Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood and cognitive functions is well established, viz. intrinsically photosensitive retinal ganglion cells (ipRGCs), the central mediators are unknown. Here we reveal that the direct effects of ... More
Comprehensive structure and functional adaptations of the yeast nuclear pore complex.
AuthorsAkey CW, Singh D, Ouch C, Echeverria I, Nudelman I, Varberg JM, Yu Z, Fang F, Shi Y, Wang J, Salzberg D, Song K, Xu C, Gumbart JC, Suslov S, Unruh J, Jaspersen SL, Chait BT, Sali A, Fernandez-Martinez J, Ludtke SJ, Villa E, Rout MP
JournalCell
PubMed ID34982960
Nuclear pore complexes (NPCs) mediate the nucleocytoplasmic transport of macromolecules. Here we provide a structure of the isolated yeast NPC in which the inner ring is resolved by cryo-EM at sub-nanometer resolution to show how flexible connectors tie together different structural and functional layers. These connectors may be targets for ... More
Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity.
AuthorsRingel AE, Drijvers JM, Baker GJ, Catozzi A, García-Cañaveras JC, Gassaway BM, Miller BC, Juneja VR, Nguyen TH, Joshi S, Yao CH, Yoon H, Sage PT, LaFleur MW, Trombley JD, Jacobson CA, Maliga Z, Gygi SP, Sorger PK, Rabinowitz JD, Sharpe AH, Haigis MC
JournalCell
PubMed ID33301708
Obesity is a major cancer risk factor, but how differences in systemic metabolism change the tumor microenvironment (TME) and impact anti-tumor immunity is not understood. Here, we demonstrate that high-fat diet (HFD)-induced obesity impairs CD8(+) T cell function in the murine TME, accelerating tumor growth. We generate a single-cell resolution ... More
Pathogenic ubiquitination of GSDMB inhibits NK cell bactericidal functions.
AuthorsHansen JM, de Jong MF, Wu Q, Zhang LS, Heisler DB, Alto LT, Alto NM
JournalCell
PubMed ID34022140
Gasdermin B (GSDMB) belongs to a large family of pore forming cytolysins that execute inflammatory cell death programs. While genetic studies have linked GSDMB polymorphisms to human disease, its function in the immunological response to pathogens remains poorly understood. Here, we report a dynamic host-pathogen conflict between GSDMB and the ... More
WNK kinases sense molecular crowding and rescue cell volume via phase separation.
AuthorsBoyd-Shiwarski CR, Shiwarski DJ, Griffiths SE, Beacham RT, Norrell L, Morrison DE, Wang J, Mann J, Tennant W, Anderson EN, Franks J, Calderon M, Connolly KA, Cheema MU, Weaver CJ, Nkashama LJ, Weckerly CC, Querry KE, Pandey UB, Donnelly CJ, Sun D, Rodan AR, Subramanya AR
JournalCell
PubMed ID36318922
When challenged by hypertonicity, dehydrated cells must recover their volume to survive. This process requires the phosphorylation-dependent regulation of SLC12 cation chloride transporters by WNK kinases, but how these kinases are activated by cell shrinkage remains unknown. Within seconds of cell exposure to hypertonicity, WNK1 concentrates into membraneless condensates, initiating ... More
Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage.
AuthorsNava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, Vihinen H, Jokitalo E, Li X, García Arcos JM, Hoffmann B, Merkel R, Niessen CM, Dahl KN, Wickström SA
JournalCell
PubMed ID32302590
Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a ... More
Thermus thermophilus Argonaute Functions in the Completion of DNA Replication.
AuthorsJolly SM, Gainetdinov I, Jouravleva K, Zhang H, Strittmatter L, Bailey SM, Hendricks GM, Dhabaria A, Ueberheide B, Zamore PD
JournalCell
PubMed ID32846159
In many eukaryotes, Argonaute proteins, guided by short RNA sequences, defend cells against transposons and viruses. In the eubacterium Thermus thermophilus, the DNA-guided Argonaute TtAgo defends against transformation by DNA plasmids. Here, we report that TtAgo also participates in DNA replication. In vivo, TtAgo binds 15â18 nt DNA guides derived ... More
Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic.
AuthorsLogan T, Simon MJ, Rana A, Cherf GM, Srivastava A, Davis SS, Low RLY, Chiu CL, Fang M, Huang F, Bhalla A, Llapashtica C, Prorok R, Pizzo ME, Calvert MEK, Sun EW, Hsiao-Nakamoto J, Rajendra Y, Lexa KW, Srivastava DB, van Lengerich B, Wang J, Robles-Colmenares Y, Kim DJ, Duque J, Lenser M, Earr TK, Nguyen H, Chau R, Tsogtbaatar B, Ravi R, Skuja LL, Solanoy H, Rosen HJ, Boeve BF, Boxer AL, Heuer HW, Dennis MS, Kariolis MS, Monroe KM, Przybyla L, Sanchez PE, Meisner R, Diaz D, Henne KR, Watts RJ, Henry AG, Gunasekaran K, Astarita G, Suh JH, Lewcock JW, DeVos SL, Di Paolo G
JournalCell
PubMed ID34450028
GRN mutations cause frontotemporal dementia (GRN-FTD) due to deficiency in progranulin (PGRN), a lysosomal and secreted protein with unclear function. Here, we found that Grn(â/â) mice exhibit a global deficiency in bis(monoacylglycero)phosphate (BMP), an endolysosomal phospholipid we identified as a pH-dependent PGRN interactor as well as a redox-sensitive enhancer of ... More
Pyramidal neurons form active, transient, multilayered circuits perturbed by autism-associated mutations at the inception of neocortex.
AuthorsMunz M, Bharioke A, Kosche G, Moreno-Juan V, Brignall A, Rodrigues TM, Graff-Meyer A, Ulmer T, Haeuselmann S, Pavlinic D, Ledergerber N, Gross-Scherf B, Rózsa B, Krol J, Picelli S, Cowan CS, Roska B
JournalCell
PubMed ID37071993
Cortical circuits are composed predominantly of pyramidal-to-pyramidal neuron connections, yet their assembly during embryonic development is not well understood. We show that mouse embryonic Rbp4-Cre cortical neurons, transcriptomically closest to layer 5 pyramidal neurons, display two phases of circuit assembly in vivo. At E14.5, they form a multi-layered circuit motif, composed ... More
Non-canonical β-adrenergic activation of ERK at endosomes.
AuthorsKwon Y, Mehta S, Clark M, Walters G, Zhong Y, Lee HN, Sunahara RK, Zhang J
JournalNature
PubMed ID36289326
G protein-coupled receptors (GPCRs), the largest family of signaling receptors, as well as important drug targets, are known to activate extracellular-signal-regulated kinase (ERK), a master regulator of cell proliferation and survival(1). However, the precise mechanisms underlying GPCR-mediated ERK activation are not clearly understood(2â4). Here we investigated how spatially organized β(2)-adrenergic ... More
Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner.
AuthorsGwon Y, Maxwell BA, Kolaitis RM, Zhang P, Kim HJ, Taylor JP
JournalScience (New York, N.Y.)
PubMed ID34739333
Stress granules are dynamic, reversible condensates composed of RNA and protein that assemble in eukaryotic cells in response to a variety of stressors and are normally disassembled after stress is removed. The composition and assembly of stress granules is well understood, but little is known about the mechanisms that govern ... More
Mitochondrial respiratory chain activity in idiopathic dilated cardiomyopathy.
AuthorsQuigley AF, Kapsa RM, Esmore D, Hale G, Byrne E
JournalJ Card Fail
PubMed ID10746819
Cardiomyopathy is well recognized in mitochondrial diseases in which it has been associated with defects of mitochondrial function, including cytochrome-c oxidase (COX) deficiencies. This study explores the respiratory chain activity, particularly of COX, in patients with cardiomyopathy to determine whether a relationship exists between respiratory enzyme activity and cardiac function. ... More
Hand2 Selectively Reorganizes Chromatin Accessibility to Induce Pacemaker-like Transcriptional Reprogramming.
AuthorsFernandez-Perez A, Sathe AA, Bhakta M, Leggett K, Xing C, Munshi NV
JournalCell Rep
PubMed ID31116981
'Gata4, Hand2, Mef2c, and Tbx5 (GHMT) can reprogram transduced fibroblasts into induced pacemaker-like myocytes (iPMs), but the underlying mechanisms remain obscure. Here, we explore the role of Hand2 in iPM formation by using a combination of transcriptome, genome, and biochemical assays. We found many shared transcriptional signatures between iPMs and ... More
PTBP1 contributes to spermatogenesis through regulation of proliferation in spermatogonia.
AuthorsSenoo M, Takijiri T, Yoshida N, Ozawa M, Ikawa M
JournalJ Reprod Dev
PubMed ID30416150
'Polypyrimidine tract-binding protein 1 (PTBP1) is a highly conserved RNA-binding protein that is a well-known regulator of alternative splicing. Testicular tissue is one of the richest tissues with respect to the number of alternative splicing mRNA isoforms, but the molecular role(s) of PTBP1 in the regulation of these isoforms during ... More
Transferrin receptor 1 is required for enucleation of mouse erythroblasts during terminal differentiation.
AuthorsAoto M, Iwashita A, Mita K, Ohkubo N, Tsujimoto Y, Mitsuda N,
JournalFEBS Open Bio
PubMed ID30761254
'Enucleation is the process whereby the nucleus is extruded from the erythroblast during late stage mammalian erythropoiesis. However, the specific signaling pathways involved in this process remain unclear. To better understand the mechanisms underlying erythroblast enucleation, we investigated erythroblast enucleation using both the spleens of adult mice with phenylhydrazine-induced anemia ... More
Rapid liquid biopsy for Mohs surgery: rare target cell separation from surgical margin lavage fluid with a high recovery rate and selectivity.
AuthorsZhou W, Liu Y, Ran M, Zhao X, Li H, Li H, Wang W
JournalLab Chip
PubMed ID30694285
'In melanoma surgery, it is difficult to identify residual scattered tumor cells at the surgical margin because of invasive growth. Mohs surgery, widely applied to increase the cure rate and decrease the recurrence rate of melanoma, involves examination of the tissue for tumor cells after tissue removal. Here, we established ... More
A case report of multiple primary prostate tumors with differential drug sensitivity.
AuthorsWilkinson S, Harmon SA, Terrigino NT, Karzai F, Pinto PA, Madan RA, VanderWeele DJ, Lake R, Atway R, Bright JR, Carrabba NV, Trostel SY, Lis RT, Chun G, Gulley JL, Merino MJ, Choyke PL, Ye H, Dahut WL, Turkbey B, Sowalsky AG
JournalNat Commun
PubMed ID32054861
'Localized prostate cancers are genetically variable and frequently multifocal, comprising spatially distinct regions with multiple independently-evolving clones. To date there is no understanding of whether this variability can influence management decisions for patients with prostate tumors. Here, we present a single case from a clinical trial of neoadjuvant intense androgen ... More
Pre-treatment with microRNA-181a Antagomir Prevents Loss of Parvalbumin Expression and Preserves Novel Object Recognition Following Mild Traumatic Brain Injury.
AuthorsGriffiths BB, Sahbaie P, Rao A, Arvola O, Xu L, Liang D, Ouyang Y, Clark DJ, Giffard RG, Stary CM
JournalNeuromolecular Med
PubMed ID30900118
'Mild traumatic brain injury (mTBI) can result in permanent impairment in memory and learning and may be a precursor to other neurological sequelae. Clinical treatments to ameliorate the effects of mTBI are lacking. Inhibition of microRNA-181a (miR-181a) is protective in several models of cerebral injury, but its role in mTBI ... More
Quantitative Analysis of Nuclear Lamins Imaged by Super-Resolution Light Microscopy.
AuthorsKittisopikul M, Virtanen L, Taimen P, Goldman RD
JournalCells
PubMed ID31003483
'The nuclear lamina consists of a dense fibrous meshwork of nuclear lamins, Type V intermediate filaments, and is ~14 nm thick according to recent cryo-electron tomography studies. Recent advances in light microscopy have extended the resolution to a scale allowing for the fine structure of the lamina to be imaged ... More
Assembly of Peripheral Actomyosin Bundles in Epithelial Cells Is Dependent on the CaMKK2/AMPK Pathway.
AuthorsRajakylä EK, Lehtimäki JI, Acheva A, Schaible N, Lappalainen P, Krishnan R, Tojkander S
JournalCell Rep
PubMed ID32209483
'Defects in the maintenance of intercellular junctions are associated with loss of epithelial barrier function and consequent pathological conditions, including invasive cancers. Epithelial integrity is dependent on actomyosin bundles at adherens junctions, but the origin of these junctional bundles is incompletely understood. Here we show that peripheral actomyosin bundles can ... More
Heterochromatin-Driven Nuclear Softening Protects the Genome against Mechanical Stress-Induced Damage.
AuthorsNava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, Vihinen H, Jokitalo E, Li X, García Arcos JM, Hoffmann B, Merkel R, Niessen CM, Dahl KN, Wickström SA
JournalCell
PubMed ID32302590
'Tissue homeostasis requires maintenance of functional integrity under stress. A central source of stress is mechanical force that acts on cells, their nuclei, and chromatin, but how the genome is protected against mechanical stress is unclear. We show that mechanical stretch deforms the nucleus, which cells initially counteract via a ... More
Multicomposite super-resolution microscopy: Enhanced Airyscan resolution with radial fluctuation and sample expansions.
AuthorsWang B, Yao L, Jing Y, Fei Y, Bai Q, Mi L, Ma J
JournalJ Biophotonics
PubMed ID31999066
'Either modulated illumination or temporal fluctuation analysis can assist super-resolution techniques in overcoming the diffraction limit of conventional optical microscopy. As they are not contradictory to each other, an effective combination of spatial and temporal super-resolution mechanisms would further improve the resolution of fluorescent images. Here, a super-resolution imaging method ... More
Notch signaling patterns head horn shape in the bull-headed dung beetle Onthophagus taurus.
AuthorsCrabtree JR, Macagno ALM, Moczek AP, Rohner PT, Hu Y
JournalDev Genes Evol
PubMed ID31960122
'Size and shape constitute fundamental aspects in the description of morphology. Yet while the developmental-genetic underpinnings of trait size, in particular with regard to scaling relationships, are increasingly well understood, those of shape remain largely elusive. Here we investigate the potential function of the Notch signaling pathway in instructing the ... More
Cytological Characterization of Arabidopsis arenosa Polyploids by SIM.
AuthorsMorgan C, Wegel E
JournalMethods Mol Biol
PubMed ID31583651
'Arabidopsis arenosa has recently become established as a model organism for investigating how meiosis has evolved to overcome the meiotic challenges faced by newly formed autotetraploids. Here, we describe a protocol for the preparation of spread, immunolabeled prophase I chromosomes from established A. arenosa autotetraploids for imaging with three-dimensional structured ... More
Dual Inhibitors-Loaded Nanotherapeutics that Target Kinase Signaling Pathways Synergize with Immune Checkpoint Inhibitor.
AuthorsRamesh A, Natarajan SK, Nandi D, Kulkarni A
JournalCell Mol Bioeng
PubMed ID31719920
'Immune checkpoint inhibitors that boost cytotoxic T cell-based immune responses have emerged as one of the most promising approaches in cancer treatment. However, it is increasingly being realized that T cell activation needs to be rationally combined with molecularly targeted therapeutics for a maximal anti-tumor outcome. Currently, two oncogenic drivers, ... More
Hippocampal sub-regional differences in the microRNA response to forebrain ischemia.
AuthorsArvola O, Kaidonis G, Xu L, Griffiths B, Stary CM
JournalMol Cell Neurosci
PubMed ID31128240
'Transient forebrain ischemia, as occurs with cardiac arrest and resuscitation, results in impaired cognitive function secondary to delayed neuronal cell death in hippocampal cornu ammonis-1 (CA1). Comparatively, hippocampal neurons in the adjacent dentate gyrus (DG) survive, suggesting that elucidating the molecular mechanisms underpinning hippocampal sub-regional differences in ischemic tolerance could ... More
Overexpressed vascular endothelial growth factor in adipose derived stem cells attenuates fibroblasts and skin injuries by ultraviolet radiation.
AuthorsXie X, Wang Y, Xia Y, Mao Y
JournalBiosci Rep
PubMed ID31266813
'Adipose-derived stem cells (ADSCs) and vascular endothelial growth factor (VEGF) contribute to the healing of wound. The purpose of the present study was to investigate the role of VEGF produced by ADSCs in the protection of fibroblasts and skin of mice from ultraviolet (UV) radiation. ADSCs and fibroblasts were extracted ... More
C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy.
AuthorsCali CP, Patino M, Tai YK, Ho WY, McLean CA, Morris CM, Seeley WW, Miller BL, Gaig C, Vonsattel JPG, White CL, Roeber S, Kretzschmar H, Troncoso JC, Troakes C, Gearing M, Ghetti B, Van Deerlin VM, Lee VM, Trojanowski JQ, Mok KY, Ling H, Dickson DW, Schellenberg GD, Ling SC, Lee EB
JournalActa Neuropathol
PubMed ID31327044
'Microsatellite repeat expansion disease loci can exhibit pleiotropic clinical and biological effects depending on repeat length. Large expansions in C9orf72 (100s-1000s of units) are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). However, whether intermediate expansions also contribute to neurodegenerative disease is not well ... More
Insertional mutagenesis in the zoonotic pathogen Chlamydia caviae.
'The ability to introduce targeted genetic modifications in microbial genomes has revolutionized our ability to study the role and mode of action of individual bacterial virulence factors. Although the fastidious lifestyle of obligate intracellular bacterial pathogens poses a technical challenge to such manipulations, the last decade has produced significant advances ... More
Sustained Release of Basic Fibroblast Growth Factor (bFGF) Encapsulated Polycaprolactone (PCL) Microspheres Promote Angiogenesis In Vivo.
AuthorsArunkumar P, Dougherty JA, Weist J, Kumar N, Angelos MG, Powell HM, Khan M
JournalNanomaterials (Basel)
PubMed ID31330782
'Coronary heart disease (CHD) is the leading cause of death in the Unites States and globally. The administration of growth factors to preserve cardiac function after myocardial infarction (MI) is currently being explored. Basic fibroblast growth factor (bFGF), a potent angiogenic factor has poor clinical efficacy due to its short ... More
Meta-Analysis and Experimental Validation Identified FREM2 and SPRY1 as New Glioblastoma Marker Candidates.
AuthorsVidak M, Jovcevska I, Samec N, Zottel A, Liovic M, Rozman D, Dzeroski S, Juvan P, Komel R,
JournalInt J Mol Sci
PubMed ID29734672
'Glioblastoma (GB) is the most aggressive brain malignancy. Although some potential glioblastoma biomarkers have already been identified, there is a lack of cell membrane-bound biomarkers capable of distinguishing brain tissue from glioblastoma and/or glioblastoma stem cells (GSC), which are responsible for the rapid post-operative tumor reoccurrence. In order to find ... More
Plin4-Dependent Lipid Droplets Hamper Neuronal Mitophagy in the MPTP/p-Induced Mouse Model of Parkinson's Disease.
AuthorsHan X, Zhu J, Zhang X, Song Q, Ding J, Lu M, Sun S, Hu G
JournalFront Neurosci
PubMed ID29967574
Epidemiological studies have shown that both lipid metabolism disorder and mitochondrial dysfunction are correlated with the pathogenesis of neurodegenerative diseases (NDDs), including Parkinson's disease (PD). Emerging evidence suggests that deposition of intracellular lipid droplets (LDs) participates in lipotoxicity and precedes neurodegeneration. Perilipin family members were recognized to facilitate LD movement ... More
Cholesterol and phosphatidylserine are engaged in adenoviral dodecahedron endocytosis.
AuthorsJedynak M, Worch R, Podsiadla-Bialoskórska M, Chroboczek J, Szolajska E
JournalBiochim Biophys Acta Biomembr
PubMed ID30409517
Adenoviral dodecahedron is a virus-like particle composed of twelve penton base proteins, derived from the capsid of human adenovirus type 3. Due to the high cell penetration capacity, it was used as a vector for protein, peptide and drug delivery. Two receptors are known to be involved in the endocytic ... More
Yap1 safeguards mouse embryonic stem cells from excessive apoptosis during differentiation.
AuthorsLeBlanc L, Lee BK, Yu AC, Kim M, Kambhampati AV, Dupont SM, Seruggia D, Ryu BU, Orkin SH, Kim J,
JournalElife
PubMed ID30561326
Approximately, 30% of embryonic stem cells (ESCs) die after exiting self-renewal, but regulators of this process are not well known. Yap1 is a Hippo pathway transcriptional effector that plays numerous roles in development and cancer. However, its functions in ESC differentiation remain poorly characterized. We first reveal that ESCs lacking ... More
Heterozygous Truncating Variants in POMP Escape Nonsense-Mediated Decay and Cause a Unique Immune Dysregulatory Syndrome.
AuthorsPoli MC, Ebstein F, Nicholas SK, de Guzman MM, Forbes LR, Chinn IK, Mace EM, Vogel TP, Carisey AF, Benavides F, Coban-Akdemir ZH, Gibbs RA, Jhangiani SN, Muzny DM, Carvalho CMB, Schady DA, Jain M, Rosenfeld JA, Emrick L, Lewis RA, Lee B, Zieba BA, Küry S, Krüger E, Lupski JR, Bostwick BL, Orange JS,
JournalAm J Hum Genet
PubMed ID29805043
The proteasome processes proteins to facilitate immune recognition and host defense. When inherently defective, it can lead to aberrant immunity resulting in a dysregulated response that can cause autoimmunity and/or autoinflammation. Biallelic or digenic loss-of-function variants in some of the proteasome subunits have been described as causing a primary immunodeficiency ... More
A virus-induced kidney disease model based on organ-on-a-chip: Pathogenesis exploration of virus-related renal dysfunctions.
AuthorsWang J, Wang C, Xu N, Liu ZF, Pang DW, Zhang ZL
JournalBiomaterials
PubMed ID31344514
Renal dysfunctions usually happen in viral infections and many viruses specially infect distal renal tubules, however the pathogenesis remains unknown. Here, in order to explore the pathogenesis of virus-related renal dysfunctions, a Pseudorabies Virus (PrV) induced kidney disease model was built on a distal tubule-on-a-chip (DTC), for the first time. ... More
Cell-Cell Adhesion and Myosin Activity Regulate Cortical Actin Assembly in Mammary Gland Epithelium on Concaved Surface.
AuthorsJung WH, Elawad K, Kang SH, Chen Y
JournalCells
PubMed ID31382444
It has been demonstrated that geometry can affect cell behaviors. Though curvature-sensitive proteins at the nanoscale are studied, it is unclear how cells sense curvature at the cellular and multicellular levels. To characterize and determine the mechanisms of curvature-dependent cell behaviors, we grow cells on open channels of the 60-µm ... More
Therapeutic Silencing of Centromere Protein X Ameliorates Hyperglycemia in Zebrafish and Mouse Models of Type 2 Diabetes Mellitus.
AuthorsZang L, Shimada Y, Nakayama H, Chen W, Okamoto A, Koide H, Oku N, Dewa T, Shiota M, Nishimura N
JournalFront Genet
PubMed ID31417608
Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia and is influenced by genetic and environmental factors. Optimum T2DM management involves early diagnosis and effective glucose-lowering therapies. Further research is warranted to improve our understanding of T2DM pathophysiology and reveal potential roles of genetic predisposition. We have previously developed ... More
Multinuclear Ru(ii) and Ir(iii) decorated tetraphenylporphyrins as efficient PDT agents.
AuthorsCabrera-González J, Soriano J, Conway-Kenny R, Wang J, Lu Y, Zhao J, Nogués C, Draper SM
JournalBiomater Sci
PubMed ID31187805
Two novel porphyrin-core systems were prepared by Sonogashira cross-coupling of the terminal alkyne groups of meso-tetra(4-ethynylphenyl)porphyrin-Zn(ii) (P-1) with halogenated Ru(ii)- or Ir(iii)-phenanthroline complexes. The resulting compounds (P-Ru and P-Ir) were spectroscopically characterised and their photophysical properties were investigated (? ... More
Growth and neurite stimulating effects of the neonicotinoid pesticide clothianidin on human neuroblastoma SH-SY5Y cells.
AuthorsHirano T, Minagawa S, Furusawa Y, Yunoki T, Ikenaka Y, Yokoyama T, Hoshi N, Tabuchi Y
JournalToxicol Appl Pharmacol
PubMed ID31626844
Neonicotinoids are one of most widely used pesticides targeting nicotinic acetylcholine receptors (nAChRs) of insects. Recent epidemiological evidence revealed increasing amounts of neonicotinoids detected in human samples, raising the critical question of whether neonicotinoids affect human health. We investigated the effects of a neonicotinoid pesticide clothianidin (CTD) on human neuroblastoma ... More
Daedalus and Gasz recruit Armitage to mitochondria, bringing piRNA precursors to the biogenesis machinery.
AuthorsMunafò M, Manelli V, Falconio FA, Sawle A, Kneuss E, Eastwood EL, Seah JWE, Czech B, Hannon GJ
JournalGenes Dev
PubMed ID31123065
The Piwi-interacting RNA (piRNA) pathway is a small RNA-based immune system that silences mobile genetic elements in animal germlines. piRNA biogenesis requires a specialized machinery that converts long single-stranded precursors into small RNAs of ~25-nucleotides in length. This process involves factors that operate in two different subcellular compartments: the nuage/Yb ... More
Tauopathy in the periaqueductal gray, kölliker-fuse nucleus and nucleus retroambiguus is not predicted by ultrasonic vocalization in tau-P301L mice.
AuthorsTrevizan-Baú P, Dhingra RR, Burrows EL, Dutschmann M, Stanic D
JournalBehav Brain Res
PubMed ID31004684
Upper airway and vocalization control areas such as the periaqueductal gray (PAG), kölliker-fuse nucleus (KF) and nucleus retroambiguus (NRA) are prone to developing tauopathy in mice expressing the mutant human tau P301L protein. Consequently, impaired ultrasonic vocalization (USV) previously identified in tau-P301L mice at the terminal disease stage of 8-9 ... More
Structural and Dynamical Signatures of Local DNA Damage in Live Cells.
AuthorsEaton JA, Zidovska A
JournalBiophys J
PubMed ID31818467
The dynamic organization of chromatin inside the cell nucleus plays a key role in gene regulation and genome replication, as well as maintaining genome integrity. Although the static folded state of the genome has been extensively studied, dynamical signatures of processes such as transcription or DNA repair remain an open ... More
Detection of mRNA Transfer Between Mammalian Cells in Coculture by Single-Molecule Fluorescent In Situ Hybridization (smFISH).
AuthorsHaimovich G, Gerst JE
JournalMethods Mol Biol
PubMed ID31407281
In eukaryotic cells, a small percentage of mRNA molecules can undergo transfer from one cell to another. mRNA transfer occurs primarily via membrane nanotubes, which are long thin protrusions that are produced by numerous cell types and can connect cells that can be up to hundreds of microns apart. Potentially, ... More
Enhancement of binding avidity by bivalent binding enables PrPSc-specific detection by anti-PrP monoclonal antibody 132.
AuthorsSuzuki A, Yamasaki T, Hasebe R, Horiuchi M
JournalPLoS One
PubMed ID31170247
Anti-prion protein (PrP) monoclonal antibody 132, which recognizes mouse PrP amino acids 119-127, enables us to reliably detect abnormal isoform prion protein (PrPSc) in cells or frozen tissue sections by immunofluorescence assay, although treatment with guanidinium salts is a prerequisite. Despite the benefit of this mAb, the mechanism of PrPSc-specific ... More
Muscle-Derived Extracellular Vesicles Influence Motor Neuron Regeneration Accuracy.
AuthorsMadison RD, Robinson GA
JournalNeuroscience
PubMed ID31454553
Extracellular vesicles are lipid bilayer-enclosed extracellular structures. Although the term extracellular vesicles is quite inclusive, it generally refers to exosomes (<200?nm), and microvesicles (~100-1000?nm). Such vesicles are resistant to degradation and can contain proteins, lipids, and nucleic acids. Although it was previously thought that the primary purpose of such vesicles ... More
Myristoylated alanine-rich C-kinase substrate effector domain phosphorylation regulates the growth and radiation sensitization of glioblastoma.
Glioblastoma harbors frequent alterations in receptor tyrosine kinases, phosphatidylinositol-3 kinase (PI3K) and phosphatase and tensin homolog (PTEN) that dysregulate phospholipid signaling driven tumor proliferation and therapeutic resistance. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a 32 kDa intrinsically unstructured protein containing a polybasic (+13) effector domain (ED), which regulates its electrostatic sequestration of phospholipid phosphatidylinositol (4,5)-bisphosphate ... More
3D Electrophysiological Measurements on Cells Embedded within Fiber-Reinforced Matrigel.
AuthorsSchaefer N, Janzen D, Bakirci E, Hrynevich A, Dalton PD, Villmann C
JournalAdv Healthc Mater
PubMed ID30637979
2D electrophysiology is often used to determine the electrical properties of neurons. In the brain however, neurons form extensive 3D networks. Thus, performing electrophysiology in a 3D environment provides a closer situation to the physiological condition and serves as a useful tool for various applications in the field of neuroscience. ... More
Optimized Ki-67 staining in murine cells: a tool to determine cell proliferation.
AuthorsGraefe C, Eichhorn L, Wurst P, Kleiner J, Heine A, Panetas I, Abdulla Z, Hoeft A, Frede S, Kurts C, Endl E, Weisheit CK
JournalMol Biol Rep
PubMed ID31093875
The reliable analysis of the cell cycle status has become increasingly relevant for scientific and clinical work, especially for the determination of tumor cell growth. One established method to characterize the proliferation activity of cells is the analysis of the Ki-67 protein. Ki-67 is expressed in the nucleus during the ... More
Expression of cholecystokinin by neurons in mouse spinal dorsal horn.
AuthorsGutierrez-Mecinas M, Bell AM, Shepherd F, Polgár E, Watanabe M, Furuta T, Todd AJ
JournalJ Comp Neurol
PubMed ID30734936
Excitatory interneurons account for the majority of dorsal horn neurons, and are required for perception of normal and pathological pain. We have identified largely non-overlapping populations in laminae I-III, based on expression of substance P, gastrin-releasing peptide, neurokinin B, and neurotensin. Cholecystokinin (CCK) is expressed by many dorsal horn neurons, ... More
Acute effects of milk polar lipids on intestinal tight junction expression: towards an impact of sphingomyelin through the regulation of IL-8 secretion?
AuthorsMilard M, Penhoat A, Durand A, Buisson C, Loizon E, Meugnier E, Bertrand K, Joffre F, Cheillan D, Garnier L, Viel S, Laugerette F, Michalski MC
JournalJ Nutr Biochem
PubMed ID30685581
Milk polar lipids (MPL) are specifically rich in milk sphingomyelin (MSM) which represents 24% of MPL. Beneficial effects of MPL or MSM have been reported on lipid metabolism, but information on gut physiology is scarce. Here we assessed whether MPL and MSM can impact tight junction expression. Human epithelial intestinal ... More
Solid Lipid Nanoparticles Surface Modification Modulates Cell Internalization and Improves Chemotoxic Treatment in an Oral Carcinoma Cell Line.
AuthorsArana L, Bayón-Cordero L, Sarasola LI, Berasategi M, Ruiz S, Alkorta I
JournalNanomaterials (Basel)
PubMed ID30897724
Solid lipid nanoparticles (SLN) present low toxicity, versatility to incorporate both lipophilic and hydrophilic drugs, controlled drug release and they are easy to scale-up. It is well known that the endocytosis pathway by which SLN are taken up and the subsequent subcellular distribution are crucial for the biological effect of ... More
Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles.
AuthorsLee JE, Cathey PI, Wu H, Parker R, Voeltz GK
JournalScience
PubMed ID32001628
Tethered interactions between the endoplasmic reticulum (ER) and other membrane-bound organelles allow for efficient transfer of ions and/or macromolecules and provide a platform for organelle fission. Here, we describe an unconventional interface between membraneless ribonucleoprotein granules, such as processing bodies (P-bodies, or PBs) and stress granules, and the ER membrane. ... More
Mixed-mode bacterial transmission in the common brooding coral Pocillopora acuta.
AuthorsDamjanovic K, Menéndez P, Blackall LL, van Oppen MJH
JournalEnviron Microbiol
PubMed ID31709681
Reef-building corals form associations with a huge diversity of microorganisms, which are essential for the survival and well-being of their host. While the acquisition patterns of Symbiodiniaceae microalgal endosymbionts are strongly linked to the coral's reproductive strategy, few studies have investigated the transmission mode of bacteria, especially in brooding species. ... More
Histamine-mediated autocrine signaling in mesenteric perilymphatic mast cells.
AuthorsPal S, Gasheva OY, Zawieja DC, Meininger CJ, Gashev AA
JournalAm J Physiol Regul Integr Comp Physiol
PubMed ID31913658
Lymphatic vessels play a critical role in mounting a proper immune response by trafficking peripheral immune cells to draining lymph nodes. Mast cells (MCs) are well known for their roles in type I hypersensitivity reactions but little is known about their secretory regulation in the lymphatic niche. MCs, as innate ... More
Modified application of Kawamoto's film method for super-resolution imaging of megakaryocytes in undecalcified bone marrow.
AuthorsMorodomi Y, Kanaji S, Won E, Kawamoto T, Kanaji T
JournalRes Pract Thromb Haemost
PubMed ID31989088
Super-resolution microscopy has enabled high-resolution imaging of the actin cytoskeleton in megakaryocytes and platelets. These technologies have extended our knowledge of thrombopoiesis and platelet spreading using megakaryocytes and platelets cultured in vitro on matrix proteins. However, for better understanding of megakaryocytopoiesis and platelet production, high-resolution imaging of cells in an ... More
Neuron-specific Kv1.1 deficiency is sufficient to cause epilepsy, premature death, and cardiorespiratory dysregulation.
AuthorsTrosclair K, Dhaibar HA, Gautier NM, Mishra V, Glasscock E
JournalNeurobiol Dis
PubMed ID31978607
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of epilepsy-related mortality, but the precise cellular substrates involved remain elusive. Epilepsy-associated ion channel genes with co-expression in brain and heart have been proposed as SUDEP candidate genes since they provide a singular unifying link between seizures and lethal cardiac ... More
Antitumor effect of baicalin from the Scutellaria baicalensis radix extract in B-acute lymphoblastic leukemia with different chromosomal rearrangements.
AuthorsOrzechowska BU, Wróbel G, Turlej E, Jatczak B, Sochocka M, Chaber R
JournalInt Immunopharmacol
PubMed ID31881375
Acute B-lymphoblastic leukemia (B-ALL) is the most common hematologic malignancy in children. Many cases of B-ALL harbor chromosomal translocations which are often critical determinants of prognosis. Most of them represent altered transcription factors that impact gene transcription or enhance signaling. B-ALLs harboring the mixed-lineage leukemia 1 (MLL1) gene rearrangements represent ... More
Somatostatin receptors (SSTR1-5) on inhibitory interneurons in the barrel cortex.
AuthorsLukomska A, Dobrzanski G, Liguz-Lecznar M, Kossut M
JournalBrain Struct Funct
PubMed ID31873798
Inhibitory interneurons in the cerebral cortex contain specific proteins or peptides characteristic for a certain interneuron subtype. In mice, three biochemical markers constitute non-overlapping interneuron populations, which account for 80-90% of all inhibitory cells. These interneurons express parvalbumin (PV), somatostatin (SST), or vasoactive intestinal peptide (VIP). SST is not only ... More
Biological response and cytotoxicity induced by lipid nanocapsules.
AuthorsSzwed M, Torgersen ML, Kumari RV, Yadava SK, Pust S, Iversen TG, Skotland T, Giri J, Sandvig K
JournalJ Nanobiotechnology
PubMed ID31907052
Lipid nanocapsules (LNCs) are promising vehicles for drug delivery. However, since not much was known about cellular toxicity of these nanoparticles in themselves, we have here investigated the mechanisms involved in LNC-induced intoxication of the three breast cancer cell lines MCF-7, MDA-MD-231 and MDA-MB-468. The LNCs used were made of ... More