Extracellular polymeric substances with metal adsorption capacity produced by Pseudoalteromonas sp. MER144 from Antarctic seawater

Abstract

The EPS-producing Pseudoalteromonas sp. MER144 was selected among 606 isolates from Antarctic seawater due to its evident slimy appearance on agar plates. The production of EPSs was enhanced by a step-by-step approach varying the carbon source, substrate and NaCl concentrations, temperature, and pH. Optimal conditions for the EPS production resulted at temperature of 4 °C and pH 7, with addition of 2% sucrose (w/v) and 3% NaCl (w/v). EPSs produced under optimal conditions were chemically characterized, resulting in a moderate carbohydrate content (35%), uronic acids (14%), and proteins (12%). Monosaccharide composition was estimated to be Glu:Man:GluN:Ara:GluA:GalA:Gal (1:0.36:0.26:0.06:0.06:0.05:0.03), while the estimated molecular weight was about 250 kDa. The addition of sucrose in the culture medium, by stimulating the EPS production, allowed MER144 to tolerate higher concentrations of mercury and cadmium. This finding was probably dependent on the presence of uronic acids and sulfate groups, which can bind cations, in the extracted EPSs. Monitoring EPS production under optimal conditions at different concentrations of mercury and cadmium revealed that EPS amounts increased at increasing heavy metal concentrations, indicating an adaptation to the stress conditions tested.

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Current state of yusho and prospects for therapeutic strategies

Abstract

The mass food poisoning incident yusho occurred in Japan in 1968. It was caused by the ingestion of rice bran oil contaminated with polychlorinated biphenyls and various dioxins and dioxin-like compounds including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDFs). Notably, PCDFs were found to contribute to approximately 65% of the total toxicity equivalent in the blood of yusho patients. Lipophilic dioxins are retained in the body for a longer period than previously estimated. Victims suffered from characteristic skin manifestations associated with non-specific systemic symptoms, neurological symptoms, and respiratory symptoms. The severe symptoms seen in the initial phase subsequently faded, but recently, improvements have scarcely been observed. The Yusho Group has been researching treatments for this condition. Several clinical trials with chelating agents or dietary fibers aimed at accelerating the excretion of compounds. While some treatments increased dioxin excretion, none provided satisfactory symptom relief. Concurrently, various phytochemicals and herbal extracts have been found to possess biological activities that suppress dioxin-induced toxicity via aryl hydrocarbon receptor or activate the antioxidant nuclear factor-erythroid 2-related factor-2 (NRF2) signal pathway, making them promising therapeutic candidates. Here, we summarize the current status of yusho and findings of clinical trials for yusho patients and discuss the treatment prospects.

http://ift.tt/2nk2gar

The Zygotic Transition Is Initiated in Unicellular Plant Zygotes with Asymmetric Activation of Parental Genomes

Publication date: 6 November 2017
Source:Developmental Cell, Volume 43, Issue 3
Author(s): Sarah N. Anderson, Cameron S. Johnson, Joshua Chesnut, Daniel S. Jones, Imtiyaz Khanday, Margaret Woodhouse, Chenxin Li, Liza J. Conrad, Scott D. Russell, Venkatesan Sundaresan
The zygotic transition, from a fertilized egg to an embryo, is central to animal and plant reproduction. Animal embryos depend upon maternally provided factors until zygotic genome activation (ZGA). In plants, the timing and parental genome contributions to ZGA are unresolved. Here, we use the flowering plant Oryza sativa (rice) to characterize transcriptomes of time-staged isogenic and hybrid zygotes following fertilization. Large-scale transcriptomic changes were observed in unicellular zygotes, including upregulation of S-phase genes, a characteristic of ZGA. The parental contributions to ZGA were highly asymmetric. Zygotic transcription was primarily from the maternal genome and included genes for basic cellular processes. Transcription of the paternal genome was highly restricted but unexpectedly included genes encoding putative pluripotency factors expressed at the onset of ZGA. Thus, distinct transcriptional activities are exhibited by the parental genomes during the initiation of embryogenesis, which presumptively derive from divergent pre-zygotic transcriptional states established in the gametes.

Graphical abstract

Teaser

The transition from maternal to zygotic gene expression is critical to multicellular organism development. Anderson et al. elucidate timing and parental genome contribution to zygotic genome activation (ZGA) in rice. ZGA occurs in the unicellular zygote, with unequal parental contribution where most genes are expressed primarily from the maternal genome.


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Bleb Expansion in Migrating Cells Depends on Supply of Membrane from Cell Surface Invaginations

Publication date: Available online 22 November 2017
Source:Developmental Cell
Author(s): Mohammad Goudarzi, Katsiaryna Tarbashevich, Karina Mildner, Isabell Begemann, Jamie Garcia, Azadeh Paksa, Michal Reichman-Fried, Harsha Mahabaleshwar, Heiko Blaser, Johannes Hartwig, Dagmar Zeuschner, Milos Galic, Michel Bagnat, Timo Betz, Erez Raz
Cell migration is essential for morphogenesis, organ formation, and homeostasis, with relevance for clinical conditions. The migration of primordial germ cells (PGCs) is a useful model for studying this process in the context of the developing embryo. Zebrafish PGC migration depends on the formation of cellular protrusions in form of blebs, a type of protrusion found in various cell types. Here we report on the mechanisms allowing the inflation of the membrane during bleb formation. We show that the rapid expansion of the protrusion depends on membrane invaginations that are localized preferentially at the cell front. The formation of these invaginations requires the function of Cdc42, and their unfolding allows bleb inflation and dynamic cell-shape changes performed by migrating cells. Inhibiting the formation and release of the invaginations strongly interfered with bleb formation, cell motility, and the ability of the cells to reach their target.

Teaser

Blebs are cellular protrusions that play key roles in a range of physiological and disease processes. Employing the primordial germ cells of zebrafish as an in vivo model for cell migration, Goudarzi et al. show that the rapid expansion of protrusions of this type depends on unfolding of membrane invaginations.


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Mitotic Chromosomes: Not So Silent After All

Publication date: 23 October 2017
Source:Developmental Cell, Volume 43, Issue 2
Author(s): H.T. Marc Timmers, C. Peter Verrijzer
Mitotic chromosome condensation is believed to be incompatible with transcription. Palozola et al. (2017) now report in Science that a transcription program is maintained during mitosis and that transcriptional re-activation at mitotic exit is geared to support cell growth rather than cell identity.

Teaser

Mitotic chromosome condensation is believed to be incompatible with transcription. Palozola et al. (2017) now report in Science that a transcription program is maintained during mitosis and that transcriptional re-activation at mitotic exit is geared to support cell growth rather than cell identity.


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Investigating Regeneration

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4





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Mechanochemical Polarization of Contiguous Cell Walls Shapes Plant Pavement Cells

Publication date: 6 November 2017
Source:Developmental Cell, Volume 43, Issue 3
Author(s): Mateusz Majda, Peter Grones, Ida-Maria Sintorn, Thomas Vain, Pascale Milani, Pawel Krupinski, Beata Zagórska-Marek, Corrado Viotti, Henrik Jönsson, Ewa J. Mellerowicz, Olivier Hamant, Stéphanie Robert
The epidermis of aerial plant organs is thought to be limiting for growth, because it acts as a continuous load-bearing layer, resisting tension. Leaf epidermis contains jigsaw puzzle piece-shaped pavement cells whose shape has been proposed to be a result of subcellular variations in expansion rate that induce local buckling events. Paradoxically, such local compressive buckling should not occur given the tensile stresses across the epidermis. Using computational modeling, we show that the simplest scenario to explain pavement cell shapes within an epidermis under tension must involve mechanical wall heterogeneities across and along the anticlinal pavement cell walls between adjacent cells. Combining genetics, atomic force microscopy, and immunolabeling, we demonstrate that contiguous cell walls indeed exhibit hybrid mechanochemical properties. Such biochemical wall heterogeneities precede wall bending. Altogether, this provides a possible mechanism for the generation of complex plant cell shapes.

Teaser

Pavement cells in the leaf epidermis are multi-lobed like jigsaw puzzle pieces. Majda et al. provide evidence through in vivo analyses using atomic force microscopy and computational modeling that mechanical heterogeneities across and along anticlinal cell walls allow wall bending that contributes to lobe formation and these complex cell shapes.


http://ift.tt/2zWaUl9

Localized Lysosome Exocytosis Helps Breach Tissue Barriers

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4
Author(s): Shaohe Wang, Kenneth M. Yamada
Cell invasion across basement membrane barriers is important in both normal development and cancer metastasis. In this issue of Developmental Cell, Naegeli et al. (2017) identify a mechanism for breaching basement membranes. Localized lysosome exocytosis fuels generation of large, invasive cellular protrusions that expand tiny basement membrane openings.

Teaser

Cell invasion across basement membrane barriers is important in both normal development and cancer metastasis. In this issue of Developmental Cell, Naegeli et al. (2017) identify a mechanism for breaching basement membranes. Localized lysosome exocytosis fuels generation of large, invasive cellular protrusions that expand tiny basement membrane openings.


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Osteoblast Production by Reserved Progenitor Cells in Zebrafish Bone Regeneration and Maintenance

Publication date: Available online 2 November 2017
Source:Developmental Cell
Author(s): Kazunori Ando, Eri Shibata, Stefan Hans, Michael Brand, Atsushi Kawakami
Mammals cannot re-form heavily damaged bones as in large fracture gaps, whereas zebrafish efficiently regenerate bones even after amputation of appendages. However, the source of osteoblasts that mediate appendage regeneration is controversial. Several studies in zebrafish have shown that osteoblasts are generated by dedifferentiation of existing osteoblasts at injured sites, but other observations suggest that de novo production of osteoblasts also occurs. In this study, we found from cell-lineage tracing and ablation experiments that a group of cells reserved in niches serves as osteoblast progenitor cells (OPCs) and has a significant role in fin ray regeneration. Besides regeneration, OPCs also supply osteoblasts for normal bone maintenance. We further showed that OPCs are derived from embryonic somites, as is the case with embryonic osteoblasts, and are replenished from mesenchymal precursors in adult zebrafish. Our findings reveal that reserved progenitors are a significant and complementary source of osteoblasts for zebrafish bone regeneration.

Graphical abstract

Teaser

Ando et al. identify osteoblast progenitor cells (OPCs) in zebrafish and find that OPCs are derived from embryonic somites and are reserved in niches of bone-forming tissues while being replenished from mesenchymal precursors. OPCs migrate from the niches and generate osteoblasts during bone regeneration and maintenance in adult zebrafish.


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Re-cyclin’ Cell-Cycle Components to Make NETs

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4
Author(s): Jean Albrengues, Robert W. Wysocki, Laura Maiorino, Mikala Egeblad
Neutrophil extracellular traps (NETs) are critical for the clearance of large pathogens and are also implicated in thrombosis, autoimmunity, and cancer. In this issue of Developmental Cell, Amulic et al. (2017) show that the terminally differentiated, non-cycling neutrophils repurpose cell-cycle proteins and pathways to form NETs.

Teaser

Neutrophil extracellular traps (NETs) are critical for the clearance of large pathogens and are also implicated in thrombosis, autoimmunity, and cancer. In this issue of Developmental Cell, Amulic et al. (2017) show that the terminally differentiated, non-cycling neutrophils repurpose cell-cycle proteins and pathways to form NETs.


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Channel Nucleoporins Recruit PLK-1 to Nuclear Pore Complexes to Direct Nuclear Envelope Breakdown in C. elegans

Publication date: 23 October 2017
Source:Developmental Cell, Volume 43, Issue 2
Author(s): Lisa Martino, Stéphanie Morchoisne-Bolhy, Dhanya K. Cheerambathur, Lucie Van Hove, Julien Dumont, Nicolas Joly, Arshad Desai, Valérie Doye, Lionel Pintard
In animal cells, nuclear envelope breakdown (NEBD) is required for proper chromosome segregation. Whereas mitotic kinases have been implicated in NEBD, how they coordinate their activity to trigger this event is unclear. Here, we show that both in human cells and Caenorhabditis elegans, the Polo-like kinase 1 (PLK-1) is recruited to the nuclear pore complexes, just prior to NEBD, through its Polo-box domain (PBD). We provide evidence that PLK-1 localization to the nuclear envelope (NE) is required for efficient NEBD. We identify the central channel nucleoporins NPP-1/Nup58, NPP-4/Nup54, and NPP-11/Nup62 as the critical factors anchoring PLK-1 to the NE in C. elegans. In particular, NPP-1, NPP-4, and NPP-11 primed at multiple Polo-docking sites by Cdk1 and PLK-1 itself physically interact with the PLK-1 PBD. We conclude that nucleoporins play an unanticipated regulatory role in NEBD, by recruiting PLK-1 to the NE thereby facilitating phosphorylation of critical downstream targets.

Graphical abstract

Teaser

Nuclear envelope breakdown (NEBD) is required for proper chromosome segregation in animal cells. Martino et al. show that the Polo-like kinase Plk1 is required for efficient NEBD in both C. elegans and human cells and is recruited to the nuclear envelope by the central channel nucleoporins.


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Versatile Scaffold: Extrajunctional Roles for α-Catenin

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4
Author(s): Srikanth Budnar, Alpha S. Yap
α-catenin is a scaffolding molecule that can bind F-actin and other cytoskeletal proteins. It is best known for its contribution to cell-cell adhesion. In this issue of Developmental Cell, Vassilev et al. (2017) identify an extrajunctional pool of α-catenin that regulates RhoA signaling and controls directional migration of single cells.

Teaser

α-catenin is a scaffolding molecule that can bind F-actin and other cytoskeletal proteins. It is best known for its contribution to cell-cell adhesion. In this issue of Developmental Cell, Vassilev et al. (2017) identify an extrajunctional pool of α-catenin that regulates RhoA signaling and controls directional migration of single cells.


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ORP-Mediated ER Contact with Endocytic Sites Facilitates Actin Polymerization

Publication date: Available online 22 November 2017
Source:Developmental Cell
Author(s): Javier Encinar del Dedo, Fatima-Zahra Idrissi, Isabel María Fernandez-Golbano, Patricia Garcia, Elena Rebollo, Marek K. Krzyzanowski, Helga Grötsch, Maria Isabel Geli
Oxysterol binding protein-related proteins (ORPs) are conserved lipid binding polypeptides, enriched at ER contacts sites. ORPs promote non-vesicular lipid transport and work as lipid sensors in the context of many cellular tasks, but the determinants of their distinct localization and function are not understood. Here, we demonstrate that the yeast endocytic invaginations associate with the ER and that this association specifically requires the ORPs Osh2 and Osh3, which bridge the endocytic myosin-I Myo5 to the ER integral-membrane VAMP-associated protein (VAP) Scs2. Disruption of the ER contact with endocytic sites using ORP, VAP, myosin-I, or reticulon mutants delays and weakens actin polymerization and interferes with vesicle scission. Finally, we provide evidence suggesting that ORP-dependent sterol transfer facilitates actin polymerization at endocytic sites.

Graphical abstract

Teaser

Clathrin-mediated endocytosis from the plasma membrane is thought to mostly rely on the assembly of a coat built from cytosolic proteins. In contrast, Encinar et al. demonstrate that the ER contacts endocytic sites and plays a role in facilitating membrane invagination for endocytosis.


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Intestinal Flossing Keeps Pathogens at Bay

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4
Author(s): Mirela Kuka, Matteo Iannacone
Intraepithelial lymphocytes (IELs) are tissue-resident immune cells that surveil the intestine and provide the first line of defense against pathogens. Reporting in Cell, van Konijnenburg et al. (2017) combine high-resolution microscopy and intersectional genetic tools to provide a detailed characterization of IEL dynamics in response to both commensal and pathogenic microorganisms.

Teaser

Intraepithelial lymphocytes (IELs) are tissue-resident immune cells that surveil the intestine and provide the first line of defense against pathogens. Reporting in Cell, van Konijnenburg et al. (2017) combine high-resolution microscopy and intersectional genetic tools to provide a detailed characterization of IEL dynamics in response to both commensal and pathogenic microorganisms.


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ESRP1 Mutations Cause Hearing Loss due to Defects in Alternative Splicing that Disrupt Cochlear Development

Publication date: 6 November 2017
Source:Developmental Cell, Volume 43, Issue 3
Author(s): Alex M. Rohacek, Thomas W. Bebee, Richard K. Tilton, Caleb M. Radens, Chris McDermott-Roe, Natoya Peart, Maninder Kaur, Michael Zaykaner, Benjamin Cieply, Kiran Musunuru, Yoseph Barash, John A. Germiller, Ian D. Krantz, Russ P. Carstens, Douglas J. Epstein
Alternative splicing contributes to gene expression dynamics in many tissues, yet its role in auditory development remains unclear. We performed whole-exome sequencing in individuals with sensorineural hearing loss (SNHL) and identified pathogenic mutations in Epithelial Splicing-Regulatory Protein 1 (ESRP1). Patient-derived induced pluripotent stem cells showed alternative splicing defects that were restored upon repair of an ESRP1 mutant allele. To determine how ESRP1 mutations cause hearing loss, we evaluated Esrp1^−/− mouse embryos and uncovered alterations in cochlear morphogenesis, auditory hair cell differentiation, and cell fate specification. Transcriptome analysis revealed impaired expression and splicing of genes with essential roles in cochlea development and auditory function. Aberrant splicing of Fgfr2 blocked stria vascularis formation due to erroneous ligand usage, which was corrected by reducing Fgf9 gene dosage. These findings implicate mutations in ESRP1 as a cause of SNHL and demonstrate the complex interplay between alternative splicing, inner ear development, and auditory function.

Graphical abstract

Teaser

Rohacek et al. identify mutations in an alternative splice regulator, ESRP1, in a family with hearing loss. Loss of Esrp1 in mice leads to morphological defects in inner ear development and cell fate switches in the lateral cochlear wall caused by altered Fgfr2 splicing patterns and Fgf ligand usage.


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Mitosis sans Mitosis: The Mitotic Oscillator in Differentiation

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4
Author(s): Miranda Stratton, Tim Stearns
Differentiation and proliferation are usually considered to be antagonistic partners in development. However, in a recent issue of Science, Al Jord et al. (2017) show that key regulators of the mitotic cycle are redeployed in differentiating multiciliated cells to promote ciliogenesis without mitotic progression.

Teaser

Differentiation and proliferation are usually considered to be antagonistic partners in development. However, in a recent issue of Science, Al Jord et al. (2017) show that key regulators of the mitotic cycle are redeployed in differentiating multiciliated cells to promote ciliogenesis without mitotic progression.


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HBL1 Is a Human Long Noncoding RNA that Modulates Cardiomyocyte Development from Pluripotent Stem Cells by Counteracting MIR1

Publication date: 6 November 2017
Source:Developmental Cell, Volume 43, Issue 3
Author(s): Juli Liu, Yang Li, Bo Lin, Yi Sheng, Lei Yang




http://ift.tt/2zUCAqw

Skin and Its Regenerative Powers: An Alliance between Stem Cells and Their Niche

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4
Author(s): Kevin Andrew Uy Gonzales, Elaine Fuchs
Tissues have a natural capacity to replace dying cells and to heal wounds. This ability resides in resident stem cells, which self-renew, preserve, and repair their tissue during homeostasis and following injury. The skin epidermis and its appendages are subjected to daily assaults from the external environment. A high demand is placed on renewal and regeneration of the skin's barrier in order to protect the body from infection and dehydration and to heal wounds. This review focuses on the epithelial stem cells of skin, where they come from, where they reside, and how they function in normal homeostasis and wound repair.

Teaser

Epithelial stem cells help protect the body from infection and dehydration via renewal and regeneration of the skin. This review from Gonzales and Fuchs examines the biology of epithelial stem cells, where they come from, where they reside, and how they function in normal homeostasis and wound repair.


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The Plk1 Piece of the Nuclear Envelope Disassembly Puzzle

Publication date: 23 October 2017
Source:Developmental Cell, Volume 43, Issue 2
Author(s): T. Renee Dawson, Susan R. Wente
Reporting in this issue of Developmental Cell, Linder et al. (2017) and Martino et al. (2017) reveal in highly complementary studies that Plk1 is recruited to the nuclear pore complex upon mitotic entry, where it acts with Cdk1 to hyperphosphorylate nucleoporin interfaces to promote NPC disassembly and nuclear envelope breakdown.

Teaser

Reporting in this issue of Developmental Cell, Linder et al. (2017) and Martino et al. (2017) reveal in highly complementary studies that Plk1 is recruited to the nuclear pore complex upon mitotic entry, where it acts with Cdk1 to hyperphosphorylate nucleoporin interfaces to promote NPC disassembly and nuclear envelope breakdown.


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Cell Invasion In Vivo via Rapid Exocytosis of a Transient Lysosome-Derived Membrane Domain

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4
Author(s): Kaleb M. Naegeli, Eric Hastie, Aastha Garde, Zheng Wang, Daniel P. Keeley, Kacy L. Gordon, Ariel M. Pani, Laura C. Kelley, Meghan A. Morrissey, Qiuyi Chi, Bob Goldstein, David R. Sherwood
Invasive cells use small invadopodia to breach basement membrane (BM), a dense matrix that encases tissues. Following the breach, a large protrusion forms to clear a path for tissue entry by poorly understood mechanisms. Using RNAi screening for defects in Caenorhabditis elegans anchor cell (AC) invasion, we found that UNC-6(netrin)/UNC-40(DCC) signaling at the BM breach site directs exocytosis of lysosomes using the exocyst and SNARE SNAP-29 to form a large protrusion that invades vulval tissue. Live-cell imaging revealed that the protrusion is enriched in the matrix metalloprotease ZMP-1 and transiently expands AC volume by more than 20%, displacing surrounding BM and vulval epithelium. Photobleaching and genetic perturbations showed that the BM receptor dystroglycan forms a membrane diffusion barrier at the neck of the protrusion, which enables protrusion growth. Together these studies define a netrin-dependent pathway that builds an invasive protrusion, an isolated lysosome-derived membrane structure specialized to breach tissue barriers.

Graphical abstract

Teaser

How do invasive cells clear an entry path after basement membrane breach? Naegeli et al. show in Caenorhabditis elegans that directed lysosome exocytosis regulated by a netrin-mediated pathway builds the large invasive protrusion formed after invadopodia. Isolated by a dystroglycan membrane diffusion barrier, the protrusion expands to create tissue openings.


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The Origin of Animal Multicellularity and Cell Differentiation

Publication date: 23 October 2017
Source:Developmental Cell, Volume 43, Issue 2
Author(s): Thibaut Brunet, Nicole King
Over 600 million years ago, animals evolved from a unicellular or colonial organism whose cell(s) captured bacteria with a collar complex, a flagellum surrounded by a microvillar collar. Using principles from evolutionary cell biology, we reason that the transition to multicellularity required modification of pre-existing mechanisms for extracellular matrix synthesis and cytokinesis. We discuss two hypotheses for the origin of animal cell types: division of labor from ancient plurifunctional cells and conversion of temporally alternating phenotypes into spatially juxtaposed cell types. Mechanistic studies in diverse animals and their relatives promise to deepen our understanding of animal origins and cell biology.

Teaser

Brunet and King examine the origin of animal multicellularity. The authors suggest that changes in the mechanisms regulating extracellular matrix synthesis and cytokinesis may underlie the transition to multicellularity, and they propose two hypotheses to explain the evolution of cell differentiation in the animal lineage.


http://ift.tt/2ANqsIf

Tumor-Suppressor Inactivation of GDF11 Occurs by Precursor Sequestration in Triple-Negative Breast Cancer

Publication date: 20 November 2017
Source:Developmental Cell, Volume 43, Issue 4
Author(s): Sameer S. Bajikar, Chun-Chao Wang, Michael A. Borten, Elizabeth J. Pereira, Kristen A. Atkins, Kevin A. Janes
Triple-negative breast cancer (TNBC) is an aggressive and heterogeneous carcinoma in which various tumor-suppressor genes are lost by mutation, deletion, or silencing. Here we report a tumor-suppressive mode of action for growth-differentiation factor 11 (GDF11) and an unusual mechanism of its inactivation in TNBC. GDF11 promotes an epithelial, anti-invasive phenotype in 3D triple-negative cultures and intraductal xenografts by sustaining expression of E-cadherin and inhibitor of differentiation 2 (ID2). Surprisingly, clinical TNBCs retain the GDF11 locus and expression of the protein itself. GDF11 bioactivity is instead lost because of deficiencies in its convertase, proprotein convertase subtilisin/kexin type 5 (PCSK5), causing inactive GDF11 precursor to accumulate intracellularly. PCSK5 reconstitution mobilizes the latent TNBC reservoir of GDF11 in vitro and suppresses triple-negative mammary cancer metastasis to the lung of syngeneic hosts. Intracellular GDF11 retention adds to the concept of tumor-suppressor inactivation and reveals a cell-biological vulnerability for TNBCs lacking therapeutically actionable mutations.

Graphical abstract

Teaser

Tumor suppressors are frequently inactivated by mutation, deletion, or silencing of the encoding gene. Bajikar et al. identify a tumor-suppressive role for growth-differentiation factor 11 (GDF11) in triple-negative breast cancer and find GDF11 function is lost in this context through deficient protein maturation, causing intracellular accumulation of inactive pro-GDF11 precursor.


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Rapid non-genomic modulation by neurosteroids of dendritic spines in the hippocampus: androgen, estrogen and corticosteroid

Abstract

Memories are stored in synapses which consist of axon terminals and dendritic spines. Dendritic spines are postsynaptic structures of synapses and essential for synaptic plasticity and cognition. Therefore, extensive investigations about functions and structures of spines have been performed. Sex steroids and stress steroids have been shown to modulate hippocampal synapses.

Although rapid modulatory action of sex steroids on synapses has been studied in hippocampal neurons over several decades, its essential molecular mechanisms have not been fully understood. We here describe kinase-dependent signaling mechanisms which can well explain the rapid non-genomic modulation of dendritic spinogenesis in rat and mouse hippocampal slices by application of sex steroids, including dihydrotestosterone (DHT), testosterone (T), estradiol (E2) and progesterone (PROG). We also indicate the role of synaptic (classic) sex steroid receptors which trigger these rapid synaptic modulations. Moreover, we describe rapid non-genomic spine modulation by applying corticosterone (CORT), which is an acute stress model of the hippocampus.

The explanations of results are mainly based on the results from optical imaging of dendritic spines, and comparisons are also performed with results obtained from other types of imaging, including electron microscopic imaging. Relationships between spine modulation and modulation of cognition are discussed.

We can realize that most of rapid effects of exogenously applied estrogen and androgen were observed in steroid-depleted conditions, including acute slices of the hippocampus, castrated male animals and ovariectomized female animals. Therefore, the previously observed effects can be recognized as a kind of recovery events which may be essentially similar to hormone replacement therapy in hormone-declined condition. On the other hand in gonadally intact young animals with high level of endogenous sex hormones, further supplementation of sex hormones might not be effective, but rather infusion of blockers for steroid receptors or kinases may be effective to suppress sex hormone functions, leading to find useful information regarding molecular mechanisms.

This article is protected by copyright. All rights reserved.

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Repositioning the inframammary fold after DIEP flap reconstruction: using biologic mesh to provide a more stable result

Abstract

Traditional techniques for elevating the inframammary fold (IMF) position have relied mainly on isolated sutures to maintain the repositioned fold. Furthermore, most published reports focus on implant-based reconstructions, rather than the unique challenges of revising autologous reconstruction. Therefore, to improve the durability of the IMF repair in the autologous reconstructed breast, we have developed a method which utilizes biologic mesh to distribute the forces over a greater area of the chest wall. In our initial experience using this technique to elevate the IMF during revisions of autologous tissue breast reconstructions, we have found it to provide a stable and long-lasting result that can improve symmetry when the IMF position is not ideal.

http://ift.tt/2ixR4p1

Depressive Symptoms among Plastic Surgery Residents

Background: A literature review did not reveal any study investigating the prevalence of depression among plastic surgery residents. Methods: We conducted a cross-sectional mail survey and included all Saudi Plastic Surgery residents in our local program in Saudi Arabia. The Beck Depression Inventory II was used. Results: The inventory showed that mild, moderate, and severe depressive symptoms were prevalent in 20.6%, 38.2%, and 11.8%, respectively. Junior residents were more prone to depression. Conclusions: The high prevalence rate of depression among plastic surgery residents is alarming, and further studies are warranted. The problem has received no attention in the plastic surgery literature.

http://ift.tt/2j8Mw5F

Synthesis of Co 3 O 4 -Bi 2 O 3 using microwave-assisted method as the peroxymonosulfate activator for elimination of bisphenol A

Abstract

In this work, Co₃O₄-Bi₂O₃ was successfully synthesized using a microwave-assisted method [Co₃O₄-Bi₂O₃(MW)] and employed as a peroxymonosulfate (PMS) activator for bisphenol A removal. A reference catalyst was prepared using the same preparation conditions but different heating mode and labeled as Co₃O₄-Bi₂O₃(CH). The series of Co₃O₄-Bi₂O₃ was characterized using XRD, SEM, and N₂ adsorption to detect their crystallinity, morphology, and surface area, among others. Results indicated that both microwave and calcination significantly affected the characteristic and catalytic activity of the catalyst. Moreover, the microwave-irradiated catalyst calcined at 300 °C showed higher catalytic activity and mineralization percentage for BPA degradation than the conventionally heated catalyst calcined at the same temperature. Microwave temperature and microwave time of the proposed microwave-assisted method were also investigated. Compared with other catalysts, the present catalyst showed considerably superior preparation time and degradation efficiency. This study broadens a new horizon for advanced oxidation process using a PMS activator.

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Comment on “Effects of the GaAlAs diode laser (780 nm) on the periodontal tissues during orthodontic tooth movement in diabetes rats: histomorphological and immunohistochemical analysis”

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Chondroitin sulfate and glucosamine sulfate associated to photobiomodulation prevents degenerative morphological changes in an experimental model of osteoarthritis in rats

Abstract

The aim of this study was to compare the effects of combined treatment with chondroitin sulfate and glucosamine sulfate (CS/Gl) and photobiomodulation (PBM) on the degenerative process related to osteoarthritis (OA) in the articular cartilage in rats. Forty male Wistar rats were randomly divided into four groups: OA control group (CG); OA animals submitted to PBM treatment (PBM); OA animals submitted to CS/Gl treatment (CS/Gl); OA submitted to CS/GS associated with PBM treatments (GS/Gl + PBM). The CS/Gl started 48 h after the surgery, and they were performed for 29 consecutive days. Moreover, PBM was performed after the CS/Gl administration on the left joint. Morphological characteristics and immunoexpression of interleukin 10 (IL-10) and 1 beta (IL-1β) and collagen type II (Col II) of the articular cartilage were evaluated. The results showed that all treated groups (CS/Gl and PBM) presented attenuation signs of degenerative process (measured by histopathological analysis) and lower density chondrocytes [PBM (p = 0.0017); CS/Gl (p = 0.0153) and CS/Gl + PBM (p = 0.002)]. Additionally, CS/Gl [associated (p = 0.0089) or not with PBM (p = 0.0059)] showed significative lower values for OARSI grade evaluation. Furthermore, CS/GS + PBM decreased IL-1β protein expression (p = 0.0359) and increased IL-10 (p = 0.028) and Col II imunoexpression (p = 0.0204) compared to CG. This study showed that CS/Gl associated with PBM was effective in modulating inflammatory process and preventing the articular tissue degradation in the knees OA rats.

http://ift.tt/2zUkC7y

Laser for bone healing after oral surgery: systematic review

Abstract

The purpose of this study is to perform a systematic review on the use of lasers in oral surgery for bone healing. Selection of articles was carried out by two evaluators in Pubmed and Web of Science databases for published articles and OpenGray for gray literature. Search strategy was developed based on the PICO Question "Does the use of lasers after oral surgery improve bone healing?". Eligibility criteria were: being on laser; evaluate bone healing; involve oral surgery; do not be about implant, periodontics, orthodontics, osteonecrosis or radiotherapy, nor revisions, clinical cases, etc. Data were collected from each article in a structured spreadsheet and a descriptive analysis was performed. Risk assessment of bias of the articles was carried out through the tool elaborated by the Cochrane collaboration. A total of 827 potentially relevant references were identified. No articles were found in OpenGray. Eleven articles met the eligibility criteria and were included in the systematic review. Most of studies were in vivo and in jaw, being conducted with low-power lasers which were applied immediately after the surgical procedure of extraction. Neoformation and bone density were the outcomes of choice and there was a tendency of increase in bone density, neoformation, regeneration, mineralization, or bone condensation when laser was applied. Regarding the bias risk assessment, studies were not clear in reporting most of the parameters. Low-power laser therapy seems to reduce time of bone healing in oral surgery, although there are no defined protocols and the level of evidence is still considered weak.

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Scholar : Pediatric Hematology and Oncology, Volume 34, Issue 4, May 2017 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Pediatric Hematology and Oncology, Volume 34, Issue 4, May 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Leukemia, Lymphoma and Histiocytoses Combination of clofarabine, cyclophosphamide, and etoposide for relapsed or refractory childhood and adolescent acute myeloid leukemia Yoav Messinger, Jessica Boklan, John Goldberg, Steven G. DuBois, Javier Oesterheld, Oussama Abla, Alissa Martin, Joanna Weinstein & Nobuko Hijiya Pages: 187-198 | DOI: 10.1080/08880018.2017.1360970 Outcome of acute lymphoblastic leukemia in children with down syndrome—Polish pediatric leukemia and lymphoma study group report Joanna Zawitkowska PhD, Teresa Odój PhD, Katarzyna Drabko PhD, Agnieszka Zaucha-Prażmo PhD, Julia Rudnicka MD, Michał Romiszewski PhD, Michał Matysiak, Kinga Kwiecińska PhD, Magdalena Ćwiklińska PhD, Walentyna Balwierz, Joanna Owoc-Lempach PhD, Katarzyna Derwich PhD, Jacek Wachowiak, Maciej Niedźwiecki PhD, Elżbieta Adamkiewicz- Drożyńska, Joanna Trelińska PhD, Wojciech Młynarski, Andrzej Kołtan PhD, Mariusz Wysocki, Renata Tomaszewska PhD, Tomasz Szczepański, Marcin Płonowski PhD, Maryna Krawczuk-Rybak, Tomasz Ociepa PhD, Tomasz Urasiński, Agnieszka Mizia-Malarz PhD, Grażyna Sobol-Milejska PhD, Grażyna Karolczyk PhD & Jerzy Kowalczyk Pages: 199-205 | DOI: 10.1080/08880018.2017.1363837 Treatment of tumor lysis syndrome in children with leukemia/lymphoma in resource-limited settings—Efficacy of a fixed low-dose rasburicase K. G. Gopakumar MD, DNB, Priyakumari Thankamony MD, Ph.D., Shwetha Seetharam MD & Kusumakumary P MD Pages: 206-211 | DOI: 10.1080/08880018.2017.1348415 Solid Tumors and Neurooncology Analysis of clinical features of lipoblastoma in children Ji-Won Han MD, Hongbeom Kim MD, Joong Kee Youn MD, Chaeyoun Oh MD, Sung-Eun Jung MD, PhD, Kwi-Won Park MD, PhD, Seong-Cheol Lee MD, PhD & Hyun-Young Kim MD, PhD Pages: 212-220 | DOI: 10.1080/08880018.2017.1354949 FAK-Src-paxillin system expression and disease outcome in human neuroblastoma Panagiotis Kratimenos, Ioannis Koutroulis, Vasiliki Syriopoulou, Christina Michailidi, Maria Delivoria-Papadopoulos, Jerzy Klijanienko & Stamatios Theocharis Pages: 221-230 | DOI: 10.1080/08880018.2017.1360969 Pediatric NUT-midline carcinoma: Therapeutic success employing a sarcoma based multimodal approach Simone Storck MD, Alyssa L. Kennedy MD, PhD, Karen J. Marcus MD, Lisa Teot MD, Jennifer Vaughn MD, Astrid K. Gnekow MD, Bruno Märkl MD, Ivo Leuschner MD, Steven G. DuBois MD, Christopher A. French MD & Michael C. Frühwald MD, PhD Pages: 231-237 | DOI: 10.1080/08880018.2017.1363839 The prognostic importance of TGF-β, TGF-β receptor, and fascin in childhood solid tumors Hikmet Gulsah Tanyildiz, Gulsah Kaygusuz, Emel Unal, Nurdan Tacyildiz, Handan Dincaslan & Gulsan Yavuz Pages: 238-253 | DOI: 10.1080/08880018.2017.1363838 Dramatic clinical and radiographic response to BRAF inhibition in a patient with progressive disseminated optic pathway glioma refractory to MEK inhibition Abhishek Bavle, Jeremy Jones, Frank Y. Lin, Amy Malphrus, Adekunle Adesina & Jack Su Pages: 254-259 | DOI: 10.1080/08880018.2017.1360971 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : These new articles for The Law Teacher are available online

The online platform for Taylor & Francis Online content New for The Law Teacher and online now on Taylor & Francis Online: Original Articles Changes to the training of English and Welsh lawyers: implications for the future of university law schools Mark Davies Pages: 1-26 | DOI: 10.1080/03069400.2017.1394145 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Activities, Adaptation & Aging, Volume 41, Issue 4, October-December 2017 is now available online on Taylor & Francis Online

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The online platform for Taylor & Francis Online content Activities, Adaptation & Aging, Volume 41, Issue 4, October-December 2017 is now available online on Taylor & Francis Online. This new issue contains the following articles: Original Articles Leisure, Relatedness, and Ill-Being among Older Adults in Long-Term Care James M. Duncan, Timothy S. Killian & Mallory Lucier-Greer Pages: 273-290 | DOI: 10.1080/01924788.2017.1326764 Evaluation of Rewind Yoga on Physical Function Outcomes in Older Adults: A Preliminary Study Andrew I. Miller, Cheryl Der Ananian, Carrie Hensley & Heidi Ungar Pages: 291-300 | DOI: 10.1080/01924788.2017.1326765 Loneliness in Old Age: Interventions to Curb Loneliness in Long-Term Care Facilities Rachel E. Brimelow & Judy A. Wollin Pages: 301-315 | DOI: 10.1080/01924788.2017.1326766 Video Conferencing: An Intervention for Emotional Loneliness in Long-Term Care Mary T. Siniscarco, Cynthia Love-Williams & Sarah Burnett-Wolle Pages: 316-329 | DOI: 10.1080/01924788.2017.1326763 Engagement of Residents of Assisted Living and Skilled Nursing Facility Memory Care Units Katie Westberg, Phyllis M. Gaspar & Constance Schein Pages: 330-346 | DOI: 10.1080/01924788.2017.1376175 Book Review Razz Ma Tazz: My Life in Music, Television and Film by Stan Zabka Big Island Music, 2013, 223 pages, softcover, $12.98 Debra Rose Wilson & William Wilson Pages: 347-348 | DOI: 10.1080/01924788.2017.1391572 Editorial Board Editorial Board EOV Pages: 349-349 | DOI: 10.1080/01924788.2017.1400808 2018 Future Directions Forum JOIN US at the 2018 Future Directions Forum for Journal of Clinical Child & Adolescent Psychology - June 15-16, 2018 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Joint toxicity of six common heavy metals to Chlorella pyrenoidosa

Abstract

Six common heavy metals (Ni, Fe, Zn, Pb, Cd, and Cr) in the water environment were selected to present five groups of binary mixture systems (Ni-Fe, Ni-Zn, Ni-Pb, Ni-Cd, and Ni-Cr) through a direct equipartition ray design. Microplate toxicity analysis based on Chlorella pyrenoidosa measured the 96-h joint toxicities of the binary mixtures. Toxicity interaction of the binary mixture was analyzed by comparing the observed toxicity data with the reference model (concentration addition). The results indicated that Ni-Fe, Ni-Pb, and Ni-Cr mixtures showed additive effects at concentration tested. It was indicated that Ni-Zn and Ni-Cd mixtures presented additive effects at low concentrations whereas synergistic effects were seen at high concentrations.

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Scholar : These new articles for Applied Developmental Science are available online

The online platform for Taylor & Francis Online content New for Applied Developmental Science and online now on Taylor & Francis Online: Original Articles Teachers' civic socialization practices and children's civic engagement Elizabeth S. White & Rashmita S. Mistry Pages: 1-20 | DOI: 10.1080/10888691.2017.1377078 Role of school climate and personality in the development of Czech adolescents' political self-efficacy Jan Šerek & Hana Machackova Pages: 1-11 | DOI: 10.1080/10888691.2017.1364163 2018 Future Directions Forum JOIN US at the 2018 Future Directions Forum for Journal of Clinical Child & Adolescent Psychology - June 15-16, 2018 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Scholar : Critical Discourse Studies, Volume 15, Issue 1, February 2018 is now available online on Taylor & Francis Online

The online platform for Taylor & Francis Online content Critical Discourse Studies, Volume 15, Issue 1, February 2018 is now available online on Taylor & Francis Online. This new issue contains the following articles: Original Articles Logics, assumptions and genre chains: a framework for poststructuralist policy analysis Elise Remling Pages: 1-18 | DOI: 10.1080/17405904.2017.1382382 Memory, media, and museum audience's discourse of remembering Chaim Noy Pages: 19-38 | DOI: 10.1080/17405904.2017.1392331 Multimodal strategies of emotional governance: a critical analysis of 'nudge' tactics in health policy Jane Mulderrig Pages: 39-67 | DOI: 10.1080/17405904.2017.1382381 Canada the redeemer and denials of racism Trevor Gulliver Pages: 68-86 | DOI: 10.1080/17405904.2017.1360192 'If you look at me like at a piece of meat, then that's a problem' – women in the center of the male gaze. Feminist Poststructuralist Discourse Analysis as a tool of critique Ewa Glapka Pages: 87-103 | DOI: 10.1080/17405904.2017.1390480 BOOK REVIEW Poststructural policy analysis – a guide to practice Oscar Larsson Pages: 104-106 | DOI: 10.1080/17405904.2017.1342679 Corrigenda Corrigendum Pages: (i)-(i) | DOI: 10.1080/17405904.2017.1397348 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Issue Information

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Scholar : These new articles for Asian Security are available online

The online platform for Taylor & Francis Online content New for Asian Security and online now on Taylor & Francis Online: Original Articles Downsizing Hegemony: Alliance, Domestic Politics, and American Retrenchment in East Asia, 1969–2017 Il Hyun Cho Pages: 1-17 | DOI: 10.1080/14799855.2017.1403900 Interested in the political-economic topics surrounding China? You wouldn't want to miss this exclusive collection. To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Film-forming ability of collagen hydrolysate extracted from leather solid wastes with chitosan

Abstract

Discharges of huge quantities of leather solid wastes by leather industries and the increased use of synthetic packaging films have raised serious concerns on account of their environmental impacts. The paper focuses on the development and characterization of potential environmentally friendly composite films using collagen hydrolysate (CH) extracted from leather solid wastes and chitosan (C) to assess the feasibility of producing polymeric materials suitable for applications in packaging and wrapping purposes. Solid collagen-based protein hydrolysate was extracted from chromium-tanned leather wastes and analyzed to determine its chemical properties. With the goal of improving the physico-chemical performance of CH, three types of composite films (CH75/C25, CH50/C50, CH25/C75) were prepared with increasing concentrations of C, and some of their physical and functional properties were characterized. The results indicated that the addition of C caused increase (p < 0.05) in the thickness, tensile strength (TS), elasticity modulus (EM), and water vapor permeability (WVP), leading to stronger films as compared with CH film, but significantly (p < 0.05) decreased the elongation at break (EAB) and solubility of films (p < 0.05). The light barrier measurements present low values of transparency at 600 nm of the CH/C films, indicating that the films are very transparent and they have excellent barrier properties against UV light. The structural properties investigated by FTIR and DSC showed total miscibility between both polymers. Scanning electron micrographs revealed that CH/C composite films showed a compact homogeneous structure. These results demonstrate the potential application of CH/C composite films in packaging industry.

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The physics of small megavoltage photon beam dosimetry

Publication date: Available online 30 November 2017
Source:Radiotherapy and Oncology
Author(s): Pedro Andreo
The increased interest during recent years in the use of small megavoltage photon beams in advanced radiotherapy techniques has led to the development of dosimetry recommendations by different national and international organizations. Their requirement of data suitable for the different clinical options available, regarding treatment units and dosimetry equipment, has generated a considerable amount of research by the scientific community during the last decade. The multiple publications in the field have led not only to the availability of new invaluable data, but have also contributed substantially to an improved understanding of the physics of their dosimetry. This work provides an overview of the most important aspects that govern the physics of small megavoltage photon beam dosimetry.



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Editorial Board & Aims and Scope

Publication date: December 2017
Source:Nano Today, Volume 17





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Editorial Board

Publication date: January 2018
Source:Medical Image Analysis, Volume 43





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Neurons in the Human Left Amygdala Automatically Encode Subjective Value Irrespective of Task

Abstract

The amygdala plays an important role in the computation of internal reward signals. In animals it has been shown to enable a stimulus to indicate the current value of a reinforcer. However, the exact nature of the current value representations in humans remains unknown. Specifically, do neurons of the human amygdala represent current value signals only in tasks requiring valuation? We recorded from 406 neurons in the amygdala, orbitofrontal cortex, parahippocampal cortex, entorhinal cortex, and hippocampus of 6 neurosurgical patients while subjects repeatedly viewed 40 different pictures of sweet or salty "junk food" items in 2 different tasks. Neural activity during stimulus inspection in a valuation task reflected food preferences in the amygdala, orbitofrontal cortex, hippocampus, and entorhinal cortex. Notably, only left amygdala activity represented these food preferences even in a sweet–salty classification task. Valuation signals of the left amygdala thus appear to be stimulus-, not-task driven.

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Distal Functional Connectivity of Known and Emerging Cortical Targets for Therapeutic Noninvasive Stimulation

Abstract

Noninvasive stimulation is an emerging modality for the treatment of psychiatric disorders, including addiction. A crucial element in effective cortical target selection is its distal influence. We approached this question by examining resting-state functional connectivity patterns in known and potential stimulation targets in 145 healthy adults. We compared connectivity patterns with distant regions of particular relevance in the development and maintenance of addiction. We used stringent Bonferroni-correction for multiple comparisons. We show how the anterior insula, dorsal anterior cingulate, and ventromedial prefrontal cortex had opposing functional connectivity with striatum compared to the dorsomedial prefrontal cortex. However, the dorsolateral prefrontal cortex, the currently preferred target, and the presupplementary motor area had strongest negative connections to amygdala and hippocampus. Our findings highlight differential and opposing influences as a function of cortical site, underscoring the relevance of careful cortical target selection dependent on the desired effect on subcortical structures. We show the relevance of dorsal anterior cingulate and ventromedial prefrontal cortex as emerging cortical targets, and further emphasize the anterior insula as a potential promising target in addiction treatment, given its strong connections to ventral striatum, putamen, and substantia nigra.

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Mechanical properties optimization of AZX612-Mg alloy joint by double-sided friction stir welding

Publication date: April 2018
Source:Journal of Materials Processing Technology, Volume 254
Author(s): Mengran Zhou, Yoshiaki Morisada, Hidetoshi Fujii, Takeshi Ishikawa
AZX612 (Mg-6% Al-1% Zn-2% Ca) non-combustive magnesium alloy joints formed by asymmetric double-sided friction stir welding with different lower tool rotation rates were investigated. Compared with the conventional one-sided friction stir welding, joints fabricated by the asymmetric double-sided friction stir welding showed better tensile strength and elongation values. EBSD observations of the stir zone indicate that the stir zone formed at the upper and lower tool rotation rates of 600rpm and 500rpm exhibits the lowest 〈0001〉 texture intensity thereby showing the best balance of tensile strength and ductility. With defect-free joining parameters, the complexity of the material flow caused by the asymmetric layout of the double tools needs both a small difference between the upper and lower tool rotation rates and a proper heat input.

Graphical abstract

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Metastatic serous carcinoma presenting as inflammatory carcinoma over the breast – report of two cases and literature review

Abstract

Non-mammary metastases involving breast are rare and most commonly involve the breast parenchyma. Infrequently, metastasis from an extramammary primary site presents as inflammatory carcinoma over the breast. Diagnosis of such lesions can be challenging, especially in patients with co-existing primary breast carcinoma. Few such cases have been described in literature; however, none of the previously reported cases had a prior history of primary breast carcinoma.

We present two patients with history of breast carcinoma and serous carcinoma of ovarian/peritoneal origin that presented with inflammatory carcinoma over the breast. Biopsies from breast tissue showed atypical cells in the dermis forming cords and papillary structures. Histopathologic differential diagnosis included infiltrating ductal carcinoma of breast origin and metastatic serous carcinoma. Immunohistochemical studies showed that the tumor cells were positive for markers of ovarian origin such as PAX-8 and CA125 and negative for breast markers such as GATA-3, thus supporting the diagnosis.

In summary, we describe the unusual presentation of metastatic serous carcinoma as inflammatory carcinoma over breast and discuss the diagnostic challenges in patients with co-existing primary breast and ovarian malignancies. We also review the morphologic features of tumors of breast and ovarian origin and the immunohistochemical stains to differentiate these two entities.

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Metastatic Laryngeal Large Cell Neuroendocrine Carcinoma: A Rare Case of Presentation and Extreme Tumor Burden

ABSTRACT

Large cell neuroendocrine carcinoma (LCNEC) of the larynx is an aggressive form of neuroendocrine carcinoma that affects smokers at an average age of 60 years. LCNEC is characterized by large cells with round to ovoid nuclei distributed in a trabecular or nested growth pattern. Previously, laryngeal LCNEC and atypical carcinoid tumors were considered synonymous; however, laryngeal LCNEC has been shown to have higher mitotic rates and worse prognosis, which has led to laryngeal LCNEC to be separated from atypical carcinoid and classified as a poorly differentiated neuroendocrine carcinoma in the most recent World Health Organization classification. We present a case of a 56-year-old female who presented with painful subcutaneous skin lesions that were diagnosed as metastatic carcinoma at an outside facility. Subsequent workup revealed a primary epiglottic lesion. Over the next 4 years, she continued to develop over 100 similar subcutaneous nodules. Additional workup confirmed neuroendocrine differentiation, thus clarifying the diagnosis of metastatic large cell neuroendocrine carcinoma. Review of literature has only revealed one reported case of LCNEC with skin metastasis. This is the first reported case whereby skin metastasis was the initial presenting symptom; moreover, our case is unique with regard to the heavy metastatic burden to the skin.

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Glut3 Addiction Is a Druggable Vulnerability for a Molecularly Defined Subpopulation of Glioblastoma

Publication date: Available online 30 November 2017
Source:Cancer Cell
Author(s): Érika Cosset, Sten Ilmjärv, Valérie Dutoit, Kathryn Elliott, Tami von Schalscha, Maria F. Camargo, Alexander Reiss, Toshiro Moroishi, Laetitia Seguin, German Gomez, Jung-Soon Moo, Olivier Preynat-Seauve, Karl-Heinz Krause, Hervé Chneiweiss, Jann N. Sarkaria, Kun-Liang Guan, Pierre-Yves Dietrich, Sara M. Weis, Paul S. Mischel, David A. Cheresh
While molecular subtypes of glioblastoma (GBM) are defined using gene expression and mutation profiles, we identify a unique subpopulation based on addiction to the high-affinity glucose transporter, Glut3. Although Glut3 is a known driver of a cancer stem cell phenotype, direct targeting is complicated by its expression in neurons. Using established GBM lines and patient-derived stem cells, we identify a subset of tumors within the "proneural" and "classical" subtypes that are addicted to aberrant signaling from integrin αvβ3, which activates a PAK4-YAP/TAZ signaling axis to enhance Glut3 expression. This defined subpopulation of GBM is highly sensitive to agents that disrupt this pathway, including the integrin antagonist cilengitide, providing a targeted therapeutic strategy for this unique subset of GBM tumors.

Graphical abstract

Teaser

Cosset et al. identify a subset of glioblastoma within the proneural and the classical subtypes that are addicted to aberrant signaling from integrin αvβ3, which activates a PAK4-YAP/TAZ signaling axis to enhance Glut3 expression, and are sensitive to agents disrupting the pathway such as cilengitide.


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Antibody Tumor Targeting Is Enhanced by CD27 Agonists through Myeloid Recruitment

Publication date: Available online 30 November 2017
Source:Cancer Cell
Author(s): Anna H. Turaj, Khiyam Hussain, Kerry L. Cox, Matthew J.J. Rose-Zerilli, James Testa, Lekh N. Dahal, H.T. Claude Chan, Sonya James, Vikki L. Field, Matthew J. Carter, Hyung J. Kim, Jonathan J. West, Lawrence J. Thomas, Li-Zhen He, Tibor Keler, Peter W.M. Johnson, Aymen Al-Shamkhani, Stephen M. Thirdborough, Stephen A. Beers, Mark S. Cragg, Martin J. Glennie, Sean H. Lim
Monoclonal antibodies (mAbs) can destroy tumors by recruiting effectors such as myeloid cells, or targeting immunomodulatory receptors to promote cytotoxic T cell responses. Here, we examined the therapeutic potential of combining a direct tumor-targeting mAb, anti-CD20, with an extended panel of immunomodulatory mAbs. Only the anti-CD27/CD20 combination provided cures. This was apparent in multiple lymphoma models, including huCD27 transgenic mice using the anti-huCD27, varlilumab. Detailed mechanistic analysis using single-cell RNA sequencing demonstrated that anti-CD27 stimulated CD8⁺ T and natural killer cells to release myeloid chemo-attractants and interferon gamma, to elicit myeloid infiltration and macrophage activation. This study demonstrates the therapeutic advantage of using an immunomodulatory mAb to regulate lymphoid cells, which then recruit and activate myeloid cells for enhanced killing of mAb-opsonized tumors.

Graphical abstract

Teaser

Turaj et al. test anti-tumor efficacy of immunomodulatory antibodies combined with anti-CD20 and find that anti-CD27/CD20 has a strong benefit in several tumor models. Anti-CD27 induces IFNγ and chemokines in CD8⁺ T and NK cells, enhancing macrophage infiltration and activation to promote anti-CD20 activity.


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Breast Involvement by Hematologic Malignancies: Ultrasound and Elastography Findings with Clinical Outcomes

Hulya Aslan, Aysin Pourbagher

Journal of Clinical Imaging Science 2017 7(1):42-42

Objective: Hematological malignancies very rarely involve the breast. The aim of this study is to retrospectively evaluate B-mode ultrasound (US) and elastography (ES) findings of breast involvement by hematologic malignancies with clinical outcomes. Materials and Methods: All core-needle biopsy results that were performed at our tertiary breast center from January 2013 to September 2016 were searched. Our search revealed 9 patients with breast involvement either by leukemia or lymphoma. All patients were examined using B-mode US and ES. US and ES findings were analyzed with the consensus of two radiologists, and clinical outcomes were noted. Results: The mean age of the study population was 41.6 years (range, 20–83 years). Two patients showed diffuse hypoechoic parenchymal infiltration. The elasticity assessments of these lesions were soft and intermediate. The remaining 7 patients had mass lesions. The elasticity assessment of these masses according to Breast Imaging Reporting and Data System US was as follows: Soft (n = 1), intermediate (n = 4), high (n = 2). Conclusions: It is important to consider that hematologic malignancies may appear as soft or intermediate lesions on ES. Patients' history and clinical background should help us to consider breast involvement. In addition, the clinical outcomes may not be related with elasticity assessments.

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Letter to the Editor regarding the paper by F. Cardoso et al. ‘European Breast Cancer Conference manifesto on breast centres/units’

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Gianni Saguatti, Carlo Naldoni, Eva Benelli, Chiara Fedato, Alfonso Frigerio, Vania Galli, Livia Giordano, Paola Golinelli, Doralba Morrone, Adriana Paduos, Fiammetta Querci, Antonio Rizzo, Lauro Bucchi




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Immune checkpoint inhibitor–associated CNS autoimmune disorder (ICICAD) following nivolumab treatment: A new entity of drug-induced autoimmune encephalitis?

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Herwig Strik, Ursula Keber, Wasim Alhaj Hammoud, Jorge Riera-Knorrenschild, Barbara Carl, Richard Dodel, Axel Pagenstecher, Andreas Neubauer




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Re: Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Peter C. Albertsen




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Reply to letter from Suguatti et al.

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Luigi Cataliotti, Lorenza Marotti, Marc Beishon, Alberto Costa, Susan Knox, Emiel Rutgers, Fatima Cardoso




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Response to letter – Androgen deprivation therapy and cardiovascular risk: No meaningful difference between GnRH antagonist and agonists

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Lucie-Marie Scailteux




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European Research on Electrochemotherapy in Head and Neck Cancer (EURECA) project: Results from the treatment of mucosal cancers

Publication date: December 2017
Source:European Journal of Cancer, Volume 87
Author(s): Christina Caroline Plaschke, Giulia Bertino, James A. McCaul, Juan J. Grau, Remco de Bree, Gregor Sersa, Antonio Occhini, Ales Groselj, Cristobal Langdon, Derrek A. Heuveling, Maja Cemazar, Primoz Strojan, C. Rene Leemans, Marco Benazzo, Francesca De Terlizzi, Irene Wessel, Julie Gehl
AimElectrochemotherapy is an effective local treatment for cutaneous tumours and metastases. In this prospective trial, six European institutions investigated electrochemotherapy in recurrent, mucosal head and neck tumours.Patient and methodsForty-three patients with recurrent mucosal head and neck tumours and no further curative or reasonably effective palliative treatment options were enrolled and treated with electrochemotherapy. Patients were treated in general anaesthesia using intravenous or local injection of bleomycin followed by delivery of electric pulses to the tumour area. Primary end-point was local tumour response. Secondary end-points were safety and toxicity, overall and progression free survival, and quality-of-life.ResultsThirty-seven patients were evaluable for tumour response, pain score, side-effects and quality of life questionnaires. Six patients were not evaluable due to lost follow-up, disease progression or death before evaluation. Intention to treat analysis revealed an objective response of 56% (complete response 8 (19%), partial response 16 (37%), stable disease 10 (23%), progressive disease 3 (7%), and not evaluable 6 (14%)). Three patients (7%) remained in complete response at 30, 34, and 84 months post-treatment. The treatment procedure was generally well tolerated. Swelling of the mucosa was observed in the first days after treatment. Pain and use of pain medication rose temporarily; fatigue and dysphagia were also noted in the quality of life assessment.ConclusionElectrochemotherapy can be applied to mucosal head and neck recurrent tumours accessible to the procedure with promising objective response, survival and toxicity profile. Attention should be paid to post-treatment swelling and planning of pain medication. These favourable results indicate that electrochemotherapy could play a role in patients with recurrent head and neck cancer.



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The new Pan-American Neuroendocrine Society

Abstract

The new Pan-American Neuroendocrine Society already has an official journal, which of course is the Journal of Neuroendocrinology (JNE). This journal has been the primary presenter of the remarkable expansion of this field since 1989 – documenting its long history and ongoing development. The word Neuro-Endocrinologie, with the hyphen, first appeared in French in 1946 as the title of the enormous (1086 pages) book by Roussy and Mosinger (1).

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Characterization of CD45RO+ Memory T Lymphocytes in Keloid Disease

Abstract

Background

Memory T cells, a highly effective subset of T lymphocytes, have been reported to be involved in many inflammatory skin disorders. However, the potential role of memory T cells in keloid disease (KD) remains unclear.

Objectives

Due to their important role in regulating inflammation, we investigated the characteristics of CD45RO⁺ memory T cells (mT) in KD.

Methods

Primary cutaneous cells were isolated from keloid scars and normal skin by enzymic digestion. Combined with peripheral blood mononuclear cells (PBMCs) isolated from a related blood sample, flow cytometry was applied to identify the phenotypic and functional abnormalities of memory T cells in KD.

Results

We observed that the majority of T lymphocytes in keloid scars had the memory phenotype, and a greater number of the CD8⁺ mT in keloid scars produced lower levels of TNF-α. This abnormal cytokine production was even more distinct in FOXP3^-CD8^- mT, with lower TNF-α production and enhanced IFN-γ production. Furthermore, FOXP3⁺CD8^- mT in keloid scars were abnormal, including showing reduced CD25 and CTLA-4 expression and IL-10 production. In addition, a significant decrease in the number of CD4⁺CD25^highFOXP3⁺ regulatory T cells was identified in patients with multiple keloid scars. We also found that there was significantly increased infiltration of CD103⁺CD8⁺ mT in keloid scars.

Conclusions

Our findings preliminarily elucidate the abnormalities of CD45RO⁺ memory T cells in keloid scars and provide early evidence that a disrupted T cell response contributes to the progression of KD.

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Impaired Langerhans’ cell migration in psoriasis is due to an altered keratinocyte phenotype induced by interleukin-17

Abstract

Psoriasis is a common skin condition driven by increased expression of interleukin (IL)-17. Langerhans' cells (LC) are epidermal dendritic cells that regulate cutaneous immune responses. Within uninvolved skin of patients with psoriasis, LC display impaired migration from the epidermis. Here the role of keratinocytes (KC) in the regulation of LC function, and the response of KC to IL-17 has been investigated. Keratinocytes were cultured from the uninvolved skin of psoriasis patients and healthy individuals with or without IL-17 treatment and the conditioned medium examined for its ability to alter LC function in an ex vivo human skin explant model. Furthermore, we examined the effect of IL-17 on LC mobilisation in psoriasis by neutralising IL-17 in the same skin explant model. We found that conditioned medium from psoriasis KC inhibited LC migration in healthy skin. Moreover, conditioned medium from healthy KC treated with IL-17 also inhibited healthy LC migration. Finally, neutralising IL-17 in psoriasis skin resulted in enhanced LC migration. Collectively, these data suggest that an altered KC secretome, driven by increased expression of IL-17, is responsible for impaired LC migration in uninvolved skin of patients with psoriasis.

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Association of Burnout With Emotional Intelligence and Personality in Surgical Residents: Can We Predict Who Is Most at Risk?

Publication date: Available online 1 December 2017
Source:Journal of Surgical Education
Author(s): Brenessa Lindeman, Emil Petrusa, Sophia McKinley, Daniel A. Hashimoto, Denise Gee, Douglas S. Smink, John T. Mullen, Roy Phitayakorn
ObjectivesBurnout is common among surgical residents and may be related to personality characteristics, emotional intelligence (EI), or work experiences.DesignLongitudinal cohort study over 1 year.SettingTertiary academic medical centers in the Northeast.ParticipantsAll general surgery residents in 2 programs (n = 143) were invited to complete an electronic survey at 3 time points; 88, 64, and 69 residents completed the survey (overall response rate 52%).ResultsSevere burnout was observed in 51% of residents (n = 41). Higher scores were associated with female sex (p = 0.02). Burnout scores were highest at the beginning and end of the academic year; EI and personality scores remained stable. On bivariate analysis, high EI score (p < 0.001), agreeableness and emotional stability personality features (p = 0.003), and positive job experiences (p < 0.01) were protective against burnout. Higher EI and positive work experiences were independent predictors of lower burnout (p < 0.01) after multivariable adjustment.ConclusionsSurgical residents have high levels of burnout. Higher EI and positive work experiences are associated with lower burnout. Focused interventions to improve EI and optimize the work environment may prevent or lessen burnout.



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