Cell signalling articles within Nature Communications

Featured

• Article | 09 February 2015

  Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis

  Activation of the liver receptor CAR and β-catenin are both involved in hepatocellular carcinoma. Here, the authors show that combined activation of both CAR and β-catenin in mice can drive uncontrolled liver growth and is sufficient for hepatocarcinogenesis.

  • Bingning Dong
  • , Ju-Seog Lee
  •  & David D. Moore

• Article | 09 February 2015

  A leak pathway for luminal protons in endosomes drives oncogenic signalling in glioblastoma

  Glioblastoma multiforme is the most common and aggressive form of primary brain tumour, and in 50% of cases EFGR is mutated, amplified or upregulated. Here the authors show that NHE9 controls the amount of EGFR at the membrane surface of brain tumour-initiating stem cells by affecting the luminal pH of sorting endosomes.

  • Kalyan C. Kondapalli
  • , Jose P. Llongueras
  •  & Rajini Rao

• Article
  06 February 2015 | Open Access

  Ultrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets

  Antigenic peptides are loaded into major histocompatibility complex class I (MHC I) molecules after entering the ER via the TAP transporter. Here, Fischbach et al. develop a flow cytometry assay to monitor TAP-dependent peptide translocation that is sensitive enough to use on scarce primary cell subsets.

  • Hanna Fischbach
  • , Marius Döring
  •  & Robert Tampé

• Article | 05 February 2015

  Synthetic lateral inhibition governs cell-type bifurcation with robust ratios

  Cell-type diversity results from a series of binary cell fate decisions. Here, Matsuda et al.find that cells engineered with a Notch/Delta lateral inhibition circuit spontaneously bifurcate into Notch-active and Delta-positive subpopulations that are robust at the individual and population levels.

  • Mitsuhiro Matsuda
  • , Makito Koga
  •  & Miki Ebisuya

• Article | 05 February 2015

  Anoctamin 6 mediates effects essential for innate immunity downstream of P2X₇ receptors in macrophages

  Activation of purinergic P2X₇ receptors is important for phagocytosis and bacterial killing. Here the authors show that a phospholipid scramblase, Anoctamin 6, is activated downstream of P2X₇R and is a critical mediator of bacterial internalization and killing by macrophages.

  • Jiraporn Ousingsawat
  • , Podchanart Wanitchakool
  •  & Karl Kunzelmann

• Article | 05 February 2015

  MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and AMPK-dependent signalling in cancer

  Tumour cells sustain high levels of glycolysis even in presence of oxygen, which is known as the Warburg effect. Here the authors show that MnSOD contributes to the Warburg effect by increasing the levels of H₂O₂released from mitochondria, which sustains glycolysis by activating AMPK.

  • Peter C. Hart
  • , Mao Mao
  •  & Marcelo G. Bonini

• Article | 04 February 2015

  PYK2 sustains endosomal-derived receptor signalling and enhances epithelial-to-mesenchymal transition

  Proline-rich tyrosine kinase 2 (PYK2) has been previously involved in the positive regulation of epithelial-to-mesenchymal transition (EMT); however, the mechanisms were not known. Here the authors uncover key roles of PYK2 during EGF-induced EMT in human mammary cell lines involving STAT3 and c-MET.

  • Nandini Verma
  • , Omer Keinan
  •  & Sima Lev

• Article
  04 February 2015 | Open Access

  Collaborative rewiring of the pluripotency network by chromatin and signalling modulating pathways

  Improving the efficiency of reprogramming of somatic cells to induced pluripotent stem cells is of major interest. Here, the authors combine ascorbic acid and 2i (MAP kinase and GSK inhibitors) conditions and show increased efficiency and synchronicity in the reprogramming of fibroblasts and partially reprogrammed cells, and study epigenetic effectors and signalling pathways responsible for this effect.

  • Khoa A. Tran
  • , Steven A. Jackson
  •  & Rupa Sridharan

• Article
  03 February 2015 | Open Access

  Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor

  Microbial pathogens can activate both innate and adaptive receptors, and integration of these signals may enhance the sensitivity of the immune response. Freeman et al. show that innate microbial cues sensitize B cells to antigen by increasing actin dynamics and reducing the actin-dependent confinement of the B-cell receptor.

  • Spencer A. Freeman
  • , Valentin Jaumouillé
  •  & Michael R. Gold

• Article
  30 January 2015 | Open Access

  Endothelial destabilization by angiopoietin-2 via integrin β1 activation

  Angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) have opposing effects on vascular stability through their receptor Tie2, but there is evidence for Tie2-independent functions of Ang2. Here, Hakanpaa et al.show that Ang2 directly activates β1-integrin, leading to rearrangement of the actin cytoskeleton and decreased VE-cadherin in cell–cell junctions.

  • Laura Hakanpaa
  • , Tuomas Sipila
  •  & Pipsa Saharinen

• Article
  30 January 2015 | Open Access

  Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5

  Augmented AMP-activated protein kinase (AMPK) activity inhibits cell migration through an unknown mechanism. Here, Yan et al.show that AMPK phosphorylates the novel substrate PDZ and LIM domain 5 (Pdlim5), and that phosphomimetic Pdlim5 impairs cell migration by disrupting the Rac1-Arp2/3 signalling pathway.

  • Yi Yan
  • , Osamu Tsukamoto
  •  & Seiji Takashima

• Article | 29 January 2015

  The cleavage pattern of TDP-43 determines its rate of clearance and cytotoxicity

  TAR DNA-binding protein of 43 kDa (TDP-43) and its C-terminal fragment of 25 kDa (CTF25) play critical roles in several neurodegenerative diseases but the cleavage site that generates CTF25 remains undetermined. Here the authors show that caspase-4 cleaves TDP-43 after Aps174 generating CTF25, and this leads to TDP-43 clearance and increased cell viability.

  • Quan Li
  • , Moe Yokoshi
  •  & Yukio Kawahara

• Article | 28 January 2015

  ADAM8 as a drug target in pancreatic cancer

  Expression of ADAM8, a metalloprotease disintegrin, correlates with worse prognosis in pancreatic adenocarcinoma (PDAC). Here Schlomann et al. show that ADAM8 promotes PDAC invasiveness, and develop a peptide inhibitor that blocks ADAM8 function and impedes PDAC progression in mouse models.

  • Uwe Schlomann
  • , Garrit Koller
  •  & Jörg W. Bartsch

• Article | 27 January 2015

  Herpes simplex virus enhances chemokine function through modulation of receptor trafficking and oligomerization

  Herpes simplex viruses cause a variety of diseases, from cold sores to encephalitis. Here, Martinez-Martin et al. show that the viral protein gG binds to cell surface glycosaminoglycans and induces chemokine receptor clustering, enhancing chemokine function and thus modulating the immune response.

  • Nadia Martinez-Martin
  • , Abel Viejo-Borbolla
  •  & Antonio Alcamí

• Article | 23 January 2015

  An IL-27/NFIL3 signalling axis drives Tim-3 and IL-10 expression and T-cell dysfunction

  Tim-3 is an inhibitory molecule that suppresses T-cell responses. Here the authors show that the cytokine IL-27, acting through the transcription factor NFIL3, induces Tim-3 in vivo, and that IL-27-conditioned Th1 cells have poor effector function.

  • Chen Zhu
  • , Kaori Sakuishi
  •  & Vijay K. Kuchroo

• Article | 22 January 2015

  Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity

  Immune activation must be carefully tuned to respond to infection and restrained to prevent tissue damage. Here the authors show that autophagy has a role in the immune response to Candida albicans, activating NFκB in macrophages by sequestering the NFκB inhibitor A20.

  • Masashi Kanayama
  • , Makoto Inoue
  •  & Mari L. Shinohara

• Article | 22 January 2015

  Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci

  Alopecia areata (AA) is a common autoimmune disease with a known genetic component. Here, the authors analyse 3,253 AA patients and 7,543 healthy controls, and identify two new risk loci and disrupted immune response pathways associated with the disease.

  • Regina C. Betz
  • , Lynn Petukhova
  •  & Angela M. Christiano

• Article | 21 January 2015

  Internalization and vacuolar targeting of the brassinosteroid hormone receptor BRI1 are regulated by ubiquitination

  Ubiquitination of cargo proteins regulates endocytosis in yeast and mammalian cells, however the extent to which this applies to plants is less clear. Martins et al. show that both internalization and vacuolar targetting of the Arabidopsisbrassinosteroid receptor BRI1 are regulated by ubiquitination.

  • Sara Martins
  • , Esther M. N. Dohmann
  •  & Grégory Vert

• Article
  20 January 2015 | Open Access

  Intracellular CD24 disrupts the ARF–NPM interaction and enables mutational and viral oncogene-mediated p53 inactivation

  P53 is a tumour suppressor that is frequently mutated or downregulated in cancer. Here, Wang et al. show that CD24, a molecule frequently overexpressed in cancer, promotes p53 degradation by disrupting a regulatory ARF–MDM2 interaction, and silencing CD24 prevents the downregulation of p53.

  • Lizhong Wang
  • , Runhua Liu
  •  & Yang Liu

• Article | 20 January 2015

  Clustering of CARMA1 through SH3–GUK domain interactions is required for its activation of NF-κB signalling

  Activating mutations in the NF-κB regulator CARMA1 are associated with a form of B-cell lymphoma. Hara et al. show that both physiological and oncogenic CARMA1 signalling can be inhibited by preventing its activation-induced clustering, which is mediated by its SH3 and GUK domains.

  • Hiromitsu Hara
  • , Tadashi Yokosuka
  •  & Takashi Saito

• Article | 20 January 2015

  The mitochondrial uniporter controls fight or flight heart rate increases

  Animals react to threats by increasing their heart rate. Wu et al. show that mitochondrial calcium uptake via a highly selective ion channel, the mitochondrial calcium uniporter, stimulates metabolism in cardiac pacemaker cells and is essential for physiological pulse acceleration but not resting heart rate.

  • Yuejin Wu
  • , Tyler P. Rasmussen
  •  & Mark E. Anderson

• Article | 20 January 2015

  PFKFB4 controls embryonic patterning via Akt signalling independently of glycolysis

  PFKFB4 is an enzyme known to regulate glycolysis. The authors reveal a surprising new role for this protein in global patterning of dorsal ectoderm in frogs that is mediated by Akt signalling and independent of glycolysis.

  • Caterina Pegoraro
  • , Ana Leonor Figueiredo
  •  & Anne H. Monsoro-Burq

• Article
  20 January 2015 | Open Access

  The unexpected role of polyubiquitin chains in the formation of fibrillar aggregates

  Ubiquitin is a stable and soluble protein, but it is commonly found in inclusion bodies in neurodegenerative disorders and cancer. Here, Morimoto et al. report that increasing ubiquitin chain length leads to the formation of amyloid-like fibrils, which are degraded by an autophagy mechanism.

  • Daichi Morimoto
  • , Erik Walinda
  •  & Masahiro Shirakawa

• Article | 20 January 2015

  DNase II-dependent DNA digestion is required for DNA sensing by TLR9

  Discrimination between self and microbial DNA by innate receptors such as TLR9 relies on intracellular compartmentalization to increase specificity. Chan et al. show that activation of TLR9 by DNA ligands requires their processing by endolysosomal DNase II, restricting TLR9 activation to this organelle.

  • Mei Po Chan
  • , Masahiro Onji
  •  & Kensuke Miyake

• Article | 19 January 2015

  Mammalian frataxin directly enhances sulfur transfer of NFS1 persulfide to both ISCU and free thiols

  The protein frataxin has a role in iron–sulfur clusters biosynthesis that is still elusive. Here, the authors present a novel alkylation assay for the detection of persulfide, an intermediate in this process, and describe the function of frataxin in the control of persulfide transfer.

  • Aubérie Parent
  • , Xavier Elduque
  •  & Benoit D’Autréaux

• Article | 19 January 2015

  mab21-l3 regulates cell fate specification of multiciliate cells and ionocytes

  The Notch signalling pathway has important roles in embryonic development. Here the authors show that an evolutionarily conserved gene, mab21-l3, is inhibited by Notch signalling and regulates specification of developing multiciliate cells and ion-transporting ionocytes in frog embryos.

  • Chika Takahashi
  • , Morioh Kusakabe
  •  & Eisuke Nishida

• Article
  14 January 2015 | Open Access

  RNA export factor Ddx19 is required for nuclear import of the SRF coactivator MKL1

  Nuclear import of transcriptional regulators and export of mRNA are essential steps for the manufacture of proteins in the cytoplasm. Here, Rajakylä et al.link these two activities by showing that the mRNA export factor Ddx19 promotes the nuclear import of the transcriptional coactivator MKL1.

  • Eeva Kaisa Rajakylä
  • , Tiina Viita
  •  & Maria K. Vartiainen

• Article
  09 January 2015 | Open Access

  Tropomodulin3 is a novel Akt2 effector regulating insulin-stimulated GLUT4 exocytosis through cortical actin remodeling

  Insulin-stimulated GLUT4-storage vesicle fusion with the plasma membrane depends on activity of Akt2 and its downstream effectors. Here Lim et al.identify the actin-capping protein tropomodulin 3 as a novel Akt2 effector that remodels cortical actin to help facilitate GLUT4 membrane insertion.

  • Chun-Yan Lim
  • , Xuezhi Bi
  •  & Weiping Han

• Article | 09 January 2015

  Vasculopathy-associated hyperangiotensinemia mobilizes haematopoietic stem cells/progenitors through endothelial AT₂R and cytoskeletal dysregulation

  Increased levels of haematopoietic stem and progenitor cells in the blood have been linked to some forms of organ failure. Here, the authors show that the hormone angiotensin II increases mobilization of haematopoietic stem and progenitor cells by inducing cytoskeletal changes in bone marrow cells.

  • Kyung Hee Chang
  • , Ramesh C Nayak
  •  & Jose A Cancelas

• Article
  09 January 2015 | Open Access

  Innate sensing of microbial products promotes wound-induced skin cancer

  Inflammation and wounding can promote cancer development, but the underlying mechanisms are unclear. Here Hoste et al.show that leukocytes sensing flagellin, a component of bacteria, play a key role in inducing skin cancer in the context of wounding and chronic inflammation.

  • Esther Hoste
  • , Esther N. Arwert
  •  & Fiona M. Watt

• Article
  07 January 2015 | Open Access

  ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling

  Driver mutations in early T-cell precursor leukaemia (ETP-ALL) are poorly characterized. Here the authors show that Zeb2overexpression is often found in ETP-ALL, can recapitulate the disease in transgenic mice and confers survival advantage by upregulating IL-7 signalling.

  • Steven Goossens
  • , Enrico Radaelli
  •  & Jody J. Haigh

• Article | 07 January 2015

  A lysine-rich motif in the phosphatidylserine receptor PSR-1 mediates recognition and removal of apoptotic cells

  The phosphatidylserine receptor PSR-1 has been proposed to mediate recognition of apoptotic cells by phagocytes; however, this function has been contested. Yang et al. identify a lysine-rich motif in C. elegansPSR-1 that binds phosphatidylserine, and show that this motif is required for its phagocytic function.

  • Hengwen Yang
  • , Yu-Zen Chen
  •  & Ding Xue

• Article
  06 January 2015 | Open Access

  Rb and FZR1/Cdh1 determine CDK4/6-cyclin D requirement in C. elegans and human cancer cells

  In most human tumours, the cell cycle regulators Cdk4/6-cyclinD are overactive. Here the authors use C. elegansas a model system to identify downstream regulators that are critical in the response of tumour cells to Cdk4/6 inhibitors.

  • Inge The
  • , Suzan Ruijtenberg
  •  & Sander van den Heuvel

• Article | 05 January 2015

  Filopodia-based Wnt transport during vertebrate tissue patterning

  Distribution of Wnt morphogens in tissues is often graded, but it is unclear how these secreted factors move to form concentration gradients. Here, the authors show that Wnt8a is transported on actin-based filopodia, known also as cytonemes, that contact the signal-receiving cells during zebrafish gastrulation.

  • Eliana Stanganello
  • , Anja I. H. Hagemann
  •  & Steffen Scholpp

• Article | 05 January 2015

  Cyclin F suppresses B-Myb activity to promote cell cycle checkpoint control

  Cells respond to DNA damage by activating cell cycle checkpoints. Here, the authors show that the F-box protein cyclin F suppresses the B-Myb/cyclin A pathway to ensure a DNA damage-induced checkpoint response in the G2 phase of the cell cycle.

  • Ditte Kjærsgaard Klein
  • , Saskia Hoffmann
  •  & Claus Storgaard Sørensen

• Article
  23 December 2014 | Open Access

  Sequential actions of β-catenin and Bmp pattern the oral nerve net in Nematostella vectensis

  The bilaterian central nervous system is thought to have evolved from a cnidarian-like ancestor, but the mechanisms of neural induction in cnidarians are largely unknown. Here the authors study the cnidarian Nematostella vectensisand show that β-catenin signalling is crucial for the early induction of its embryonic nervous system, suggesting evolutionary roots for this pathway.

  • Hiroshi Watanabe
  • , Anne Kuhn
  •  & Thomas W. Holstein

• Article | 23 December 2014

  Mechanism of Ca²⁺-triggered ESCRT assembly and regulation of cell membrane repair

  Mechanical activity predisposes muscle cell membranes to damage, which is repaired by a poorly defined Ca²⁺-dependent mechanism. Scheffer et al. describe the machinery for Ca²⁺-induced assembly of ESCRT III membrane remodelling complex at damaged cell membranes, which facilitates repair.

  • Luana L. Scheffer
  • , Sen Chandra Sreetama
  •  & Jyoti K. Jaiswal

• Article | 22 December 2014

  Critical role of histone demethylase Jmjd3 in the regulation of CD4⁺ T-cell differentiation

  The histone demethylase Jmjd3 is involved in many biological processes. Here, the authors generate T cell-specific Jmjd3-deficient mice and show that Jmjd3 has a role in T-cell function and in the differentiation and interconversion of T-cell subsets in the intestine.

  • Qingtian Li
  • , Jia Zou
  •  & Rong-Fu Wang

• Article
  19 December 2014 | Open Access

  The Escherichia coli effector EspJ blocks Src kinase activity via amidation and ADP ribosylation

  Non-receptor tyrosine kinases such as Src play fundamental roles in host–pathogen interactions and phagocytosis. Here, Young et al. show that an enteropathogenic Escherichia coli(EPEC) protein, EspJ, inhibits Src activity by simultaneous amidation and ADP ribosylation of a conserved residue on the kinase.

  • Joanna C. Young
  • , Abigail Clements
  •  & Gad Frankel

• Article
  18 December 2014 | Open Access

  The tumour suppressor DLC2 ensures mitotic fidelity by coordinating spindle positioning and cell–cell adhesion

  Epithelial cells must position their mitotic spindle correctly to maintain cell–cell adhesion. Here Vitiello et al. show that the tumour suppressor DLC2 and the mitotic kinesin Kif1b coordinate microtubule–actin interactions upstream of mDia3, guiding spindle positioning and mitotic fidelity.

  • Elisa Vitiello
  • , Jorge G. Ferreira
  •  & Karl Matter

• Article
  17 December 2014 | Open Access

  Targeting β-catenin signaling for therapeutic intervention in MEN1-deficient pancreatic neuroendocrine tumours

  MEN1 gene encodes menin, a nuclear scaffold protein that regulates transcription and is often inactivated in pancreatic neuroendocrine tumours (PNETs). Here Jiang et al. show that MEN1-driven PNET development involves activation of β-catenin, and that β-catenin deletion ameliorates the disease.

  • Xiuli Jiang
  • , Yanan Cao
  •  & Guang Ning

• Article
  17 December 2014 | Open Access

  The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes

  The contribution of signal strength on cell fate decisions is often not reflected in signalling networks. By combining mathematical simulation and biochemical experiments in cultured adult cardiomyocytes, Shin et al. show that the concentration of a β-adrenergic receptor agonist affects the expression of Bcl-2, influencing the balance between cell survival and death.

  • Sung-Young Shin
  • , Taeyong Kim
  •  & Do Han Kim

• Article | 17 December 2014

  Translocation between PI(4,5)P₂-poor and PI(4,5)P₂-rich microdomains during store depletion determines STIM1 conformation and Orai1 gating

  The Orai1 Ca²⁺ channel is activated by STIM1 in response to Ca²⁺ release from the ER. Here Maléth et al.show that Orai1 inactivation occurs by translocation to PI(4,5)P2-rich plasma membrane microdomains, which facilitates recruitment of SARAF, a negative regulator of STIM1 function.

  • Jozsef Maléth
  • , Seok Choi
  •  & Malini Ahuja

• Article
  17 December 2014 | Open Access

  A molecular toggle after exocytosis sequesters the presynaptic syntaxin1a molecules involved in prior vesicle fusion

  Synaptic vesicle fusion involves a multi-protein assembly called the SNARE complex that is tightly regulated both spatially and temporally. Here Kavanagh et al. show that after vesicle fusion and SNARE complex disassembly in the synapse, the SNARE protein syntaxin1a is sequestered in a monomeric form by munc18-1, preventing ectopic SNARE complex assembly.

  • Deirdre M. Kavanagh
  • , Annya M. Smyth
  •  & Rory R. Duncan

• Article | 16 December 2014

  Direct conversion of mouse and human fibroblasts to functional melanocytes by defined factors

  Some skin pigment disorders such as vitiligo are caused by the loss of melanocytes, the pigment-producing cells in the skin. Here the authors present an approach to directly convert mouse and human dermal fibroblasts into functional melanocytes.

  • Ruifeng Yang
  • , Ying Zheng
  •  & Xiaowei Xu

• Article | 16 December 2014

  BMP signalling regulates the pre-implantation development of extra-embryonic cell lineages in the mouse embryo

  BMP signalling is important in early post-implantation embryonic development. Here the authors perform mRNA sequencing of inside and outside cells of pre-implantation mouse embryos and show that BMP signalling is critical for the development of the two extra-embryonic lineages at this early stage.

  • Sarah J. L. Graham
  • , Krzysztof B. Wicher
  •  & Magdalena Zernicka-Goetz

• Article | 16 December 2014

  An ecdysone-responsive nuclear receptor regulates circadian rhythms in Drosophila

  The mammalian circadian clock is influenced by nuclear receptors such as Rev-Erb. Here Kumar et al. show that ecdysone-induced protein 75 (E75), a fly homologue of Rev-Erb, regulates circadian rhythms in Drosophila, and demonstrate that E75 protects the clock against environmental stressors.

  • Shailesh Kumar
  • , Dechun Chen
  •  & Amita Sehgal

• Article | 15 December 2014

  STAT3 restrains RANK- and TLR4-mediated signalling by suppressing expression of the E2 ubiquitin-conjugating enzyme Ubc13

  The transcription factor STAT3 regulates production of inflammatory cytokines by modulating NF-κB signalling. Here the authors show that STAT3 is a transcriptional repressor of the E2 ubiquitin-conjugating enzyme Ubc13, modulating NF-κB by regulating Ubc13 abundance.

  • Huiyuan Zhang
  • , Hongbo Hu
  •  & Stephanie S. Watowich

• Article | 15 December 2014

  Constitutive and ligand-induced EGFR signalling triggers distinct and mutually exclusive downstream signalling networks

  Epidermal growth factor receptor (EGFR) elicits the signalling function after dimerization and activation of its kinase activity and perturbations in this pathway are often found in cancer. Here the authors describe two distinct and mutually exclusive modes of EGFR signalling due to a switch of EGFR-associated proteins with the ligand.

  • Sharmistha Chakraborty
  • , Li Li
  •  & Amyn A. Habib

• Article | 15 December 2014

  Phosphorylation of LRRK2 by casein kinase 1α regulates trans-Golgi clustering via differential interaction with ARHGEF7

  The kinase LRRK2 is implicated in Parkinson’s disease progression and is known to be phosphorylated. Chia et al.show that this phosphorylation is mediated by the kinase CK1a, and is required for the recruitment of LRRK2 to Golgi-derived vesicles, suggesting a role for this protein in Golgi maintenance.

  • Ruth Chia
  • , Sara Haddock
  •  & Mark R. Cookson