as: [(CL)Cu]>[(CL)Zn(H2O)2]>[(CL)Co(H2O)2]>[(CL)Ni(H2O)2]>CL.

Graphical abstract

https://ift.tt/2FY8Ozo

Fractionation and mobility risks of heavy metals and metalloids in wastewater-irrigated agricultural soils from greenhouses and fields in Gansu, China

Publication date: 15 October 2018
Source:Geoderma, Volume 328
Author(s): Chun Cao, Qiang Zhang, Zhen-Bang Ma, Xue-Mei Wang, Huan Chen, Jun-Jian Wang
Wastewater irrigation reduces the pressure on freshwater usage but leads to the accumulation of heavy metal(loid)s in soils. This study investigated heavy metal(loid)s (As, Cr, Cu, Ni, Pb, and Zn) in the acid-soluble (F1), reducible (F2), oxidizable (F3), and residual (F4) fractions of soils from greenhouses and fields in Baiyin City, Gansu, China, which had been irrigated with treated industrial and municipal wastewater. Risk assessment (RAC) and modified risk assessment (mRAC) codes were used to estimate the environmental risks based on metal mobility. Results showed that more than half of each studied heavy metal(loid) (72.6%–97.4%) was present in the residual fraction (F4), which is non-bioavailable. Both the concentrations and percentages of metals in the bio-accessible fractions (F1, F2, and F3) showed no significant differences (p > 0.05) between rhizosphere and bulk soils. The greenhouse soils had higher concentrations and percentages of metals (except Pb) in bio-accessible fractions compared with field soils. Similarly, compared with irrigation using treated municipal wastewater, irrigation with treated industrial wastewater resulted in higher concentrations and percentages of all the studied metals in the bio-accessible fractions of soils. The average RAC value of each heavy metal(loid) in soils suggested medium risks from Zn, low risks from As, Cu, Ni, and Pb, and no risks from Cr. According to the mRAC values for 120 soil samples, there were only 13.3% of soils with no potential adverse effect, but 83.3% of soils with a low potential adverse effect and 3.3% of soils with a medium potential adverse effect.



https://ift.tt/2KOP310

Responses of microbial tolerance to heavy metals along a century-old metal ore pollution gradient in a subarctic birch forest

Publication date: September 2018
Source:Environmental Pollution, Volume 240
Author(s): Johannes Rousk, Kathrin Rousk
Heavy metals are some of the most persistent and potent anthropogenic environmental contaminants. Although heavy metals may compromise microbial communities and soil fertility, it is challenging to causally link microbial responses to heavy metals due to various confounding factors, including correlated soil physicochemistry or nutrient availability. A solution is to investigate whether tolerance to the pollutant has been induced, called Pollution Induced Community Tolerance (PICT). In this study, we investigated soil microbial responses to a century-old gradient of metal ore pollution in an otherwise pristine subarctic birch forest generated by a railway source of iron ore transportation. To do this, we determined microbial biomass, growth, and respiration rates, and bacterial tolerance to Zn and Cu in replicated distance transects (1 m–4 km) perpendicular to the railway. Microbial biomass, growth and respiration rates were stable across the pollution gradient. The microbial community structure could be distinguished between sampled distances, but most of the variation was explained by soil pH differences, and it did not align with distance from the railroad pollution source. Bacterial tolerance to Zn and Cu started from background levels at 4 km distance from the pollution source, and remained at background levels for Cu throughout the gradient. Yet, bacterial tolerance to Zn increased 10-fold 100 m from the railway source. Our results show that the microbial community structure, size and performance remained unaffected by the metal ore exposure, suggesting no impact on ecosystem functioning.

Graphical abstract

Teaser

An induced bacterial Zn-tolerance demonstrated that pristine soil microbial communities had been contaminated by metal pollution derived from iron ore transport.


https://ift.tt/2FWX4NK

Synthesis of highly stable CuInZnS/ZnS//ZnS quantum dots with thick shell and its application to quantitative immunoassay

Publication date: 15 September 2018
Source:Chemical Engineering Journal, Volume 348
Author(s): Ruili Wu, Tianyue Wang, Min Wu, Yanbing Lv, Xueping Liu, Jinjie Li, Huaibin Shen, Lin Song Li
In this paper, CuInZnxS2+x (CIZS, x = 1) have been used as cadmium-free core materials to synthesize CIZS-based core/shell quantum dots (QDs). By introducing extra Zn precursor to CIZS cores, two-time separate shell growth process, and continuous long time replenishment of shell precursor, cation exchange between Cu and Zn ions during the growth of the ZnS shell has been greatly reduced and as large as 7.8 ± 1.2 nm CIZS/ZnS//ZnS with an average of 3.1 nm shell were synthesized successfully. Such thick shell CIZS/ZnS//ZnS core/shell QDs had high stability and high quantum yields (77%). Compared with the thin shell CIZS/ZnS QDs, the thick shell CIZS/ZnS//ZnS QDs still showed excellent PLQY (up to 58%) and stability in different environment after transfer to aqueous solution. We adopted the thick shell cadmium-free QDs as fluorescence label into lateral flow immunoassay for quantitative detection of C-reactive protein, and the limit of detection was 5.8 ng/mL, which was almost as low as that of cadmium-based quantum dot lateral flow test strip. Therefore, this kind of thick shell CIZS/ZnS//ZnS QDs can be used as probes for ultra-sensitive detection, and the further development of this kind of QDs has immense potential for future convenient and cost-effective in vitro cadmium-free nano-medical diagnostic kits.

Graphical abstract

https://ift.tt/2jIaq7D

Syntheses, crystal structures and photophysical properties of a series of Zn-Ln coordination polymers

Publication date: 5 September 2018
Source:Journal of Molecular Structure, Volume 1167
Author(s): Shu Hou, Xiao-Yun Tang, Yue Li, Rui-Xue Wang, Fei-Fei Chen, Yan Wang, Yu-Xian Chi, Jing Jin
A series of coordination polymers, {[LnZn(2,3-pydc)(1,3-bdc)(OH)(H2O)m]·H2O}n, (Ln = Sm 1, Eu 2, Gd 3, Tb 4, Dy 5, Er 6, Yb 7, Pr 8, Nd 9), (1–7, m = 1; 8, 9, m = 2), (2,3-H2pydc = pyridine-2,3-dicarboxylic acid, 1,3-H2bdc = isophthalic acid), are synthesized by the hydrothermal method and their crystal structures are determined by single-crystal X-ray diffraction. Structural analysis shows that coordination polymers 1–9 present two-dimensional layered structures and all of them are crystalized in triclinic system with space group Pī. Hereinto polymers 1–7 are isomorphous, while polymers 8 and 9 are also isomorphous and each of them includes one more coordinated water molecule than others. All coordination polymers are characterized by IR, UV–Vis–NIR and fluorescent spectra, and the luminescent properties are the research emphasis. In addition, except for polymer 3, the other eight Zn-Ln polymers exhibit the characteristic luminescence of corresponding Ln(III) ions, which should be owing to the sensitization of the Zn-Ligand moiety. With the influence of the crystal field and the introduction of Zn(II) ion, the internal energy levels of the system are tuned, which is reflected by shift and split of the partial characteristic bands of Ln(III) ions in their UV–Vis–NIR absorption spectra and NIR emission spectra, and both can corroborate each other.

Graphical abstract

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Phosphorylation Leads the Way for Protein Aggregate Disassembly

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Steven Boeynaems, Aaron D. Gitler
Protein aggregation can be beneficial, with important biological functions, but must be somehow controlled. In this issue of Developmental Cell, Carpenter et al. (2018) uncover how a solid-like supermolecular protein assembly that regulates yeast meiosis is disassembled through phosphorylation of a disordered prion-like domain to control the timing of meiotic progression.

Teaser

Protein aggregation can be beneficial, with important biological functions, but must be somehow controlled. In this issue of Developmental Cell, Carpenter et al. (2018) uncover how a solid-like supermolecular protein assembly that regulates yeast meiosis is disassembled through phosphorylation of a disordered prion-like domain to control the timing of meiotic progression.


https://ift.tt/2wo13TM

Tuning Division and Differentiation in Stomata: How to Silence a MUTE

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Jorge Zamora-Zaragoza, Ben Scheres
Precise coordination of cell differentiation and division within a tissue context is critical for plant development. In this issue of Developmental Cell, Han et al. (2018) report a transcriptional switch that ensures proper patterning, the final cell division, and terminal differentiation of stomata.

Teaser

Precise coordination of cell differentiation and division within a tissue context is critical for plant development. In this issue of Developmental Cell, Han et al. (2018) report a transcriptional switch that ensures proper patterning, the final cell division, and terminal differentiation of stomata.


https://ift.tt/2I01KYY

Synaptotagmins Tweak Functional β Cell Maturation

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Jennifer M. Gilbert, Barak Blum
Immature β cells secrete insulin at a lower glucose threshold compared to mature β cells. In this issue of Developmental Cell, Huang et al. (2018) show that the increase in glucose threshold during β cell maturation is achieved through balance between the Ca²⁺-sensitive synaptotagmin 7 and the Ca²⁺-insensitive synaptotagmin 4.

Teaser

Immature β cells secrete insulin at a lower glucose threshold compared to mature β cells. In this issue of Developmental Cell, Huang et al. (2018) show that the increase in glucose threshold during β cell maturation is achieved through balance between the Ca²⁺-sensitive synaptotagmin 7 and the Ca²⁺-insensitive synaptotagmin 4.


https://ift.tt/2I83kUP

Structural Centrosomal Abnormalities Push Cells toward Invasion

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Pedro Monteiro, Susana A. Godinho
Structural centrosomal aberrations have long been described in cancer, but their impact on cell physiology and tumorigenesis remains unclear. Ganier et al. (2018) show that centrosome structural abnormalities facilitate cell dissemination by promoting budding of epithelial mitotic cells.

Teaser

Structural centrosomal aberrations have long been described in cancer, but their impact on cell physiology and tumorigenesis remains unclear. Ganier et al. (2018) show that centrosome structural abnormalities facilitate cell dissemination by promoting budding of epithelial mitotic cells.


https://ift.tt/2rtsvKT

Emerging Concepts in Organ-Specific Lymphatic Vessels and Metabolic Regulation of Lymphatic Development

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Brian W. Wong, Annalisa Zecchin, Melissa García-Caballero, Peter Carmeliet
The lymphatic system has been less well characterized than the blood vascular system; however, work in recent years has uncovered novel regulators and non-venous lineages that contribute to lymphatic formation in various organs. Further, the identification of organ-specific lymphatic beds underscores their potential interaction with organ development and function, and highlights the possibility of targeting these organ-specific lymphatics beds in disease. This review focuses on newly described metabolic and epigenetic regulators of lymphangiogenesis and the interplay between lymphatic development and function in a number of major organ systems.

Teaser

Wong et al. present a Review focusing on two emerging aspects of lymphatic development. They discuss both metabolic and epigenetic regulators of lymphangiogenesis as well as the interplay between lymphatic development and function in several organ systems.


https://ift.tt/2I3YQOL

The Power of Strain: Organizing Left-Right Cilia

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Martin Blum, Tim Ott
Left-right organizers require motile and polarized cilia to break symmetry. In this issue of Developmental Cell, Chien et al. (2018) demonstrate that gastrulation-derived mechanical strain of the precursor tissue orients cilia and is required for cilia lengthening and motility.

Teaser

Left-right organizers require motile and polarized cilia to break symmetry. In this issue of Developmental Cell, Chien et al. (2018) demonstrate that gastrulation-derived mechanical strain of the precursor tissue orients cilia and is required for cilia lengthening and motility.


https://ift.tt/2rtKRLP

MUTE Directly Orchestrates Cell-State Switch and the Single Symmetric Division to Create Stomata

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Soon-Ki Han, Xingyun Qi, Kei Sugihara, Jonathan H. Dang, Takaho A. Endo, Kristen L. Miller, Eun-Deok Kim, Takashi Miura, Keiko U. Torii
Precise cell division control is critical for developmental patterning. For the differentiation of a functional stoma, a cellular valve for efficient gas exchange, the single symmetric division of an immediate precursor is absolutely essential. Yet, the mechanism governing this event remains unclear. Here we report comprehensive inventories of gene expression by the Arabidopsis bHLH protein MUTE, a potent inducer of stomatal differentiation. MUTE switches the gene expression program initiated by SPEECHLESS. MUTE directly induces a suite of cell-cycle genes, including CYCD5;1, in which introduced expression triggers the symmetric divisions of arrested precursor cells in mute, and their transcriptional repressors, FAMA and FOUR LIPS. The regulatory network initiated by MUTE represents an incoherent type 1 feed-forward loop. Our mathematical modeling and experimental perturbations support a notion that MUTE orchestrates a transcriptional cascade leading to a tightly restricted pulse of cell-cycle gene expression, thereby ensuring the single cell division to create functional stomata.

Graphical abstract

Teaser

Stomata, small valves on the plant epidermis, are made of two guard cells surrounding a pore. Han et al. show that the transcription factor MUTE orchestrates gene regulatory circuits to switch cells to a differentiation state, then ensures that only a single symmetric division occurs to create a functional stoma.


https://ift.tt/2I77KLB

Mechanical Strain Determines Cilia Length, Motility, and Planar Position in the Left-Right Organizer

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Yuan-Hung Chien, Shyam Srinivasan, Ray Keller, Chris Kintner
The Xenopus left-right organizer (LRO) breaks symmetry along the left-right axis of the early embryo by producing and sensing directed ciliary flow as a patterning cue. To carry out this process, the LRO contains different ciliated cell types that vary in cilia length, whether they are motile or sensory, and how they position their cilia along the anterior-posterior (A-P) planar axis. Here, we show that these different cilia features are specified in the prospective LRO during gastrulation, based on anisotropic mechanical strain that is oriented along the A-P axis, and graded in levels along the medial-lateral axis. Strain instructs ciliated cell differentiation by acting on a mesodermal prepattern present at blastula stages, involving foxj1. We propose that differential strain is a graded, developmental cue, linking the establishment of an A-P planar axis to cilia length, motility, and planar location during formation of the Xenopus LRO.

Graphical abstract

Teaser

The left-right body axis is established in Xenopus embryos by leftward fluid flow produced and sensed in the left-right organizer. Chien et al. show that the pattern of cilia differentiation required to produce this flow is determined by graded and oriented mechanical strain during gastrulation.


https://ift.tt/2jJZRBa

Drosophila TNF Modulates Tissue Tension in the Embryo to Facilitate Macrophage Invasive Migration

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Aparna Ratheesh, Julia Biebl, Jana Vesela, Michael Smutny, Ekaterina Papusheva, S.F. Gabriel Krens, Walter Kaufmann, Attila Gyoergy, Alessandra Maria Casano, Daria E. Siekhaus
Migrating cells penetrate tissue barriers during development, inflammatory responses, and tumor metastasis. We study if migration in vivo in such three-dimensionally confined environments requires changes in the mechanical properties of the surrounding cells using embryonic Drosophila melanogaster hemocytes, also called macrophages, as a model. We find that macrophage invasion into the germband through transient separation of the apposing ectoderm and mesoderm requires cell deformations and reductions in apical tension in the ectoderm. Interestingly, the genetic pathway governing these mechanical shifts acts downstream of the only known tumor necrosis factor superfamily member in Drosophila, Eiger, and its receptor, Grindelwald. Eiger-Grindelwald signaling reduces levels of active Myosin in the germband ectodermal cortex through the localization of a Crumbs complex component, Patj (Pals-1-associated tight junction protein). We therefore elucidate a distinct molecular pathway that controls tissue tension and demonstrate the importance of such regulation for invasive migration in vivo.

Teaser

It is important to understand how the mechanical properties of surrounding tissues influence immune cells' progress during their in vivo migration. Here, Ratheesh et al. show that Drosophila TNF facilitates macrophage invasion by lowering active Myosin levels and thus apical tension in the ectoderm through enhanced localization of Patj.


https://ift.tt/2I7KmgW

A Dendritic Guidance Receptor Complex Brings Together Distinct Actin Regulators to Drive Efficient F-Actin Assembly and Branching

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Wei Zou, Xintong Dong, Timothy R. Broederdorf, Ao Shen, Daniel A. Kramer, Rebecca Shi, Xing Liang, David M. Miller, Yang K. Xiang, Ryohei Yasuda, Baoyu Chen, Kang Shen
Proper morphogenesis of dendrites plays a fundamental role in the establishment of neural circuits. The molecular mechanism by which dendrites grow highly complex branches is not well understood. Here, using the Caenorhabditis elegans PVD neuron, we demonstrate that high-order dendritic branching requires actin polymerization driven by coordinated interactions between two membrane proteins, DMA-1 and HPO-30, with their cytoplasmic interactors, the RacGEF TIAM-1 and the actin nucleation promotion factor WAVE regulatory complex (WRC). The dendrite branching receptor DMA-1 directly binds to the PDZ domain of TIAM-1, while the claudin-like protein HPO-30 directly interacts with the WRC. On dendrites, DMA-1 and HPO-30 form a receptor-associated signaling complex to bring TIAM-1 and the WRC to close proximity, leading to elevated assembly of F-actin needed to drive high-order dendrite branching. The synergistic activation of F-actin assembly by scaffolding distinct actin regulators might represent a general mechanism in promoting complex dendrite arborization.

Graphical abstract

Teaser

Zou et al. uncover a molecular mechanism for complex dendrite formation. The dendrite guidance receptor DMA-1 interacts with the claudin-like protein HPO-30 to scaffold two actin regulators, the RacGEF TIAM-1 and the WAVE regulatory complex. The spatial proximity of these factors promotes efficient actin polymerization and drives high-order dendritic branching.


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Atypical Cadherin Dachsous1b Interacts with Ttc28 and Aurora B to Control Microtubule Dynamics in Embryonic Cleavages

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Jiakun Chen, Gina D. Castelvecchi, Nanbing Li-Villarreal, Brian Raught, Andrzej M. Krezel, Helen McNeill, Lilianna Solnica-Krezel
Atypical cadherin Dachsous (Dchs) is a conserved regulator of planar cell polarity, morphogenesis, and tissue growth during animal development. Dchs functions in part by regulating microtubules by unknown molecular mechanisms. Here we show that maternal zygotic (MZ) dchs1b zebrafish mutants exhibit cleavage furrow progression defects and impaired midzone microtubule assembly associated with decreased microtubule turnover. Mechanistically, Dchs1b interacts via a conserved motif in its intracellular domain with the tetratricopeptide motifs of Ttc28 and regulates its subcellular distribution. Excess Ttc28 impairs cleavages and decreases microtubule turnover, while ttc28 inactivation increases turnover. Moreover, ttc28 deficiency in dchs1b mutants suppresses the microtubule dynamics and midzone microtubule assembly defects. Dchs1b also binds to Aurora B, a known regulator of cleavages and microtubules. Embryonic cleavages in MZdchs1b mutants exhibit increased, and in MZttc28 mutants decreased, sensitivity to Aurora B inhibition. Thus, Dchs1b regulates microtubule dynamics and embryonic cleavages by interacting with Ttc28 and Aurora B.

Teaser

Atypical cadherin Dachsous1b has conserved functions in regulating planar cell polarity and growth in animal development. Chen et al. show that zebrafish Dachsous1b regulates embryonic cleavages and microtubule dynamics through Aurora B and Ttc28. Dachsous1b interacts with Aurora B and Ttc28, via its intracellular domain, and regulates Ttc28 subcellular distribution.


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Phosphorylation-Mediated Clearance of Amyloid-like Assemblies in Meiosis

Publication date: 7 May 2018
Source:Developmental Cell, Volume 45, Issue 3
Author(s): Kayla Carpenter, Rachel Brietta Bell, Julius Yunus, Angelika Amon, Luke Edwin Berchowitz
Amyloids are fibrous protein assemblies that are often described as irreversible and intrinsically pathogenic. However, yeast cells employ amyloid-like assemblies of the RNA-binding protein Rim4 to control translation during meiosis. Here, we show that multi-site phosphorylation of Rim4 is critical for its regulated disassembly and degradation and that failure to clear Rim4 assemblies interferes with meiotic progression. Furthermore, we identify the protein kinase Ime2 to bring about Rim4 clearance via phosphorylation of Rim4's intrinsically disordered region. Rim4 phosphorylation leads to reversal of its amyloid-like properties and degradation by the proteasome. Our data support a model in which a threshold amount of phosphorylation, rather than modification of critical residues, is required for Rim4 clearance. Our results further demonstrate that at least some amyloid-like assemblies are not as irreversible as previously thought. We propose that the natural pathways by which cells process these structures could be deployed to act on disease-related amyloids.

Graphical abstract

Teaser

Amyloids, fibrous protein assemblies associated with numerous diseases, are often referred to as being irreversible structures. Carpenter et al. demonstrate that, in coordination with meiotic development, budding yeast are able to disassemble and clear the amyloid-like translational repressor Rim4 by multi-site phosphorylation of residues within disordered regions of the protein.


https://ift.tt/2jJENuk

Arginine Methylation by PRMT2 Controls the Functions of the Actin Nucleator Cobl

Publication date: 23 April 2018
Source:Developmental Cell, Volume 45, Issue 2
Author(s): Wenya Hou, Sabine Nemitz, Simone Schopper, Michael Lund Nielsen, Michael Manfred Kessels, Britta Qualmann
The complex architecture of neuronal networks in the brain requires tight control of the actin cytoskeleton. The actin nucleator Cobl is critical for neuronal morphogenesis. Here we reveal that Cobl is controlled by arginine methylation. Coprecipitations, coimmunoprecipitations, cellular reconstitutions, and in vitro reconstitutions demonstrated that Cobl associates with the protein arginine methyltransferase PRMT2 in a Src Homology 3 (SH3) domain-dependent manner and that this promotes methylation of Cobl's actin nucleating C-terminal domain. Consistently, PRMT2 phenocopied Cobl functions in both gain- and loss-of-function studies. Both PRMT2- and Cobl-promoted dendritogenesis relied on methylation. PRMT2 effects require both its catalytic domain and SH3 domain. Cobl-mediated dendritic arborization required PRMT2, complex formation with PRMT2, and PRMT2's catalytic activity. Mechanistic studies reveal that Cobl methylation is key for Cobl actin binding. Therefore, arginine methylation is a regulatory mechanism reaching beyond controlling nuclear processes. It also controls a major, cytosolic, cytoskeletal component shaping neuronal cells.

Graphical abstract

Teaser

Hou et al. demonstrate that early morphogenesis of neurons is dependent on arginine methylation. The authors identify the enzyme arginine methyltransferase PRMT2 as key regulator of the actin nucleator Cobl. PRMT2 methylates Cobl and promotes G-actin binding, thereby modulating Cobl's activity in dendritic arborization.


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Cell Identity Switching Regulated by Retinoic Acid Signaling Maintains Homogeneous Segments in the Hindbrain

Publication date: Available online 3 May 2018
Source:Developmental Cell
Author(s): Megan Addison, Qiling Xu, Jordi Cayuso, David G. Wilkinson
The patterning of tissues to form subdivisions with distinct and homogeneous regional identity is potentially disrupted by cell intermingling. Transplantation studies suggest that homogeneous segmental identity in the hindbrain is maintained by identity switching of cells that intermingle into another segment. We show that switching occurs during normal development and is mediated by feedback between segment identity and the retinoic acid degrading enzymes, cyp26b1 and cyp26c1. egr2, which specifies the segmental identity of rhombomeres r3 and r5, underlies the lower expression level of cyp26b1 and cyp26c1 in r3 and r5 compared with r2, r4, and r6. Consequently, r3 or r5 cells that intermingle into adjacent segments encounter cells with higher cyp26b1/c1 expression, which we find is required for downregulation of egr2b expression. Furthermore, egr2b expression is regulated in r2, r4, and r6 by non-autonomous mechanisms that depend upon the number of neighbors that express egr2b. These findings reveal that a community regulation of retinoid signaling maintains homogeneous segmental identity.

Graphical abstract

Teaser

Addison et al. uncover how segments within the hindbrain maintain a homogeneous identity despite intermingling of cells at early stages. Cells that intermingle into an adjacent segment switch identity since they encounter a different level of retinoic acid signaling from their new neighbors.


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How to Make a Billion Parasites

Publication date: 23 April 2018
Source:Developmental Cell, Volume 45, Issue 2
Author(s): Eric S. Haag, Te-Wen Lo
Transmission of the human parasite Brugia malayi relies on the sustained production of larvae in blood. In this issue of Developmental Cell,Foray et al. (2018) use methods developed in the model nematode C. elegans to reveal how a symbiotic bacterium supports the female germ cell development underlying this massive fecundity.

Teaser

Transmission of the human parasite Brugia malayi relies on the sustained production of larvae in blood. In this issue of Developmental Cell, Foray et al. (2018) use methods developed in the model nematode C. elegans to reveal how a symbiotic bacterium supports the female germ cell development underlying this massive fecundity.


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Trifluridine/Tipiracil (TAS‐102) in Refractory Metastatic Colorectal Cancer: A Multicenter Register in the Frame of the Italian Compassionate Use Program

AbstractBackground.TAS‐102 is indicated for patients with metastatic colorectal cancer (mCRC) previously treated with, or not considered candidates for, available therapies. Given the complete inefficacy in half of patients, the lack of predictive factors, the palliative setting, and the financial and clinical toxicity, optimizing the cost‐benefit ratio is crucial. The "ColonLife" nomogram allows an estimate of the 12‐week life expectancy of patients with refractory mCRC.Materials and Methods.We collected data from patients treated at eight Italian centers in the compassionate use program. Baseline characteristics of patients who were or were not progression free at 6 months were compared. The discriminative ability of the ColonLife nomogram was assessed. Among patients who received both TAS‐102 and regorafenib, clinical outcomes of the two sequences were compared.Results.This study included 341 patients. Six (2%) and 93 (27%) patients achieved response and disease stabilization, respectively. The median progression‐free survival (PFS) was 2.4 months with an estimated 6‐month PFS rate of 19%; the median overall survival (OS) was 6.2 months. An Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, normal lactate dehydrogenase (LDH), and a time from the diagnosis of metastatic disease of >18 months were independently associated with higher chances of a patient being progression free at 6 months. The discriminative ability of ColonLife was confirmed. Among 121 patients who received both regorafenib and TAS‐102, no differences in first or second PFS or OS were reported between the two sequences.Conclusion.One out of five patients achieves clinical benefit with TAS‐102. ECOG PS, LDH, and time from diagnosis of metastatic disease may help to identify these patients. Excluding patients with very short life expectancy appears a reasonable approach.Implications for Practice.Improving the cost‐efficacy ratio of TAS‐102 in metastatic colorectal cancer is needed to spare useless toxicities in a definitely palliative setting. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, and time from the diagnosis of metastatic disease may help to identify patients more likely to achieve benefit. Properly designed prognostic tools (i.e., the "ColonLife" nomogram) may enable excluding from further treatments patients with very limited life expectancy.

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Long‐Term Survival Rates of Patients with Stage III–IV Hodgkin Lymphoma According to Age, Sex, Race, and Socioeconomic Status, 1984–2013

AbstractBackground.Long‐term survival rates for patients with stage III–IV Hodgkin lymphoma, or advanced Hodgkin lymphoma (aHL), have increased substantially since the 1960s. Because large‐scale research of aHL is rare, we aimed to demonstrate the differences in incidence and survival of aHL according to four patient variables in recent decades, with a focus on the outcomes of treatment of aHL and the advancement of public health care.Materials and Methods.Data on aHL cases diagnosed during 1984–2013 were extracted from the Surveillance, Epidemiology, and End Results Program database. Relative survival, Kaplan‐Meier, and Cox proportional hazards regression analyses were performed to identify prognosis indicators for aHL.Results.The incidence rates for aHL were 1.1, 0.8, and 1.0 per 100,000 in the first, second, and third decades, respectively, during 1984–2013. The 120‐month relative survival rate improved continuously in each decade from 58.5% to 64.6% to 72.1%. In addition, disparities in the 120‐month relative survival rate between male and female patients and among patients of different races narrowed over time. The difference in long‐term survival rate between the poor (medium and high poverty) and rich (low poverty) groups narrowed across the 3 decades.Conclusion.The long‐term survival rate for patients with aHL increased in each decade, whereas survival rate disparities according to sex, race, and socioeconomic status narrowed, except for older patients aged >60 years and the high‐poverty group.Implications for Practice.Long‐term survival rates of patients with advanced Hodgkin lymphoma were elaborated in this article. The disparities according to sex, race, and socioeconomic status of survival condition were analyzed and showed the development of the public health care system and modern medicine technology.

https://ift.tt/2ruSzFI

EML4‐ALK Rearrangement and Its Therapeutic Implications in Inflammatory Myofibroblastic Tumors

AbstractWith the advent of precision medicine, medical oncology is undergoing a transcendental change. These molecular studies have allowed us to learn about potential targeted therapies for patients with advanced cancers. Perhaps the best‐known example of success in precision medicine is chronic myeloid leukemia and its response to tyrosine kinase inhibitors targeting the BCR‐ABL kinase. Since that original discovery, the role of molecular therapeutics has expanded, and it now presents us with treatment options for common malignancies and rare atypical tumors. In this article, we present a case of a 61‐year‐old female with a recurrent pulmonary inflammatory myofibroblastic tumor. Subsequent molecular studies revealed an ALK rearrangement. The significance of this alteration in this tumor type and its therapeutic implications are discussed herein.Key Points. This case exemplifies the heterogeneous behavior of inflammatory myofibroblastic tumors (IMTs) and the current role of targeted therapy in the therapeutic armamentarium of neoplastic processes.As evidenced by the different mutations found in IMTs, it is of great importance to perform next‐generation sequencing in uncommon neoplasms.These studies can find different potential targets and therapeutic options for patients devoid of standard effective therapies.

https://ift.tt/2K6rfEm

Quantitative Proteomics Analysis of Sporadic Medullary Thyroid Cancer Reveals FN1 as a Potential Novel Candidate Prognostic Biomarker

AbstractBackground.Sporadic medullary thyroid cancer (MTC) is a rare neuroendocrine tumor. Currently, although the diagnosis of sporadic MTC is relatively simple, the need to discover novel candidate prognostic biomarkers for sporadic MTC and investigate the underlying mechanism involved in this rare disease is urgent.Materials and Methods.We employed tandem mass tag‐based liquid chromatography‐mass spectrometry to identify and analyze differentially expressed proteins (DEPs) in sporadic MTC. Western blotting was used to validate the DEPs. Immunohistochemistry was performed to investigate FN1 and RPS6KA3 in an independent set of sporadic MTC tissues. Immunohistochemical data were analyzed by different statistical methods.Results.Three hundred eighty‐eight DEPs were identified in mass spectrometry, mainly involved in the extracellular matrix, cytoskeletal remodeling, or oxidoreductase activity. Among them, THBS1, MMP9, FN1, RPS6KA3, SYT1, and carcinoembryonic antigen were successfully validated by Western blot. In addition, FN1 and RPS6KA3, enriched in extracellular matrix (ECM) remodeling and the mitogen‐activated protein kinase (MAPK) signaling pathway, respectively, were investigated in an independent set of sporadic MTC tissues. Receiver‐operator characteristic curve analysis showed that FN1 and RPS6KA3 can be used for discriminating sporadic MTC tumorous tissues from paired normal thyroid tissues, and the clinical biomarker calcitonin was positively correlated with FN1 and RPS6KA3 in tumorous tissues. Furthermore, the immunohistochemical scores of FN1 in tumorous tissue showed an inverse relationship with tumor classification, lymph node classification, and American Joint Committee on Cancer stage. Through univariate and multivariate analysis for progression‐free survival, we also found that low FN1 expression in tumorous tissues was an independent worse prognostic factor for progression‐free survival.Conclusion.We identified that the pathophysiology of sporadic MTC involve numerous pathways, including the synaptic vesicle pathway, the MAPK signaling pathway, and the ECM remodeling pathway. Furthermore, our study also identified FN1 as novel prognostic biomarkers related to the pathophysiologic changes in sporadic MTC.Implications for Practice.Proteomic dissection and prognostic biomarkers are scarce in sporadic medullary thyroid cancer (MTC). This article reports the use of proteomics technology to comprehensively investigate the molecular mechanisms of sporadic MTC, which resulted in the identification of FN1 as a novel candidate prognostic biomarker.

https://ift.tt/2ruSp14

Cluster Analysis Demonstrates the Need to Individualize Care for Cancer Survivors

AbstractBackground.In efforts to inform clinical screening and development of survivorship care services, we sought to characterize patterns of health care needs among cancer survivors by (a) identifying and characterizing subgroups based on self‐reported health care needs and (b) assessing sociodemographic, clinical, and psychosocial factors associated with these subgroups.Methods.We conducted a cross‐sectional self‐administered survey among patients presenting for routine follow‐up care for early‐stage cancer at our academic medical center. Latent class cluster analysis was used to identify clusters of survivors based on survivorship care needs within seven domains. Multiple logistic regression analyses were used to assess factors associated with these clusters.Results.Among 292 respondents, the highest unmet needs were related to the domains of side effects (53%), self‐care (51%), and emotional coping (43%). Our analysis identified four clusters of survivors: (a) low needs (n = 123, 42%), (b) mainly physical needs (n = 46, 16%), (c) mainly psychological needs (n = 57, 20%), and (d) both physical and psychological needs (n = 66, 23%). Compared with cluster 1, those in clusters 2, 3, and 4 were younger (p < .03), those in clusters 3 and 4 had higher levels of psychological distress (p < .05), and those in clusters 2 and 4 reported higher levels of fatigue (p < .05).Conclusion.Unmet needs among cancer survivors are prevalent; however, a substantial group of survivors report low or no health care needs. The wide variation in health care needs among cancer survivors suggests a need to screen all patients, followed by tailored interventions in clinical care delivery and research.Implications for Practice.The characterization of patients as having few needs, predominantly physical needs, predominantly psychological needs, or substantial needs that are both physical and psychological provides a productive framework for clinical care of cancer survivors and to guide further research in this field. Further research is needed to define the tailored information and services appropriate for each group of patients and to define optimal screening tools to efficiently identify the needs of individuals in oncology practice.

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Interpretation of Results from Under‐accruing Studies

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Effect of calcium lignosulfonate supplementation on metabolic profiles of confined lambs

Abstract

This study aimed to evaluate the effect of calcium lignosulfonate associated with whole cottonseed in high-concentrate diets for sheep. Eight Dorper crossbred sheep with an average live weight of 42.5 ± 1.70 kg were assigned to two 4 × 4 Latin squares. The following experimental diets were evaluated: control diet (without calcium lignosulfonate) and diets with inclusion of 50, 100, and 150 g of calcium lignosulfonate/kg fresh matter. Diets were composed of soybean meal, ground corn, and whole cottonseed. Feed intake, digestibility, metabolic characteristics, and feeding behavior were evaluated. The intake of nutritional components did not show significant differences as a function of the lignosulfonate levels in the diet; however, the increase in calcium lignosulfonate levels linearly decreased the dry matter digestibility. Rumen ammonia nitrogen concentrations decreased linearly as the lignosulfonate levels in the diets were increased. There was no effect of lignosulfonate levels on blood parameters or feeding behavior of the animals. The use of lignosulfonate associated with cottonseed decreases the digestibility of dry matter and the concentration of rumen ammonia nitrogen, but does not change the intake of nutritional components, the blood parameters, or the feeding behavior of sheep.

https://ift.tt/2I3TBPi

A characterization of pro-inflammatory cytokines in dextran sulfate sodium-induced chronic relapsing colitis mice model

Publication date: July 2018
Source:International Immunopharmacology, Volume 60
Author(s): Yan-hong Li, Rosenstein Adam, Jean-Frederic Colombel, Zhao-xiang Bian
Repeated cycles of dextran sulfate sodium (DSS) administration in mice, inducing chronic relapsing colitis, have been used to mimic human ulcerative colitis (UC). However, no systematic characterization of pro-inflammatory cytokines in these DSS mice has been reported. In this study, the development of colitis was examined by assessment of the disease severity and inflammation in the colon of C57BL/6 mice that received DSS. ELISA was used to analyze the levels of pro-inflammatory cytokines in serum, colon, spleen and supernatant of cultured splenocytes. mRNA levels of the above cytokines in colon and mesenteric lymph node (MLN) were measured with RT-PCR. The mice receiving three cycles of 2% DSS over a 43-day period showed a fluctuating appearance of diarrhea and bloody feces, and a significant reduction in body weight and colon length. When compared with normal control mice, an increase in TNF-α level in serum was detected in the DSS mice, along with a decrease in the amounts of TNF-α, IL-17, IL-1β and IL-6 in the colonic tissue. However, mRNA levels of these cytokines were found to be significantly increased in the colon while decreased in the MLN of the colitis mice. Further, the ELISA assay suggested a pronounced increase of TNF-α production by cultured splenocytes with PMA/ionomycin re-stimulation but no increase in its presence in spleen tissue upon DSS challenge. In conclusion, we have systematically demonstrated the dysregulation of pro-inflammatory cytokines in the DSS-induced chronic relapsing colitis model, which will provide markers to test emerging therapeutic strategies by this model.



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Efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR–TKI treatment in elderly patients with non-small-cell lung cancer harboring sensitive EGFR mutations

Abstract

Purpose

Epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR–TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR–TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR–TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations.

Methods

We retrospectively evaluated the clinical effects and safety profiles of second-line cytotoxic drug chemotherapy after first-line EGFR–TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Between April 2008 and December 2015, 78 elderly patients with advanced NSCLC harboring sensitive EGFR mutations received first-line EGFR–TKI at four Japanese institutions. Baseline characteristics, regimens, responses to first- and second-line treatments, whether or not patients received subsequent treatment, and if not, the reasons for non-administration were recorded.

Results

Overall, 20 patients with a median age of 79.5 years (range 75–85 years) were included in our analysis. The overall response, disease control, median progression-free survival, and overall survival rates were 15.0, 60.0%, 2.4, and 13.2 months, respectively. Common adverse events included leukopenia, neutropenia, anemia, thrombocytopenia, malaise, and anorexia. Major grade 3 or 4 toxicities included leukopenia (25.0%) and neutropenia (45.0%). No treatment-related deaths were noted.

Conclusion

Second-line cytotoxic drug chemotherapy after first-line EGFR–TKI treatment among elderly patients with NSCLC harboring sensitive EGFR mutations was effective and safe and showed equivalent outcomes to first-line cytotoxic drug chemotherapy.

https://ift.tt/2rqsGqu

Predictors of dental plaque and gingivitis in patients receiving integrated dental treatment—a longitudinal retrospective study

Abstract

Objectives

The identification of predictors of supragingival biofilm accumulation may improve the results of therapeutic strategies for dental caries and periodontal diseases in general clinical practice. This study aimed to determine predictors of changes in visible plaque (VP) and gingival bleeding (GB) during integrated dental care.

Materials and methods

A retrospective longitudinal study was conducted by a census of patients receiving integrated dental care in a general clinical practice ambulatory at the Federal University of Rio Grande do Sul (Brazil). The sample comprised 91 charts of patients attended over a 6-months period. Gender, age, patient's main complaint, oral hygiene pattern, and clinical data were recorded from charts for the last two dental visits in the ambulatory. Changes in VP and GB were modeled by multiple linear regression and beta coefficients (b) were reported.

Results

The mean follow-up time was 13 months. Significant reductions in VP (32.8 ± 27.9 to 17.4 ± 19.4%; p < 0.001) and GB (27.1 ± 23.8 to 18.5 ± 17.3%; p < 0.001) were observed. Higher plaque reductions were predicted by higher baseline VP levels (p = 0.02), shorter time (< 12 months) elapsed between VP recordings (b = 14.1%, p = 0.02), interproximal cleansing (b = 11.9%, p = 0.03), lower number of sessions for oral hygiene instruction (b = 13.7%, p = 0.02), and presence of pockets ≥ 6 mm (b = − 12.4%, p = 0.02). GB was predicted by time of follow-up > 12 months and baseline VP.

Conclusions

Plaque and gingivitis improved in patients under integrated dental care. Factors related to motivation, oral hygiene practices, and baseline periodontal status might be used as predictors of VP and GB changes.

Clinical relevance

Visible plaque and gingivitis reduced in a sample of patients treated under integrated dental care. Some predictors may determine for which patients the treatment may be maximize and those who will need greater efforts to achieve the therapeutic goal for oral hygiene.

https://ift.tt/2ruF4oy

Production of palm kernel shell-based activated carbon by direct physical activation for carbon dioxide adsorption

Abstract

The feasibility of biomass-based activated carbons has received a huge attention due to their excellent characteristics such as inexpensiveness, good adsorption behaviour and potential to reduce a strong dependency towards non-renewable precursors. Therefore, in this research work, eco-friendly activated carbon from palm kernel shell that has been produced from one-stage physical activation by using the Box-Behnken design of Response Surface Methodology is highlighted. The effect of three input parameters—temperature, dwell time and gas flow rate—towards product yield and carbon dioxide (CO₂) uptake at room temperature and atmospheric pressure are studied. Model accuracy has been evaluated through the ANOVA analysis and lack-of-fit test. Accordingly, the optimum condition in synthesising the activated carbon with adequate CO₂ adsorption capacity of 2.13 mmol/g and product yield of 25.15 wt% is found at a temperature of 850 °C, holding time of 60 min and CO₂ flow rate of 450 cm³/min. The synthesised activated carbon has been characterised by diverse analytical instruments including thermogravimetric analyser, scanning electron microscope, as well as N₂ adsorption-desorption isotherm. The characterisation analysis indicates that the synthesised activated carbon has higher textural characteristics and porosity, together with better thermal stability and carbon content as compared to pristine palm kernel shell. Activated carbon production via one-step activation approach is economical since its carbon yield is within the industrial target, whereas CO₂ uptake is comparable to the synthesised activated carbon from conventional dual-stage activation, commercial activated carbon and other published data from literature.

https://ift.tt/2jJFPa2

A laboratory study investigating the effects of dilution by precipitation on dissolved inorganic carbon and stable isotope evolution in surface waters

Abstract

Surface waters are a major pathway of carbon cycling between the atmosphere and the earth's surface. Yet studies describing water column processes that affect carbon cycling do not consider the effects of dilution by precipitation. In this study, we conducted a laboratory experiment in which we prepared undiluted (100%) and snowmelt diluted 25, 50, and 75% by volume of samples of NaHCO₃ solution and lake and river water and then exposed them to the laboratory atmosphere for up to 1000 h. We aim to determine how dilution by precipitation followed by water-atmosphere CO_2(g) interaction affects DIC and δ¹³C_DIC evolution. Dilution resulted in decreased pH, solutes, and DIC concentrations according to the dilution proportion. The decreased pH perturbed the carbonate equilibrium resulting in CO_2(g) outgassing. In all the samples, there was continuous enrichment in the δ¹³C_DIC composition. Isotopic evolution by CO_2(g) loss in the > 50% snowmelt-diluted samples lasted for about 10 h, while it took about 400 h for the diluted samples to evolve to a similar isotopic composition as the undiluted samples. Our laboratory results suggest that the effects of precipitation dilution should not be ignored in studying DIC evolution in surface waters during periods where precipitation dilution exceeds 50% by volume.

https://ift.tt/2I9t2bd

Assessment of the Risk of Antiangiogenic Agents Before and After Surgery

Publication date: Available online 8 May 2018
Source:Cancer Treatment Reviews
Author(s): Christina E. Bailey, Alexander A. Parikh
Angiogenesis plays a critical role in the growth, progression, and metastasis of numerous solid tumor types, and thus, antiangiogenic agents have been studied for many years as potential therapeutic agents. Many different antiangiogenic agents, including monoclonal antibodies and multi-targeted tyrosine kinase inhibitors (TKIs), have been approved for various oncology indications, and promising clinical activity has been demonstrated. However, some of these agents have also been associated with serious safety concerns. Because angiogenesis is an important step in the wound healing process, agents targeting the angiogenesis pathway may interfere with wound healing, thus increasing the risk of surgical wound complications, such as dehiscence, surgical site bleeding, and wound infection. Nevertheless, antiangiogenic agents can be safely used in the perioperative setting if oncologists and surgeons are educated on the biology and pharmacokinetics of these agents. This review discusses the available published literature regarding surgical complications associated with the use of antiangiogenic agents and provides updated clinical recommendations on the optimal timing between surgery and antiangiogenic therapy. Due to the paucity of data surrounding this topic, current and future clinical trials need to evaluate prospectively the potential risks for surgical complications associated with antiangiogenic therapies to establish specific guidelines for their safe and effective use within the surgical oncology community.

Graphical abstract

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Toward innovative combinational immunotherapy: a systems biology perspective

Publication date: Available online 8 May 2018
Source:Cancer Treatment Reviews
Author(s): Xue-Tao Li, Jin-Ji Yang, Yi-Long Wu, Jun Hou
The treatment of non-small-cell lung cancer (NSCLC) has advanced significantly in the last decades. Especially immune checkpoint inhibitors have shown inconceivable effect on enhancing host anti-tumor activity in NSCLC. However, the limitation of checkpoint blockade monotherapy seems unavoidable in most of the NSCLC patients and only ∼20% of them achieved response to monotherapy with immune checkpoint inhibitors. Thus combining immune checkpoint inhibitors with other agents with different action mechanisms holds a promise to revitalize NSCLC treatment, such as the combination of checkpoint inhibitors with angiogenesis inhibitors, or with chemotherapy, as well as the combination of two checkpoint inhibitors. Recently, various combinational strategies have been explored to setup promising combination regimens and to understand the action mechanisms. In this review, we summarize the suspected synergistic mechanisms of several combinational approaches by reviewing the available preclinical and clinical data. Then we discuss in light of the current knowledge of cancer biology and systems biology the important facets to be examined when setting up a framework for developing immunotherapy-based combination strategies.



https://ift.tt/2HZVjoN

Characteristics and batch experiments of acid- and alkali-modified corncob biomass for nitrate removal from aqueous solution

Abstract

In this study, modified biochar was adopted as an adsorbent for the nitrate removal in aqueous solutions. Raw material was impregnated in sulfuric acid (H₂SO₄, 1 mol/L) and sodium hydroxide (NaOH, 2 mol/L) separately and then prepared at 600 °C. After treated with acid, the BET specific surface area was much higher than that of unmodified and alkali-modified biochars. The low adsorption capacity and specific surface area of alkali-modified biochar may be due to the precipitate on the surface according to the results of XRD. In addition, the C–OH and C–H functional groups played a major part during adsorption progress. The batch experiments demonstrated that the acid-modified biochar exhibited a more excellent absorbability (12.75 mg/g) under the circumstance of neutral solution and room temperature. The maximum adsorption capacity of MSA-CC was 34.20 mg/g, which was about 2.4 times higher than that of the unmodified. Low pH value can provide positive charge conditions to enhance the adsorption capacity. Overall, the biochar with excellent pore structure and chargeable functional group can be a potential application for nitrate removal which was low cost and effective. After treated with acid, biochar could adsorb negative charge species like nitrate due to electrostatic interaction.

Graphical abstract

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Degradation of carbendazim in water via photo-Fenton in Raceway Pond Reactor: assessment of acute toxicity and transformation products

Abstract

This study aimed at investigating the degradation of fungicide carbendazim (CBZ) via photo-Fenton reactions in artificially and solar irradiated photoreactors at laboratory scale and in a semi-pilot scale Raceway Pond Reactor (RPR), respectively. Acute toxicity was monitored by assessing the sensibility of bioluminescent bacteria (Aliivibrio fischeri) to samples taken during reactions. In addition, by-products formed during solar photo-Fenton were identified by liquid chromatography coupled to mass spectrometry (UFLC-MS). For tests performed in lab-scale, two artificial irradiation sources were compared (UV_{λ > 254nm} and UV-Vis_{λ > 320nm}). A complete design of experiments was performed in the semi-pilot scale RPR in order to optimize reaction conditions (Fe²⁺ and H₂O₂ concentrations, and water depth). Efficient degradation of carbendazim (> 96%) and toxicity removal were achieved via artificially irradiated photo-Fenton under both irradiation sources. Control experiments (UV photolysis and UV-Vis peroxidation) were also efficient but led to increased acute toxicity. In addition, H₂O₂/UV_{λ > 254nm} required longer reaction time (60 minutes) when compared to the photo-Fenton process (less than 1 min). While Fenton's reagent achieved high CBZ and acute toxicity removal, its efficiency demands higher concentration of reagents in comparison to irradiated processes. Solar photo-Fenton removed carbendazim within 15 min of reaction (96%, 0.75 kJ L⁻¹), and monocarbomethoxyguanidine, benzimidazole isocyanate, and 2-aminobenzimidazole were identified as transformation products. Results suggest that both solar photo-Fenton and artificially irradiated systems are promising routes for carbendazim degradation.

https://ift.tt/2FYCRa6

Influence of composted poultry manure and irrigation regimes on some morpho-physiology parameters of maize under semiarid environments

Abstract

Poultry manure (PM), a rich source for crop nutrients, is produced in ample quantities worldwide. It provides necessary nutrient to soil and has a potential to improve plant water holding availability under semiarid environment. The effect of composted poultry manure (CPM) and irrigation regimes on morpho-physiology of selective maize (Zea mays L.) hybrids (H₁ = drought tolerant, H₂ = drought sensitive) was investigated in this study. Two field experiments were conducted during 2010 and 2011 under randomized complete block design with split split-plot arrangements and three replications of each treatment. Irrigation regimes (I₁ = 300, I₂ = 450, I₃ = 600 mm) were kept in main plots; the two maize hybrids (H₁ and H₂) in sub-plots and nutrient levels (L₁ = recommended rate of NPK (control), L₂ = 8 t ha⁻¹ CPM, L₃ = 10 t ha⁻¹ CPM, and L₄ = 12 t ha⁻¹ CPM) were arranged in sub sub-plots. The drought tolerant hybrid showed best growth under all treatments. Results revealed that maximum leaf area index (LAI) was recorded with the application of the recommended dose of NPK. Low irrigation regimes (I₁ and I₂) highly significantly (P < 0.01) reduced the photosynthesis and transpiration rate in both hybrids while application of 12 t ha⁻¹ CPM was able to partially alleviate the effect of water stress on these parameters. Resultantly, the application of 12 t ha⁻¹ CPM enhanced the plant growth and increased grain yield (21%; 4.17 vs 5.27) under limited water availability (I₂L₄) as compared to the recommended dose of NPK (I₂L₁). However, the nutrient application under control treatment had maximum grain yield. Therefore, shortage of water for maize production might be partially alleviated by the application of 12 t ha⁻¹ CPM.

https://ift.tt/2jJwu1S

Comparisons of three plant species in accumulating polycyclic aromatic hydrocarbons (PAHs) from the atmosphere: a review

Abstract

Plant leaves play a key role in the accumulation of PAHs, as they are able to capture PAHs from the air. In this paper, the mechanism, including absorption and adsorption, for plants to scavenge PAHs from the air was reviewed. Moreover, the differences of PAHs accumulating capability are mainly compared among three representative plant species, including pine needles, Holm oak leaves, and moss. On the whole, it is shown that oak leaves present the strongest PAHs accumulating capability for total PAHs among three plants species. Oak leaves and pine needles show higher accumulating tendency for light and medium molecular weight PAHs, whereas moss presents stronger accumulating tendency for heavy molecular weight PAHs. Environmental factors (i.e., temperature, seasonality, and photolysis) also account for the process of PAHs transferred from air to plants. With the temperature climbing, the concentration of PAHs in the air will increase. Due to the meteorological conditions and the human activities changed with seasons, it was shown that the PAHs were greatly accumulated in leaf surface in winter than in summer. Photolysis was also able to influence the PAHs on leaf surface, which are significant to this process. In conclusion, oak, pine, and moss can be used to filter PAHs when considering urban landscaping. Besides combining the traditional analytical methods with in situ determination, there might be able to provide a novel method to further study the specific absorption mechanisms. The accumulation of PAHs in crop leaf surface related to the application of surfactants is also worth studying.

https://ift.tt/2FVOLla

Does democratic transition reduce carbon intensity? Evidence from Indonesia using the synthetic control method

Abstract

Despite growing concern about the low-carbon economic development, little is known about the role of political institutions, democracy, or the absence thereof, in controlling carbon intensity (carbon dioxide emissions per unit of GDP). This paper estimates the causal effects of democratic transition in Indonesia on its national carbon emission intensity. The synthetic control method is adopted to handle both time-invariant and time-variant confounding heterogeneity. Results show that Indonesia's democratic transition increases on average 0.24 kg carbon dioxide emissions per constant 2005 US dollar in the post-transition period (1999–2010), a rise of approximately 25.34%. The placebo tests indicate this causal effect is significant and the leave-one-out sensitivity check also demonstrates its robustness. The evidence of Indonesia suggests that democratic transition may serve to intensify, rather than mitigate, the emissions of carbon dioxide. Therefore, policymakers should pay more attentions to the contextual fit of democratic transition.

https://ift.tt/2KN1aeH

Syntactic processing in music and language: Effects of interrupting auditory streams with alternating timbres

Publication date: Available online 8 May 2018
Source:International Journal of Psychophysiology
Author(s): Anna Fiveash, William F. Thompson, Nicholas A. Badcock, Genevieve McArthur
Both music and language rely on the processing of spectral (pitch, timbre) and temporal (rhythm) information to create structure and meaning from incoming auditory streams. Previous behavioural results have shown that interrupting a melodic stream with unexpected changes in timbre leads to reduced syntactic processing. Such findings suggest that syntactic processing is conditional on successful streaming of incoming sequential information. The current study used event-related potentials (ERPs) to investigate whether (1) the effect of alternating timbres on syntactic processing is reflected in a reduced brain response to syntactic violations, and (2) the phenomenon is similar for music and language. Participants listened to melodies and sentences with either one timbre (piano or one voice) or three timbres (piano, guitar, and vibraphone, or three different voices). Half the stimuli contained syntactic violations: an out-of-key note in the melodies, and a phrase-structure violation in the sentences. We found smaller ERPs to syntactic violations in music in the three-timbre compared to the one-timbre condition, reflected in a reduced early right anterior negativity (ERAN). A similar but non-significant pattern was observed for language stimuli in both the early left anterior negativity (ELAN) and the left anterior negativity (LAN) ERPs. The results suggest that timbre disruptions to auditory streaming reduce syntactic processing for music.



https://ift.tt/2FVGw8R

High definition-transcranial direct current stimulation changes older adults' subjective sleep and corresponding resting-state functional connectivity

Publication date: Available online 8 May 2018
Source:International Journal of Psychophysiology
Author(s): Jing Sheng, Chao Xie, Dong-qiong Fan, Xu Lei, Jing Yu
With advanced age, older adults show functional deterioration in sleep. Transcranial direct current stimulation (tDCS), a noninvasive brain stimulation, modulates individuals' behavioral performance in various cognitive domains. However, the modulation effect and neural mechanisms of tDCS on sleep, especially for the elderly population are not clear. Here, we aimed to investigate whether high-definition transcranial direct current stimulation (HD-tDCS) could modulate community-dwelling older adults' subjective sleep and whether these potential improvements are associated with the large-scale brain activity alterations recorded by functional magnetic resonance imaging. Thirty-one older adults were randomly allocated to the HD-tDCS group and the control group. HD-tDCS was applied for 25 min at 1.5 mA per day for two weeks. The anode electrode was placed over the left dorsolateral prefrontal cortex, surrounded by 4 cathodes at 7 cm radius. All participants completed sleep neuropsychological assessments and fMRI scans individually before and after intervention. Behaviorally, we observed a HD-tDCS-induced enhancement of older adults' sleep duration. On the aspect of the corresponding neural alterations, we observed that HD-tDCS decreased the functional connectivity between the default mode network (DMN) and subcortical network. More importantly, the decoupling connectivity of the DMN-subcortical network was correlated with the improvements of subjective sleep in the HD-tDCS group. Our findings add novel behavioral and neural evidences about tDCS-induced sleep improvement in community-dwelling older adults. With further development, tDCS may be used as an alternative treatment for sleep disorders and alleviate the dysfunction of brain networks induced by aging.



https://ift.tt/2KLvdDL

Hallazgos de la PET/TC con 18F-FDG en un paciente con paraganglioma: activación de la grasa parda debido a estimulación adrenérgica

Publication date: Available online 7 May 2018
Source:Revista Española de Medicina Nuclear e Imagen Molecular
Author(s): E. Özdemir, Z. Kandemir, M. Keskin, N. Yildirim, D. Özdemir, S. Turkolmez




https://ift.tt/2IsWBZ3

Removal of urea from dilute streams using RVC/nano-NiO x -modified electrode

Abstract

Reticulated vitreous carbon (RVC), a high surface area electrode (40 cm²/cm³), has been modified with nickel oxide nanoparticles (nano-NiO_x ) and used for electrochemical oxidation of urea from alkaline solution. For the cyclic voltammetry measurements, the used dimensions are 0.8 cm × 0.8 cm × 0.3 cm. The purpose was to offer high specific surface area using a porous open network structure to accelerate the electrochemical conversion. NiO_x nanoparticles have been synthesized via an electrochemical route at some experimental conditions. The morphological, structural, and electrochemical properties of the RVC/nano-NiO_x are characterized by using scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), cyclic voltammetry (CV), and potentiostatic measurements. The fabricated electrode, RVC/nano-NiO_x , demonstrates high electrocatalytic activity towards urea oxidation in an alkaline electrolyte. The onset potential of the RVC/nano-NiO_x compared to that of the planar GC/NiO_x is shifted to more negative value with higher specific activity. The different loadings of the NiO_x have a substantial influence on the conversion of urea which has been evaluated from concentration-time curves. The urea concentration decreases with time to a limit dependent on the loading extent. Maximum conversion is obtained at 0.86 mg of NiO_x per cm³ of the RVC matrix.

https://ift.tt/2rtZb7l

Screening optimal substrates from Erhai lakeside for Ottelia acuminata (Gagnep.) Dandy, an endangered submerged macrophyte in China

Abstract

Because of the unstable hydrodynamic conditions in the wild, the endangered aquatic plant should be cultivated first in constructed wetlands for the protection and expansion of germplasm resources. Ottelia acuminata (Gagnep.) Dandy has become extinct in Erhai Lake, Yunnan province, China. In order to optimize substrates for this species to artificial cultivation, the native substrate (sandy soils) and the other three representative ones (red paddy soils, alluvial paddy soils, and purple paddy soils) collected from Erhai lakeside were applied to cultivate O. acuminata for 50 days. Multi indicators, such as antioxidant enzymes activity, malondialdehyde and chlorophyll-α concentration, and relative growth rate of O. acuminata, were discussed and statistically analyzed to classify the substrates. The results suggested that even disregarding the physiology significance of these indicators, hierarchical clustering analysis had high efficiency on optimizing substrates. Although various single indexes suggested different optimal substrates for macrophyte growth, red paddy soil was never excluded out the optimal substrate classes. Further study is needed to assess the substrates optimization functionalities of these indicators. This study offers amounts of physiology data and an effective method to optimize substrates of O. acuminata. It is helpful for environmental scientists and ecological engineers to conduct the similar study on endangered species.

https://ift.tt/2wlnEAx

Strategies to Improve Image Quality on Dual-Energy Computed Tomography

Publication date: Available online 4 May 2018
Source:Radiologic Clinics of North America
Author(s): Bhavik N. Patel, Daniele Marin

Teaser

Dual-energy computed tomography (DECT) offers several advantages over conventional single-energy CT. These advantages include improved image quality, beam hardening correction, and metal artifact reduction. Additionally, DECT allows derivation of quantitative information through material decomposition analysis. Although newer third-generation rapid-kilovolt switching and dual-source DECT scanners have significantly improved in image quality and workflow compared with initial iterations and early scanners, sources of potential image quality degradation can exist secondary to the inherent capabilities in which the image acquisition occurs.


https://ift.tt/2rpJL30

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 MRI feature tracking strain is prognostic for all-cause mortality in AL amyloidosis | Jeffery E. Illman, Shivaram P. Arunachalam, Arvin Arani, Ian Cheng-Yi Chang, James F. Glockner, Angela Dispenzieri, Martha Grogan & Philip A. Araoz Pages: 1-8 | DOI: 10.1080/13506129.2018.1465406 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.

Delivery of adapalene using a novel topical gel based on tea tree oil nano-emulsion: Permeation, antibacterial and safety assessments

Publication date: 30 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 120
Author(s): Roqya Najafi-Taher, Behnaz Ghaemi, Amir Amani
The aim of present study was to design and optimize 0.1% adapalene loaded nano-emulsion to improve the drug efficacy and increase its user compliance. Effect of type and concentration of surfactants was studied on size of 0.1% adapalene loaded nano-emulsion. Optimized formulation was then evaluated for particle size, polydispersity index, morphology, viscosity, and pH. Subsequently, 1% carbopol® 934 was incorporated to the optimized formulation for preparation of its gel form. The efficacy and safety of 0.1% adapalene loaded nano-emulsion gel was assessed compared to marketed gel containing 0.1% adapalene. In-vitro studies showed that adapalene permeation through the skin was negligible in both adapalene loaded nano-emulsion gel and adapalene marketed gel. Furthermore, drug distribution studies in skin indicated higher retention of adapalene in the dermis in adapalene loaded nano-emulsion gel compared with adapalene marketed gel. Antibacterial activity against Propionibacterium acnes showed that adapalene loaded nano-emulsion is effective in reducing minimum inhibitory concentration of the formulation in comparison with tea tree oil nano-emulsion, and pure tea tree oil.In vivo skin irritation studies showed absence of irritancy for adapalene loaded nano-emulsion gel. Also, blood and liver absorption of the drug, histological analysis of liver and liver enzyme activity of rats after 90 days' treatment were investigated. No drug was detected in blood/liver which in addition to an absence of any adverse effect on liver and enzymes showed the potential of adapalene loaded nano-emulsion gel as a novel carrier for topical delivery of adapalene.

Graphical abstract

https://ift.tt/2Iob0FH

Biopharmaceutical evaluation of surface active ophthalmic excipients using in vitro and ex vivo corneal models

Publication date: 30 July 2018
Source:European Journal of Pharmaceutical Sciences, Volume 120
Author(s): Marina Juretić, Biserka Cetina-Čižmek, Jelena Filipović-Grčić, Anita Hafner, Jasmina Lovrić, Ivan Pepić
The objective of this study was to systematically investigate the effects of surface active ophthalmic excipients on the corneal permeation of ophthalmic drugs using in vitro (HCE-T cell-based model) and ex vivo (freshly excised porcine cornea) models. The permeation of four ophthalmic drugs (i.e., timolol maleate, chloramphenicol, diclofenac sodium and dexamethasone) across in vitro and ex vivo corneal models was evaluated in the absence and presence of four commonly used surface active ophthalmic excipients (i.e., Polysorbate 80, Tyloxapol, Cremophor® EL and Pluronic® F68). The concentration and self-aggregation-dependent effects of surface active ophthalmic excipients on ophthalmic drug permeability were studied from the concentration region where only dissolved monomer molecules of surface active ophthalmic excipients exist, as well as the concentration region in which aggregates of variable size and dispersion are spontaneously formed. Neither the surface active ophthalmic excipients nor the ophthalmic drugs at all concentrations that were tested significantly affected the barrier properties of both corneal models, as assessed by transepithelial electrical resistance (TEER) monitoring during the permeability experiments. The lowest concentration of all investigated surface active ophthalmic excipients did not significantly affect the ophthalmic drug permeability across both of the corneal models that were used. For three ophthalmic drugs (i.e., chloramphenicol, diclofenac sodium and dexamethasone), depressed in vitro and ex vivo permeability were observed in the concentration range of either Polysorbate 80, Tyloxapol, Cremophor® EL or Pluronic® F68, at which self-aggregation is detected. The effect was the most pronounced for Cremophor® EL (1 and 2%, w/V) and was the least pronounced for Pluronic® F68 (1%, w/V). However, all surface active ophthalmic excipients over the entire concentration range that was tested did not significantly affect the in vitro and ex vivo permeability of timolol maleate, which is the most hydrophilic ophthalmic drug that was investigated. The results of the dynamic light scattering measurements point to the association of ophthalmic drugs with self-aggregates of surface active ophthalmic excipients as the potential mechanism of the observed permeability-depressing effect of surface active ophthalmic excipients. A strong and statistically significant correlation was observed between in vitro and ex vivo permeability of ophthalmic drugs in the presence of surface active ophthalmic excipients, which indicates that the observed permeability-altering effects of surface active ophthalmic excipients were comparable and were mediated by the same mechanism in both corneal models.

Graphical abstract

https://ift.tt/2wsvdWc

Functional non-homologous end joining pattern triggered by CRISPR/Cas9 in human cells

Publication date: Available online 8 May 2018
Source:Journal of Genetics and Genomics
Author(s): Fayu Yang, Xianglian Ge, Xiubin He, Xiexie Liu, Chenchen Zhou, Huihui Sun, Junsong Zhang, Jia Qu, Junzhao Zhao, Zongming Song, Changbao Liu, Feng Gu




https://ift.tt/2wulQp4

Effects of Dahuang zhechong pill on doxorubicin-resistant SMMC-7721 xenografts in mice

Publication date: 10 August 2018
Source:Journal of Ethnopharmacology, Volume 222
Author(s): Li Wu, Ke Xing Cao, Zi Hui Ni, Wei Dong Li, Zhi Peng Chen, Hai Bo Cheng, Xiao Liu
Ethnopharmacological relevanceDahuang zhechong pill (DHZCP) is a famous traditional Chinese medicinal prescription from the "Synopsis of Prescriptions of the Golden Chamber (Jin Kui Yao Lue)",Lue)", an ancient Chinese medical classic. DHZCP is commonly used for clinical treatment of liver cancer by promoting blood circulation to dissolve blood stasis and by removing pathogenic vegetations.vegetations. DHZCP-based treatment has been derived from Traditional Chinese Medicine (TCM) and is officially recorded in the Chinese Pharmacopoeia.Aim of the studyThe aim of this study was to investigate the ability of DHZCP to reverse doxorubicin (DOX) resistance of SMMC-7721 cells in a xenograft mouse model, and to explore the underlying mechanisms.Materials and methodsLiquid chromatography–mass spectrometry was used to verify the composition of DHZCP. H&E staining was used to observe the pathological changes in hepatocellular carcinoma samples. Intracellular DOX accumulation was observed as intrinsic fluorescence by microscopy. Cell apoptosis was detected by the TUNEL assay. Human antibody arrays were used to analyze the expression of apoptotic- and angiogenic-related proteins. ATP levels were assessed and western blots were used to detect the protein expression of key enzymes of energy metabolism.ResultsDHZCP significantly reduced the tumor volume and weight of subcutaneous xenografts of drug-resistant hepatoma cells, and combining DHZCP with lower doses of DOX significantly increased the content of DOX in tumor tissue, increased the apoptosis of hepatoma cells, and reversed Dox resistance. With respect to 43 apoptosis-associated proteins, DHZCP regulated the expression of 5 of them. When combined with low-dose DOX, the expression of 40 apoptosis-related proteins was significantly altered. With respect to 23 angiogenesis-associated proteins, DHZCP upregulated the expression of endostatin and inhibited the expression of matrix metallopeptidase 9. When combined with low-dose DOX, DHZCP significantly downregulated protein expression of urokinase receptor, as well as vascular endothelial growth factor receptors 2 and 3. Especially, DHZCP significantly inhibited the expression of key enzymes of the tricarboxylic acid cycle and of oxidative phosphorylation, reducing the level of ATP in tumor tissue.ConclusionsDHZCP inhibited the growth of DOX-resistant hepatocellular carcinoma subcutaneous xenografts in nude mice and promoted increased apoptosis caused by DOX, thus reversing DOX resistance. This was associated with a decline in energy metabolism and regulated expression of pro-apoptotic proteins.

Graphical abstract

https://ift.tt/2wmic0n