'The goal of this work was to determine the effect of nonablative syngeneic transplantation of young bone marrow (BM) to laboratory animals (mice) of advanced age upon maximum duration of their lifespan. To do this, transplantation of 100 million nucleated cells from BM of young syngeneic donors to an old ... More
Non-Toxic and Ultra-Small Biosilver Nanoclusters Trigger Apoptotic Cell Death in Fluconazole-Resistant Candida albicans via Ras Signaling.
AuthorsSingh BR, Gupta VK, Deeba F, Bajpai R, Pandey V, Naqvi AH, Upreti DK, Gathergood N, Jiang Y, El Enshasy HA, Sholkamy EN, Mostafa AA, Hesham AE, Singh BN,
JournalBiomolecules
PubMed ID30769763
'Silver-based nanostructures are suitable for many biomedical applications, but to be useful therapeutic agents, the high toxicity of these nanomaterials must be eliminated. Here, we biosynthesize nontoxic and ultra-small silver nanoclusters (rsAg@NCs) using metabolites of usnioid lichen (a symbiotic association of algae and fungi) that exhibit excellent antimicrobial activity against ... More
AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A.
AuthorsDavies AK, Itzhak DN, Edgar JR, Archuleta TL, Hirst J, Jackson LP, Robinson MS, Borner GHH,
JournalNat Commun
PubMed ID30262884
'Adaptor protein 4 (AP-4) is an ancient membrane trafficking complex, whose function has largely remained elusive. In humans, AP-4 deficiency causes a severe neurological disorder of unknown aetiology. We apply unbiased proteomic methods, including ''Dynamic Organellar Maps'', to find proteins whose subcellular localisation depends on AP-4. We identify three transmembrane ... More
A Novel Three-Dimensional Immune Oncology Model for High-Throughput Testing of Tumoricidal Activity.
AuthorsSherman H, Gitschier HJ, Rossi AE,
JournalFront Immunol
PubMed ID29740450
'The latest advancements in oncology research are focused on autologous immune cell therapy. However, the effectiveness of this type of immunotherapy for cancer remediation is not equivalent for all patients or cancer types. This suggests the need for better preclinical screening models that more closely recapitulate in vivo tumor biology. ... More
Analysis of novel endosome-to-Golgi retrieval genes reveals a role for PLD3 in regulating endosomal protein sorting and amyloid precursor protein processing.
AuthorsMukadam AS, Breusegem SY, Seaman MNJ,
JournalCell Mol Life Sci
PubMed ID29368044
'The processing of amyloid precursor protein (APP) to the neurotoxic pro-aggregatory Aß peptide is controlled by the mechanisms that govern the trafficking and localisation of APP. We hypothesised that genes involved in endosomal protein sorting could play an important role in regulating APP processing and, therefore, analysed ~ 40 novel endosome-to-Golgi retrieval ... More
DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways.
AuthorsDu F, Sun L, Chu Y, Li T, Lei C, Wang X, Jiang M, Min Y, Lu Y, Zhao X, Nie Y, Fan D,
JournalCancer Commun (Lond)
PubMed ID29976242
Gastric cancer (GC) is one of the most common malignancies worldwide, particularly in China. DNA damage-inducible transcript 4 (DDIT4) is a mammalian target of rapamycin inhibitor and is induced by various cellular stresses; however, its critical role in GC remains poorly understood. The present study aimed to investigate the potential ... More
Super-multiplexed fluorescence microscopy via photostability contrast.
AuthorsOrth A, Ghosh RN, Wilson ER, Doughney T, Brown H, Reineck P, Thompson JG, Gibson BC,
JournalBiomed Opt Express
PubMed ID29984077
Fluorescence microscopy is widely used to observe and quantify the inner workings of the cell. Traditionally, multiple types of cellular structures or biomolecules are visualized simultaneously in a sample by using spectrally distinct fluorescent labels. The wide emission spectra of most fluorophores limits spectral multiplexing to four or five labels ... More
The WDR11 complex facilitates the tethering of AP-1-derived vesicles.
AuthorsNavarro Negredo P, Edgar JR, Manna PT, Antrobus R, Robinson MS,
JournalNat Commun
PubMed ID29426865
Vesicluar transport of proteins from endosomes to the trans-Golgi network (TGN) is an essential cellular pathway, but much of its machinery is still unknown. A screen for genes involved in endosome-to-TGN trafficking produced two hits, the adaptor protein-1 (AP-1 complex), which facilitates vesicle budding, and WDR11. Here we demonstrate that ... More
Patients with densely innervated tumors suffer with increased metastasis and decreased survival as compared to those with less innervated tumors. We hypothesize that in some tumors, nerves are acquired by a tumor-induced process, called axonogenesis. Here, we use PC12 cells as an in vitro neuronal model, human tumor samples and ... More
Generation of three-dimensional human neuronal cultures: application to modeling CNS viral infections.
AuthorsD'Aiuto L, Naciri J, Radio N, Tekur S, Clayton D, Apodaca G, Di Maio R, Zhi Y, Dimitrion P, Piazza P, Demers M, Wood J, Chu C, Callio J, McClain L, Yolken R, McNulty J, Kinchington P, Bloom D, Nimgaonkar V,
JournalStem Cell Res Ther
PubMed ID29751846
A variety of neurological disorders including neurodegenerative diseases and infection by neurotropic viruses can cause structural and functional changes in the central nervous system (CNS), resulting in long-term neurological sequelae. An improved understanding of the pathogenesis of these disorders is important for developing efficacious interventions. Human induced pluripotent stem cells ... More
Identification of thiostrepton as a pharmacological approach to rescue misfolded alpha-sarcoglycan mutant proteins from degradation.
AuthorsHoch L, Henriques SF, Bruge C, Marsolier J, Benabides M, Bourg N, Tournois J, Mahé G, Morizur L, Jarrige M, Bigot A, Richard I, Nissan X,
JournalSci Rep
PubMed ID31061434
Limb-girdle muscular dystrophy type 2D (LGMD2D) is characterized by a progressive proximal muscle weakness. LGMD2D is caused by mutations in the gene encoding a-sarcoglycan (a-SG), a dystrophin-associated glycoprotein that plays a key role in the maintenance of sarcolemma integrity in striated muscles. We report here on the development of a ... More
High-throughput isolation of giant viruses using high-content screening.
AuthorsFrancis R, Ominami Y, Bou Khalil JY, La Scola B,
JournalCommun Biol
PubMed ID31240254
The race to discover and isolate giant viruses began 15 years ago. Metagenomics is counterbalancing coculture, with the detection of giant virus genomes becoming faster as sequencing technologies develop. Since the discovery of giant viruses, many efforts have been made to improve methods for coculturing amebas and giant viruses, which ... More
Combination treatment of the oral CHK1 inhibitor, SRA737 and low dose gemcitabine, enhances the effect of PD-L1 blockade by modulating the immune microenvironment in small cell lung cancer.
AuthorsSen T, Della Corte CM, Milutinovic S, Cardnell RJ, Diao L, Ramkumar K, Gay CM, Stewart CA, Fan Y, Shen L, Hansen RJ, Strouse B, Hedrick MP, Hassig CA, Heymach JV, Wang J, Byers LA,
JournalJ Thorac Oncol
PubMed ID31470128
Despite the enthusiasm surrounding cancer immunotherapy, most small cell lung cancer (SCLC) patients show very modest response to immune checkpoint inhibitor monotherapy treatment. There is therefore growing interest in combining immune checkpoint blockade (ICB) with chemotherapy and other treatments to enhance ICB efficacy. Based on favorable clinical trial results, chemotherapy ... More
A Novel Three-Dimensional Glioma Blood-Brain Barrier Model for High-Throughput Testing of Tumoricidal Capability.
AuthorsSherman H, Rossi AE,
JournalFront Oncol
PubMed ID31131260
The blood-brain barrier (BBB) limits passage of substances between general circulation and the brain extracellular fluid, maintaining homeostasis in neural tissues and providing a defense against potential toxins. However, the protection provided by the BBB often prevents conventional chemotherapeutics from reaching brain tumors which makes brain cancers one of the ... More
No evidence for cell-to-cell transmission of the unfolded protein response in cell culture.
Authorsvan Ziel AM, Wolzak K, Nölle A, Hoetjes PJ, Berenjeno-Correa E, van Anken E, Struys EA, Scheper W,
JournalJ Neurochem
PubMed ID31442299
The unfolded protein response (UPR) is one of the major cell-autonomous proteostatic stress responses. The UPR has been implicated in the pathogenesis of neurodegenerative diseases and is therefore actively investigated as therapeutic target. In this respect, cell non-autonomous effects of the UPR including the reported cell-to-cell transmission of UPR activity may ... More
Unconventional secretion factor GRASP55 is increased by pharmacological unfolded protein response inducers in neurons.
Authorsvan Ziel AM, Largo-Barrientos P, Wolzak K, Verhage M, Scheper W,
JournalSci Rep
PubMed ID30733486
Accumulation of misfolded proteins in the endoplasmic reticulum (ER), defined as ER stress, results in activation of the unfolded protein response (UPR). UPR activation is commonly observed in neurodegenerative diseases. ER stress can trigger unconventional secretion mediated by Golgi reassembly and stacking proteins (GRASP) relocalization in cell lines. Here we ... More
Replication Study: Wnt activity defines colon cancer stem cells and is regulated by the microenvironment.
AuthorsEssex A, Pineda J, Acharya G, Xin H, Evans J, Iorns E, Tsui R, Denis A, Perfito N, Errington TM, Iorns E, Tsui R, Denis A, Perfito N, Errington TM,
JournalElife
PubMed ID31215867
As part of the Reproducibility Project: Cancer Biology we published a Registered Report (Evans et al., 2015), that described how we intended to replicate selected experiments from the paper 'Wnt activity defines colon cancer stem cells and is regulated by the microenvironment' (Vermeulen et al., 2010). Here, we report the ... More
Isoscoparins R and S, two new ent-clerodane diterpenoids from Isodon scoparius.
AuthorsLi XR, Fu Q, Zhou M, Hu K, Du X, Li XN, Sun HD, Yue JB, Zhang HB, Puno PT,
JournalJ Asian Nat Prod Res
PubMed ID29873248
Two new ent-clerodane diterpenoids, named isoscoparins R and S (1 and 2), were isolated from the aerial parts of Isodon scoparius. Their structures were characterized mainly by analyzing the NMR and HRESIMS data, and the relative configuration of compound 1 was determined by single-crystal X-ray diffraction. Compound 2 showed weak ... More