6,607,347 results match your criteria Cell Biology Insights [Journal]

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Disordered APC/C-mediated cell cycle progression and IGF1/PI3K/AKT signalling are the potential basis of Sertoli cell-only syndrome.

Andrologia 2019 Apr 17:e13288. Epub 2019 Apr 17.

Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, China.

The cause of Sertoli cell-only syndrome (SCOS), a condition in which only Sertoli cells line the seminiferous tubules in the testis, is unknown. Three microarray data sets were downloaded from public databases and were used to compare SCOS and control group. A total of 291 genes differentially expressed (Log |FC| ≥ 1 and adjusted p value < 0. Read More

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http://dx.doi.org/10.1111/and.13288DOI Listing

Rare case of an oligospermic male with 46,XX/46,XY tetragametic chimerism.

Andrologia 2019 Apr 17:e13290. Epub 2019 Apr 17.

Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.

Chimerism, a rare human disorder, is assumed to be the result of an amalgamation of two separate zygotes in a single embryo. Studies have shown that the phenotypic spectrum of chimerism is variable and there is no definite genotype-phenotype correlation in patients with chimerism, therefore a majority of cases might remain undiagnosed. This study aims to investigate the possible mechanism of the chimerism in a 46,XX/46,XY infertile and phenotypically normal male, with 46,XX blood karyotype and normal spermatogenesis. Read More

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http://dx.doi.org/10.1111/and.13290DOI Listing

Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors.

Nature 2019 Apr 17. Epub 2019 Apr 17.

Molecular Pathology Unit, Massachusetts General Hospital, Charlestown, MA, USA.

CRISPR-Cas base editor technology enables targeted nucleotide alterations and is being rapidly deployed for research and potential therapeutic applications. The most widely used base editors induce DNA cytosine (C) deamination with rat APOBEC1 (rAPOBEC1) enzyme, which is targeted by a linked Cas protein-guide RNA (gRNA) complex. Previous studies of cytosine base editor (CBE) specificity have identified off-target DNA edits in human cells. Read More

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http://dx.doi.org/10.1038/s41586-019-1161-zDOI Listing
April 2019
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Clinical Experience of Immunotherapy Treatment: Efficacy and Toxicity Analysis of the Compassionate Use Program of Nivolumab in Patients with Advanced Squamous Cell Non-Small Cell Lung Cancer.

Oncol Res Treat 2019 Apr 17;42(5):243-254. Epub 2019 Apr 17.

Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.

Background: Anti-PD1 monoclonal antibody nivolumab is an approved therapy option for the treatment of advanced squamous cell non-small cell lung cancer (SQ-NSCLC) patients. Data outside clinical trials about therapy efficacy and safety in later therapy line treatments have rarely been described until now.

Methods: We performed a retrospective data analysis of patients who were enrolled into the nivolu-mab Compassionate Use Program (CUP) in Germany. Read More

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http://dx.doi.org/10.1159/000499321DOI Listing

Inhibition of HSF1 enhances repressive molecular mechanisms on POMC promoter.

Neuroendocrinology 2019 Apr 16. Epub 2019 Apr 16.

Background: Cushing´s Disease (CD) is caused by adrenocorticotropic hormone (ACTH)- secreting pituitary tumours. They express high levels of heat shock protein (HSP) 90 and heat shock factor 1 (HSF1) in comparison to the normal tissue counterpart, indicating activated cellular stress.

Aims: (1) to correlate HSF1 expression with clinical features and hormonal/radiological findings of CD and (2) to investigate the effects of HSF1 inhibition as a target for CD treatment. Read More

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http://dx.doi.org/10.1159/000500200DOI Listing

Determination of Circulating Endothelial Cells and Endothelial Progenitor Cells Using Multicolor Flow Cytometry in Patients with Thrombophilia.

Acta Haematol 2019 Apr 17:1-7. Epub 2019 Apr 17.

Institute of Medical Biochemistry and Laboratory Diagnostics, Thrombotic Center, General University Hospital, and First Faculty of Medicine, Charles University, Prague, Czech Republic.

Background/aims: Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) have been described as markers of endothelial damage and dysfunction in several diseases, including deep venous thrombosis. Their role in patients with known thrombophilia has not yet been evaluated. Both EPCs and CECs represent extremely rare cell populations. Read More

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http://dx.doi.org/10.1159/000499524DOI Listing

Electrical Stimulation Directs Migration, Enhances and Orients Cell Division and Upregulates the Chemokine Receptors CXCR4 and CXCR2 in Endothelial Cells.

J Vasc Res 2019 Apr 17;56(1):39-53. Epub 2019 Apr 17.

Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.

Natural direct current electric fields (DC EFs) within tissues undergoing angiogenesis have the potential to influence vessel formation, but how they affect endothelial cells is not clear. We therefore quantified behaviours of human umbilical vein endothelial cells (HUVEC) and human microvasculature endothelial cells (HMEC) stimulated by EFsin vitro. Both cell types migrated faster and toward the cathode; HUVECs responded to fields as low as 50mV/mm, but the HMEC threshold was 100 mV/mm. Read More

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http://dx.doi.org/10.1159/000495311DOI Listing

The Arginase Pathway in Neonatal Brain Hypoxia-Ischemia.

Dev Neurosci 2019 Apr 17:1-14. Epub 2019 Apr 17.

Department of Pediatrics, University of California San Francisco, San Francisco, California, USA.

Brain damage after hypoxia-ischemia (HI) occurs in an age-dependent manner. Neuroprotective strategies assumed to be effective in adults might have deleterious effects in the immature brain. In order to create effective therapies, the complex pathophysiology of HI in the developing brain requires exploring new mechanisms. Read More

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http://dx.doi.org/10.1159/000496467DOI Listing

Flow field perception based on the fish lateral line system.

Bioinspir Biomim 2019 Apr 17. Epub 2019 Apr 17.

Beihang University, Beijing, CHINA.

Fish are able to perceive the surrounding weak flow and pressure variations with their mechanosensory lateral line system, which consists of a superficial lateral line for flow velocity detection and a canal lateral line for flow pressure gradient perception. Achieving a better understanding of the flow field perception algorithms of the lateral line can contribute not only to the design of highly sensitive flow sensors, but also to the development of underwater smart skin with good hydrodynamic imaging properties. In this review, we discuss highly sensitive flow-sensing mechanisms for superficial and canal neuromasts and flow field perception algorithms. Read More

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http://dx.doi.org/10.1088/1748-3190/ab1a8dDOI Listing

Shear-induced alignment of collagen fibrils using 3D cell printing for corneal stroma tissue engineering.

Biofabrication 2019 Apr 17. Epub 2019 Apr 17.

Department of Mechanical Engineering, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, KOREA, Pohang, KOREA, REPUBLIC OF.

The microenvironments of tissues or organs are complex architectures comprised of structural proteins including collagen. Particularly, the cornea is organized in a lattice pattern of collagen fibrils which play a significant role in its transparency. This paper introduces a transparent bioengineered corneal structure for transplantation. Read More

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http://dx.doi.org/10.1088/1758-5090/ab1a8bDOI Listing

Inhibition of MRP4 alleviates sepsis-induced acute lung injury in rats.

Int Immunopharmacol 2019 Apr 14;72:211-217. Epub 2019 Apr 14.

Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China. Electronic address:

This study was undertaken to examine the regulatory role of multidrug resistance-associated protein 4 (MRP4) in an experimental model of sepsis-induced acute lung injury in rats. Sepsis was induced by cecal ligation and puncture in anesthetized rats. Animals were then randomly assigned to receive intravenous injection of vehicle or MRP4 inhibitor (MK571, 20 mg/kg). Read More

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http://dx.doi.org/10.1016/j.intimp.2019.04.009DOI Listing

Development of a sediment microbial fuel cell-based biosensor for simultaneous online monitoring of dissolved oxygen concentrations along various depths in lake water.

Sci Total Environ 2019 Apr 3;673:272-280. Epub 2019 Apr 3.

State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, China. Electronic address:

A novel multi-cathode, single-anode system integrating a sediment microbial fuel cell -based biosensor was developed for in-situ, continuous, and online monitoring of dissolved oxygen (DO) concentrations along various depths of lake water. The signal feedback mechanism was evaluated based on a relationship between voltage and DO concentration at corresponding depths. With an external resistance of 1000 Ω, a linear relationship was found (regression coefficient, R = 0. Read More

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http://dx.doi.org/10.1016/j.scitotenv.2019.04.032DOI Listing

Effect of fluorine substitution on sintering behaviour, mechanical and bioactivity of hydroxyapatite.

J Mech Behav Biomed Mater 2019 Apr 9;95:136-142. Epub 2019 Apr 9.

Bioceramics and Coating Division, CSIR-Central Glass & Ceramic Research Institute, 196 Raja S.C. Mullick Road, Kolkata 700032, India. Electronic address:

Fluorine substituted hydroxyapatite (FAp) with different degree of fluorine (F) substitution, has been synthesized using hydrothermal synthesis method. In the present work, as synthesized powders were consolidated by sintering at 1200 °C in air for 1 h. The sintered specimens were characterized using Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) for phase analysis. Read More

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http://dx.doi.org/10.1016/j.jmbbm.2019.03.032DOI Listing

Perylenequinone-based "turn on" fluorescent probe for hydrogen sulfide with high sensitivity in living cells.

Spectrochim Acta A Mol Biomol Spectrosc 2019 Mar 29;218:206-212. Epub 2019 Mar 29.

Key Laboratory of Optic-electric Sensing and Analytical Chemistry for Life Science, MOE, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China. Electronic address:

Hydrogen sulfide (HS) is a kind of gaseous signal molecule in many physiological processes. In order to detect HS, a novel "turn on" fluorescent probe 6,12-dihydroxyperylene-1,7-dione (DPD) was designed and synthesized. The probe DPD is fluorescence silence, while the addition of HS induces an obvious green fluorescence with an obvious color change from dark blue to yellow-green. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S13861425193036
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http://dx.doi.org/10.1016/j.saa.2019.03.112DOI Listing
March 2019
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Effect of differently methyl-substituted ionic liquids on Scenedesmus obliquus growth, photosynthesis, respiration, and ultrastructure.

Environ Pollut 2019 Apr 10;250:155-165. Epub 2019 Apr 10.

School of Environmental Science and Engineering, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310018, China. Electronic address:

Concerns have been raised regarding the ecotoxicity of ionic liquids (ILs) owing to their wide usage in numerous fields. Three imidazolium chloride ILs with different numbers of methyl substituents, 1-decyl-imidazolium chloride ([CIM]Cl), 1-decyl-3-methylimidazolium chloride ([CMIM]Cl), and 1-decyl-2,3-dimethylimidazolium chloride ([CDMIM]Cl), were examined to assess their effects on growth, photosynthesis pigments content, chlorophyll fluorescence, photosynthetic and respiration rate, and cellular ultrastructure of Scenedesmus obliquus. The results showed that algal growth was significantly inhibited by ILs treatments. Read More

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http://dx.doi.org/10.1016/j.envpol.2019.04.021DOI Listing

Four new guaiane sesquiterpenoids from agarwood of Aquilaria filaria.

Fitoterapia 2019 Apr 14. Epub 2019 Apr 14.

Key Laboratory of Biology and Genetic Resources of Tropical Crops, Ministry of Agriculture, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, PR China. Electronic address:

Six 8,12-epoxyguaiane sesquiterpenes (1-6), together with two known 2-(2-phenylethyl)chromone derivatives (7-8) were isolated from agarwood originating from Aquilaria filaria. Their structures were established by spectroscopic methods including IR, HRESIMS, 1D, and 2D NMR, and comparison with the published data. The absolute configuration of compound 1 was unambiguously determined by quantum chemical calculation of the electronic circular dichroism (ECD) spectrum. Read More

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http://dx.doi.org/10.1016/j.fitote.2019.04.007DOI Listing

Further terpenoids from Euphorbia tirucalli.

Fitoterapia 2019 Apr 14. Epub 2019 Apr 14.

BioCIS, Université Paris-Sud, CNRS, Université Paris-Saclay, 5 Rue J.-B. Clément, 92290 Châtenay-Malabry, France. Electronic address:

The phytochemical investigation of Euphorbia tirucalli L. (Euphorbiaceae) yielded four new compounds, including a rare cadalene-type sesquiterpene (tirucadalenone), two tirucallane triterpenoids, euphorol L and euphorol M, with the latter being described as an epimeric mixture, and a euphane triterpene, namely, euphorol N, together with 7 known compounds. Their structures and absolute configurations were elucidated from analysis of 1D (1H, J-modulated C) and 2D NMR (HSQC, HMBC and NOESY), high-resolution mass spectrometry (HRESIMS), optical rotation, and GIAO NMR shift calculation followed by CP3 analysis, along with comparison with literature reports. Read More

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http://dx.doi.org/10.1016/j.fitote.2019.04.001DOI Listing

An Extended Endoscopic Endonasal Approach for Sellar Area Chondrosarcoma: A Case Report and Literature Review.

World Neurosurg 2019 Apr 14. Epub 2019 Apr 14.

Department of Neurosurgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, People's Republic of China.

Background: Chondrosarcoma is a malignant tumor that originates from mesenchymal cells that have differentiated into chondrocytes, often growing laterally, rarely seen in the cranium, and seldom seen in the saddle area. We believe that only a few cases have been reported in the literature. We report a case of pituitary fossa chondrosarcoma, which was completely resected by an extended endoscopic endonasal approach, and a literature review. Read More

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http://dx.doi.org/10.1016/j.wneu.2019.04.075DOI Listing

Role of VE-Cadherin and p120-catenin in the formation of experimental intracranial aneurysms in animals.

World Neurosurg 2019 Apr 14. Epub 2019 Apr 14.

Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, China P.R. Electronic address:

Background: Dysfunction of endothelial cells (ECs) constitutes a critical factor in formatting intracranial aneurysms (IAs). However, little is known about the response of ECs to hemodynamic insults and its contribution to IA formation.

Methods And Material: IAs models were constructed in both adult female New Zealand white rabbits and male Sprague-Dawley rats. Read More

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http://dx.doi.org/10.1016/j.wneu.2019.04.077DOI Listing

Study on neuroendocrine-immune function of Phenylethanoid Glycosides of Desertliving Cistanche herb in perimenopausal rat model.

J Ethnopharmacol 2019 Apr 14:111884. Epub 2019 Apr 14.

Department of Pharmacology, Henan University of Chinese Medicine, Zhengzhou, 450008, China.

Ethnopharmacological Relevance: Desertliving Cistanche herb was first recorded in "Shen Nong'Herbal Classic" and listed as the top grade herbal medicine in it. Phenylethanoid glycosides are indicative components for identification and content determination of Desertliving Cistanche herb in Chinese pharmacopoeia, which is also one of the main active components. In this research, we explored the mechanism of phenylethanoid glycosides of Desertliving Cistanche herb to the perimenopausal model rats. Read More

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http://dx.doi.org/10.1016/j.jep.2019.111884DOI Listing

Cytotoxic effect of aqueous ethanolic extract of Luffa cylindrica leaves on cancer stem cells CD44/24 in breast cancer patients with various molecular sub-types using tissue samples in vitro.

J Ethnopharmacol 2019 Apr 14:111877. Epub 2019 Apr 14.

Medical Research Department, National Institute of Occupational Safety and Health, Egypt. Electronic address:

Ethnopharmacological Relevance: Luffa cylindrica (L.) M.Roem is a climbing plant its parts have been used as traditional medicine for the treatment of different types of diseases including diarrhea, inflammation, cancer and viral infections. Read More

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http://dx.doi.org/10.1016/j.jep.2019.111877DOI Listing

CREPT promotes glioma cell proliferation and invasion by activating Wnt/β-catenin pathway and is a novel target of microRNA-596.

Biochimie 2019 Apr 14. Epub 2019 Apr 14.

Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, 710038, Shaanxi Province, China. Electronic address:

Cell cycle-related and expression elevated protein in tumor (CREPT) is emerging as a novel cancer-related gene that is dysregulated in many kinds of malignancies. However, the expression and biological role of CREPT in glioma remains unclear. In the present study, we aimed to explore the potential function and regulation mechanism of CREPT in glioma. Read More

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http://dx.doi.org/10.1016/j.biochi.2019.04.014DOI Listing

Physiological roles of antisense RNAs in prokaryotes.

Biochimie 2019 Apr 14. Epub 2019 Apr 14.

CNRS UMR8261, IBPC, 13 Rue Pierre et Marie Curie, 75005, Paris, France. Electronic address:

Prokaryotes encounter constant and often brutal modifications to their environment. In order to survive, they need to maintain fitness, which includes adapting their protein expression patterns. Many factors control gene expression but this review focuses on just one, namely antisense RNAs (asRNAs), a class of non-coding RNAs (ncRNAs) characterized by their location in cis and their perfect complementarity with their targets. Read More

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http://dx.doi.org/10.1016/j.biochi.2019.04.015DOI Listing

Reactive oxygen species as mediators of oxygen signaling during fetal-to-neonatal circulatory transition.

Free Radic Biol Med 2019 Apr 14. Epub 2019 Apr 14.

Department of Pharmacology, School of Medicine, Universidad Complutense de Madrid, Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.

Reactive oxygen species (ROS) are frequently seen as pathological agents of oxidative stress. However, ROS are not always deleterious and can also act as cell signaling molecules. Vascular oxygen sensing and signaling during fetal-to-neonatal circulatory transition is a remarkable example of the physiological regulatory actions of ROS. Read More

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http://dx.doi.org/10.1016/j.freeradbiomed.2019.04.008DOI Listing

Abnormal cleavage and developmental arrest of human preimplantation embryos in vitro.

Eur J Med Genet 2019 Apr 14. Epub 2019 Apr 14.

The Evewell, 61 Harley Street, London, W1G 8QU, UK; School of Biosciences, University of Kent, Canterbury, CT2 7NJ, UK. Electronic address:

Despite improvements in culture conditions and laboratory techniques still only about 50% of human embryos reach the blastocyst stage of development in vitro. While many factors influence embryo development, aberrant cleavage divisions have only recently been shown to directly affect the genome in individual cells of human embryos resulting in chromosome loss, mosaicism and cell arrest. In this article we review the current literature in the area of aberrant cleavage in human embryos and its effect on blastocyst development. Read More

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http://dx.doi.org/10.1016/j.ejmg.2019.04.008DOI Listing

Clinical, immunologic, and molecular spectrum of patients with LPS-responsive beige-like anchor protein (LRBA) deficiency: a systematic review.

J Allergy Clin Immunol Pract 2019 Apr 14. Epub 2019 Apr 14.

Non-communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran. Electronic address:

Background: LPS-responsive beige-like anchor protein (LRBA) deficiency is a primary immunodeficiency and immune dysregulation syndrome caused by biallelic mutations in the LRBA gene. These mutations usually abrogate the protein expression of LRBA, leading to a broad spectrum of clinical phenotypes including autoimmunity, chronic diarrhea, hypogammaglobulinemia and recurrent infections.

Objective: Our aim was to systematically collect all studies reporting on the clinical manifestations, molecular and laboratory findings, and management of patients with LRBA deficiency. Read More

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http://dx.doi.org/10.1016/j.jaip.2019.04.011DOI Listing

Increasing Incidence of Colon Cancer in the Young: Assessing the Tumor Biology.

J Am Coll Surg 2019 Apr 14. Epub 2019 Apr 14.

Department of Surgery, University of Arizona, Tucson, AZ.

Background: Overall incidence of CC is decreasing, however with increasing early-onset colon cancer (EOCC <50 y.o.). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10727515193025
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http://dx.doi.org/10.1016/j.jamcollsurg.2019.03.022DOI Listing
April 2019
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Sensitization of Nociceptors and Dorsal Horn Neurons Contributes to Pain in Sickle Cell Disease.

Neurosci Lett 2019 Apr 14. Epub 2019 Apr 14.

Department of Diagnostic and Biological Sciences, University of Minnesota, School of Dentistry, Minneapolis, MN 55455, United States. Electronic address:

Sickle cell disease (SCD) describes a group of disorders associated with a point mutation in the beta chain of hemoglobin. The mutation leads to the creation of sickle hemoglobin (HbS) and causes distortion of erythrocytes through polymerization under low oxygen, resulting in characteristic sickle red blood cells. Vaso-occlusion episodes caused by accumulation of sRBCs results in ischemia-reperfusion injury, reduced oxygen supply to organs, oxidative stress, organ damage and severe pain that often requires hospitalization and opioid treatment. Read More

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http://dx.doi.org/10.1016/j.neulet.2019.04.013DOI Listing

Oleuropein aglycone and hydroxytyrosol interfere differently with toxic Aβ aggregation.

Food Chem Toxicol 2019 Apr 14. Epub 2019 Apr 14.

Department of Biomedical, Experimental and Clinical Sciences 'Mario Serio', University of Florence, Viale Morgagni 50 - 50134, Florence, Italy; Interuniversity Center for the Study of Neurodegenerative Diseases (CIMN), Florence, Italy. Electronic address:

Oleuropein aglycone (OleA), the most abundant polyphenol in extra virgin olive oil (EVOO), and Hydroxythyrosol (HT), the OleA main metabolite, have attracted our interest due to their multitarget effects, including the interference with amyloid aggregation path. However, the mechanistic details of their anti-amyloid effect are not known yet. We report here a broad biophysical approach and cell biology techniques that enabled us to characterize the different molecular mechanisms by which OleA and HT modulate the Aβ fibrillation, a main histopathological feature of Alzheimer's disease (AD). Read More

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http://dx.doi.org/10.1016/j.fct.2019.04.015DOI Listing

Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease.

Immunity 2019 Apr;50(4):992-1006

Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Roosevelt Drive, Oxford OX3 7FY, UK; Translational Gastroenterology Unit, Experimental Medicine Division, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address:

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. Cytokine-targeted therapies have transformed the treatment of IBD, providing control of symptoms and longer relapse-free periods. However, many patients fail to respond, highlighting the need for therapies tailored to the underlying cell and molecular disease drivers. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.017DOI Listing

Cytokine Circuits in Cardiovascular Disease.

Immunity 2019 Apr;50(4):941-954

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63139, USA. Electronic address:

Arterial inflammation is a hallmark of atherosclerosis, and appropriate management of this inflammation represents a major unmet therapeutic need for cardiovascular disease patients. Here, we review the diverse contributions of immune cells to atherosclerosis, the mechanisms of immune cell activation in this context, and the cytokine circuits that underlie disease progression. We discuss the recent application of these insights in the form of immunotherapy to treat cardiovascular disease and highlight how studies on the cardiovascular co-morbidity that arises in autoimmunity might reveal additional roles for cytokines in atherosclerosis. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613193012
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http://dx.doi.org/10.1016/j.immuni.2019.03.007DOI Listing
April 2019
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Transforming Growth Factor-β Signaling in Immunity and Cancer.

Immunity 2019 Apr;50(4):924-940

Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address:

Transforming growth factor (TGF)-β is a crucial enforcer of immune homeostasis and tolerance, inhibiting the expansion and function of many components of the immune system. Perturbations in TGF-β signaling underlie inflammatory diseases and promote tumor emergence. TGF-β is also central to immune suppression within the tumor microenvironment, and recent studies have revealed roles in tumor immune evasion and poor responses to cancer immunotherapy. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613193014
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http://dx.doi.org/10.1016/j.immuni.2019.03.024DOI Listing
April 2019
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The γ Family of Cytokines: Basic Biology to Therapeutic Ramifications.

Immunity 2019 Apr;50(4):832-850

Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Metabolic, and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1674, USA. Electronic address:

The common cytokine receptor γ chain, γ, is a component of the receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. Mutation of the gene encoding γ results in X-linked severe combined immunodeficiency in humans, and γ family cytokines collectively regulate development, proliferation, survival, and differentiation of immune cells. Here, we review the basic biology of these cytokines, highlighting mechanisms of signaling and gene regulation that have provided insights for immunodeficiency, autoimmunity, allergic diseases, and cancer. Read More

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http://dx.doi.org/10.1016/j.immuni.2019.03.028DOI Listing

An X-ray Vision for Phosphoantigen Recognition.

Immunity 2019 Apr;50(4):1026-1028

CRCM, Immunity and Cancer Team, Institut Paoli-Calmettes, INSERM, CNRS, Aix Marseille Université, Marseille, France.

Invariant Vγ9Vδ2 T cells respond to "phosphoantigen" metabolites through binding to the B30.2 domain of butyrophilin BTN3A. Yang et al. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S10747613193013
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http://dx.doi.org/10.1016/j.immuni.2019.03.015DOI Listing
April 2019
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Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells.

Cell Rep 2019 Apr;27(3):971-986.e9

Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada. Electronic address:

Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247193036
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http://dx.doi.org/10.1016/j.celrep.2019.03.047DOI Listing
April 2019
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A Comprehensive Drosophila melanogaster Transcription Factor Interactome.

Cell Rep 2019 Apr;27(3):955-970.e7

Department of Medicine, Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Systems Biology Graduate Program, Harvard University, Cambridge, MA 02138, USA; Bioinformatics and Integrative Genomics Ph.D. Program, Harvard University, Cambridge, MA 02138, USA; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address:

Combinatorial interactions among transcription factors (TFs) play essential roles in generating gene expression specificity and diversity in metazoans. Using yeast 2-hybrid (Y2H) assays on nearly all sequence-specific Drosophila TFs, we identified 1,983 protein-protein interactions (PPIs), more than doubling the number of currently known PPIs among Drosophila TFs. For quality assessment, we validated a subset of our interactions using MITOMI and bimolecular fluorescence complementation assays. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.071DOI Listing

Horizontal Boundary Cells, a Special Group of Somitic Cells, Play Crucial Roles in the Formation of Dorsoventral Compartments in Teleost Somite.

Cell Rep 2019 Apr;27(3):928-939.e4

Department of Biological Sciences, Graduate School of Science, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Electronic address:

Establishment of robust gene expression boundary is crucial for creating elaborate morphology during development. However, mechanisms underlying boundary formation have been extensively studied only in a few model systems. We examined the establishment of zic1/zic4-expression boundary demarcating dorsoventral boundary of the entire trunk of medaka fish (Oryzias latipes) and identified a subgroup of dermomyotomal cells called horizontal boundary cells (HBCs) as crucial players for the boundary formation. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.068DOI Listing

Quantitative Characterization of α-Synuclein Aggregation in Living Cells through Automated Microfluidics Feedback Control.

Cell Rep 2019 Apr;27(3):916-927.e5

Telethon Institute of Genetics and Medicine (TIGEM), Via Campi Flegrei 34, 80078 Pozzuoli (NA), Italy; Department of Chemical, Materials and Industrial Production Engineering, University of Naples Federico II, Piazzale Tecchio 80, 80125 Naples, Italy. Electronic address:

Aggregation of α-synuclein and formation of inclusions are hallmarks of Parkinson's disease (PD). Aggregate formation is affected by cellular environment, but it has been studied almost exclusively in cell-free systems. We quantitatively analyzed α-synuclein inclusion formation and clearance in a yeast cell model of PD expressing either wild-type (WT) α-synuclein or the disease-associated A53T mutant from the galactose (Gal)-inducible promoter. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.081DOI Listing

Essential Roles of Tbr1 in the Formation and Maintenance of the Orientation-Selective J-RGCs and a Group of OFF-Sustained RGCs in Mouse.

Cell Rep 2019 Apr;27(3):900-915.e5

Ruiz Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth), Houston, TX 77030, USA. Electronic address:

In the mouse retina, more than 30 retinal ganglion cell (RGC) subtypes have been classified based on a combined metric of morphological and functional characteristics. RGCs arise from a common pool of retinal progenitor cells during embryonic stages and differentiate into mature subtypes in adult retinas. However, the cellular and molecular mechanisms controlling formation and maturation of such remarkable cellular diversity remain unknown. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.077DOI Listing

The Exchangeable Apolipoprotein Nplp2 Sustains Lipid Flow and Heat Acclimation in Drosophila.

Cell Rep 2019 Apr;27(3):886-899.e6

Global Health Institute, School of Life Science, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address:

In ectotherms, increased ambient temperature requires the organism to consume substantial amounts of energy to sustain a higher metabolic rate, prevent cellular damage, and respond to heat stress. Here, we identify a heat-inducible apolipoprotein required for thermal acclimation in Drosophila. Neuropeptide-like precursor 2 (Nplp2) is an abundant hemolymphatic protein thought to be a neuropeptide. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247193040
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http://dx.doi.org/10.1016/j.celrep.2019.03.074DOI Listing
April 2019
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Parallel Processing of Sound Dynamics across Mouse Auditory Cortex via Spatially Patterned Thalamic Inputs and Distinct Areal Intracortical Circuits.

Cell Rep 2019 Apr;27(3):872-885.e7

Department of Biology, University of Maryland, College Park, MD 20742, USA; Program in Neuroscience and Cognitive Science, University of Maryland, College Park, MD 20742, USA. Electronic address:

Natural sounds have rich spectrotemporal dynamics. Spectral information is spatially represented in the auditory cortex (ACX) via large-scale maps. However, the representation of temporal information, e. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.069DOI Listing

Overlapping Activities of Two Neuronal Splicing Factors Switch the GABA Effect from Excitatory to Inhibitory by Regulating REST.

Cell Rep 2019 Apr;27(3):860-871.e8

Department of Anatomy and Cell Biology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Inflammation Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Otolaryngology-Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA; Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. Electronic address:

A truncating mutation in the mouse Srrm4 gene, which encodes a neuronal splicing factor, causes alternative splicing defects selectively in the ear. The mechanism by which splicing is preserved in the brain of these mice is not known. Here, we show that SRRM3 limits the Srrm4 mutation-associated defects to the ear and that, in cortical neurons, overlapping SRRM3-SRRM4 activity regulates the development of interneuronal inhibition. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.072DOI Listing

Functional Network Analysis Reveals the Relevance of SKIIP in the Regulation of Alternative Splicing by p38 SAPK.

Cell Rep 2019 Apr;27(3):847-859.e6

Cell Signaling Research Group, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain; Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac, 10, 08028 Barcelona, Spain. Electronic address:

Alternative splicing is a prevalent mechanism of gene regulation that is modulated in response to a wide range of extracellular stimuli. Stress-activated protein kinases (SAPKs) play a key role in controlling several steps of mRNA biogenesis. Here, we show that osmostress has an impact on the regulation of alternative splicing (AS), which is partly mediated through the action of p38 SAPK. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.060DOI Listing

IL-38 Ameliorates Skin Inflammation and Limits IL-17 Production from γδ T Cells.

Cell Rep 2019 Apr;27(3):835-846.e5

Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany. Electronic address:

Interleukin-38 (IL-38) is a cytokine of the IL-1 family with a role in chronic inflammation. However, its main cellular targets and receptors remain obscure. IL-38 is highly expressed in the skin and downregulated in psoriasis patients. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S22111247193042
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http://dx.doi.org/10.1016/j.celrep.2019.03.082DOI Listing
April 2019
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Lethal Poisoning of Cancer Cells by Respiratory Chain Inhibition plus Dimethyl α-Ketoglutarate.

Cell Rep 2019 Apr;27(3):820-834.e9

Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, Equipe 11 labellisée par la Ligue contre le Cancer, 75006 Paris, France; Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France. Electronic address:

Inhibition of oxidative phosphorylation (OXPHOS) by 1-cyclopropyl-4-(4-[(5-methyl-3-(3-[4-(trifluoromethoxy)phenyl]-1,2,4-oxadiazol-5-yl)-1H-pyrazol-1-yl)methyl]pyridin-2-yl)piperazine (BAY87-2243, abbreviated as B87), a complex I inhibitor, fails to kill human cancer cells in vitro. Driven by this consideration, we attempted to identify agents that engage in synthetically lethal interactions with B87. Here, we report that dimethyl α-ketoglutarate (DMKG), a cell-permeable precursor of α-ketoglutarate that lacks toxicity on its own, kills cancer cells when combined with B87 or other inhibitors of OXPHOS. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.058DOI Listing

Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.

Cell Rep 2019 Apr;27(3):806-819.e5

Ludwig Collaborative and Swim Across America Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Weill Cornell Medicine, New York, NY 10065, USA. Electronic address:

KRAS is one of the driver oncogenes in non-small-cell lung cancer (NSCLC) but remains refractory to current modalities of targeted pathway inhibition, which include inhibiting downstream kinase MEK to circumvent KRAS activation. Here, we show that pulsatile, rather than continuous, treatment with MEK inhibitors (MEKis) maintains T cell activation and enables their proliferation. Two MEKis, selumetinib and trametinib, induce T cell activation with increased CTLA-4 expression and, to a lesser extent, PD-1 expression on T cells in vivo after cyclical pulsatile MEKi treatment. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.066DOI Listing

PAR2-Mediated cAMP Generation Suppresses TRPV4-Dependent Ca Signaling in Alveolar Macrophages to Resolve TLR4-Induced Inflammation.

Cell Rep 2019 Apr;27(3):793-805.e4

Department of Pharmacology and Centre for Lung and Vascular Biology, University of Illinois, College of Medicine, Chicago, IL, USA. Electronic address:

Alveolar macrophages (AMs), upon sensing pathogens, trigger host defense by activating toll-like receptor 4 (TLR4), but the counterbalancing mechanisms that deactivate AM inflammatory signaling and prevent lethal edema, the hallmark of acute lung injury (ALI), remain unknown. Here, we demonstrate the essential role of AM protease-activating receptor 2 (PAR2) in rapidly suppressing inflammation to prevent long-lasting injury. We show that thrombin, released during TLR4-induced lung injury, directly activates PAR2 to generate cAMP, which abolishes Ca entry through the TRPV4 channel. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.053DOI Listing

The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.

Cell Rep 2019 Apr;27(3):776-792.e7

Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA; Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA. Electronic address:

Many viruses shut off host gene expression to inhibit antiviral responses. Viral proteins and host proteins required for viral replication are typically spared in this process, but the mechanisms of target selectivity during host shutoff remain poorly understood. Using transcriptome-wide and targeted reporter experiments, we demonstrate that the influenza A virus endoribonuclease PA-X usurps RNA splicing to selectively target host RNAs for destruction. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.063DOI Listing

CD89 Is a Potent Innate Receptor for Bacteria and Mediates Host Protection from Sepsis.

Cell Rep 2019 Apr;27(3):762-775.e5

INSERM U1149, Centre de Recherche sur l'Inflammation, Paris, France; CNRS ERL8252, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Faculté de Médecine, Site Xavier Bichat, Paris, France; Inflamex Laboratory of Excellence, Paris, France. Electronic address:

Direct bacterial recognition by innate receptors is crucial for bacterial clearance. Here, we show that the IgA receptor CD89 is a major innate receptor that directly binds bacteria independently of its cognate ligands IgA and c-reactive protein (CRP). This binding is only partially inhibited by serum IgA and induces bacterial phagocytosis by CD11c dendritic cells and monocytes and/or macrophages, suggesting a physiological role in innate host defense. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.062DOI Listing

Butyrate Protects Mice from Clostridium difficile-Induced Colitis through an HIF-1-Dependent Mechanism.

Cell Rep 2019 Apr;27(3):750-761.e7

Laboratory of Immunoinflammation, Department of Genetics, Evolution, Microbiology, and Immunology, Institute of Biology, University of Campinas, Campinas, SP 13083-862, Brazil. Electronic address:

Antibiotic-induced dysbiosis is a key factor predisposing intestinal infection by Clostridium difficile. Here, we show that interventions that restore butyrate intestinal levels mitigate clinical and pathological features of C. difficile-induced colitis. Read More

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http://dx.doi.org/10.1016/j.celrep.2019.03.054DOI Listing
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