129 results match your criteria ntd indicating


Prevention of Neural Tube Defects in Europe: A Public Health Failure.

Front Pediatr 2021 24;9:647038. Epub 2021 Jun 24.

Department of Genetics, Eurocat Northern Netherlands, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.

Thirty years ago it was demonstrated that folic acid taken before pregnancy and in early pregnancy reduced the risk of a neural tube defect (NTD). Despite Public Health Initiatives across Europe recommending that women take 0.4 mg folic acid before becoming pregnant and during the first trimester, the prevalence of NTD pregnancies has not materially decreased in the EU since 1998, in contrast to the dramatic fall observed in the USA. Read More

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Structure dictates the mechanism of ligand recognition in the histidine and maltose binding proteins.

Curr Res Struct Biol 2020 17;2:180-190. Epub 2020 Aug 17.

Simons Centre for the Study of Living Machines, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India.

Two mechanisms, induced fit (IF) and conformational selection (CS), have been proposed to explain ligand recognition coupled conformational changes. The histidine binding protein (HisJ) adopts the CS mechanism, in which a pre-equilibrium is established between the open and the closed states with the ligand binding to the closed state. Despite being structurally similar to HisJ, the maltose binding protein (MBP) adopts the IF mechanism, in which the ligand binds the open state and induces a transition to the closed state. Read More

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More Is Always Better Than One: The N-Terminal Domain of the Spike Protein as Another Emerging Target for Hampering the SARS-CoV-2 Attachment to Host Cells.

Int J Mol Sci 2021 Jun 16;22(12). Epub 2021 Jun 16.

Institute of Crystallography, CNR, 70126 Bari, Italy.

Although the approved vaccines are proving to be of utmost importance in containing the Coronavirus disease 2019 (COVID-19) threat, they will hardly be resolutive as new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, a single-stranded RNA virus) variants might be insensitive to the immune response they induce. In this scenario, developing an effective therapy is still a dire need. Different targets for therapeutic antibodies and diagnostics have been identified, among which the SARS-CoV-2 spike (S) glycoprotein, particularly its receptor-binding domain, has been defined as crucial. Read More

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Humoral immune response to circulating SARS-CoV-2 variants elicited by inactivated and RBD-subunit vaccines.

Cell Res 2021 07 21;31(7):732-741. Epub 2021 May 21.

School of Pharmaceutical Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, China.

SARS-CoV-2 variants could induce immune escape by mutations on the receptor-binding domain (RBD) and N-terminal domain (NTD). Here we report the humoral immune response to circulating SARS-CoV-2 variants, such as 501Y.V2 (B. Read More

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Metformin leads to accumulation of reactive oxygen species by inhibiting the NFE2L1 expression in human hepatocellular carcinoma cells.

Toxicol Appl Pharmacol 2021 06 8;420:115523. Epub 2021 Apr 8.

School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China; School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China. Electronic address:

Metformin, as the first-line drug for the treatment of type 2 diabetes mellitus, has been shown to possess a capability to activate or inhibit the production of reactive oxygen species (ROS) in different ways. However, the detailed mechanisms of the opposite effect are poorly understood. Here we provide evidence that metformin induces accumulation of ROS by inhibiting the expression of a core antioxidant transcription factor nuclear factor erythroid 2 like 1 (NFE2L1/Nrf1) in human hepatocellular carcinoma HepG2 cells. Read More

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N-terminal domain regulates steroid activation of elephant shark glucocorticoid and mineralocorticoid receptors.

J Steroid Biochem Mol Biol 2021 Jun 27;210:105845. Epub 2021 Feb 27.

Division of Nephrology-Hypertension, Department of Medicine, University of California, San Diego, CA, USA. Electronic address:

Orthologs of human glucocorticoid receptor (GR) and human mineralocorticoid receptor (MR) first appear in cartilaginous fishes. Subsequently, the MR and GR diverged to respond to different steroids: the MR to aldosterone and the GR to cortisol and corticosterone. We report that cortisol, corticosterone and aldosterone activate full-length elephant shark GR, and progesterone, which activates elephant shark MR, does not activate elephant shark GR. Read More

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Inadequate Status and Low Awareness of Folate in Switzerland-A Call to Strengthen Public Health Measures to Ensure Sufficient Intakes.

Nutrients 2020 Dec 3;12(12). Epub 2020 Dec 3.

Institute of Food and Beverage Innovation, ZHAW School of Life Sciences and Facility Management, Einsiedlerstrasse 34, 8820 Waedenswil, Switzerland.

Background: Folate plays an essential role in the prevention of neural tube defects, yet little is known about the folate status of women of reproductive age or to what degree the general population is aware of the importance of folate in early-life development. We aimed to determine folate status in women of reproductive age and pregnant women in Switzerland, and to assess folate awareness in the Swiss population.

Methods: In a convenience sample of 171 women of reproductive age and 177 pregnant women throughout Switzerland, we measured red blood cell (RBC) folate concentration. Read More

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December 2020

Photodynamic effect of palladium porphyrin derived from cashew nut shell liquid against promastigote forms of Leishmania braziliensis.

Photodiagnosis Photodyn Ther 2021 Mar 4;33:102083. Epub 2020 Nov 4.

Laboratory of Products and Process Technology (LPT), Federal University of Ceará (UFC), Campus do Pici 60455-900, Fortaleza, Ceara, Brazil.

Cutaneous leishmaniasis (CL) is a neglected tropical disease (NTD), endemic mainly in low-income countries that lack adequate basic health care. The emergence of resistant parasites to pentavalent antimonials has led to the search for new treatments for CL. Photodynamic therapy (PDT) is a promising non-invasive and less toxic alternative for the treatment of CL. Read More

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Genetic Diversity of in Qena Governorate, Upper Egypt.

Infect Drug Resist 2020 15;13:3601-3611. Epub 2020 Oct 15.

Department of Medical Parasitology, Faculty of Medicine, Assiut University, Assiut, Egypt.

Introduction: Schistosomiasis is an important neglected tropical disease (NTD) in several developing countries. Praziquantel is the principle and efficacious chemotherapeutic agent that has been used to treat schistosomiasis for decades. Unfortunately, emerging resistance to praziquantel with accompanying reduced efficacy is reported in some localities. Read More

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October 2020

Hesperetin targets the hydrophobic pocket of the nucleoprotein/phosphoprotein binding site of human respiratory syncytial virus.

J Biomol Struct Dyn 2020 Oct 20:1-13. Epub 2020 Oct 20.

Multiuser Center for Biomolecular Innovation (CMIB), Instituto de Biociências, Letras e Ciências Exatas, UNESP, São José do Rio Preto, CEP, SP, Brazil.

The human Respiratory Syncytial Virus (hRSV) is one of the most common causes of acute respiratory diseases such as bronchiolitis and pneumonia in children worldwide. Among the viral proteins, the nucleoprotein (N) stands out for forming the nucleocapsid (NC) that functions as a template for replication and transcription by the viral polymerase complex. The NC/polymerase recognition is mediated by the phosphoprotein (P), which establishes an interaction of its C-terminal residues with a hydrophobic pocket in the N-terminal domain of N (N-NTD). Read More

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October 2020

Structures of the SARS-CoV-2 nucleocapsid and their perspectives for drug design.

EMBO J 2020 10 11;39(20):e105938. Epub 2020 Sep 11.

Research Network of Immunity and Health (RNIH), Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.

COVID-19, caused by SARS-CoV-2, has resulted in severe and unprecedented economic and social disruptions in the world. Nucleocapsid (N) protein, which is the major structural component of the virion and is involved in viral replication, assembly and immune regulation, plays key roles in the viral life cycle. Here, we solved the crystal structures of the N- and C-terminal domains (N-NTD and N-CTD) of SARS-CoV-2 N protein, at 1. Read More

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October 2020

-Terminus Does Not Govern Protein Turnover of CENP-A.

Int J Mol Sci 2020 Aug 26;21(17). Epub 2020 Aug 26.

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore.

Centromere integrity underlies an essential framework for precise chromosome segregation and epigenetic inheritance. Although centromeric DNA sequences vary among different organisms, all eukaryotic centromeres comprise a centromere-specific histone H3 variant, centromeric protein A (CENP-A), on which other centromeric proteins assemble into the kinetochore complex. This complex connects chromosomes to mitotic spindle microtubules to ensure accurate partitioning of the genome into daughter cells. Read More

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Combination therapy with androgen receptor N-terminal domain antagonist EPI-7170 and enzalutamide yields synergistic activity in AR-V7-positive prostate cancer.

Mol Oncol 2020 10 9;14(10):2455-2470. Epub 2020 Aug 9.

Genome Sciences Centre, BC Cancer, Vancouver, BC, Canada.

Resistance of castration-resistant prostate cancer (CRPC) to enzalutamide and abiraterone involves the expression of constitutively active, truncated androgen receptor (AR) splice variants (AR-Vs) that lack a C-terminal ligand-binding domain (LBD). Both full-length AR and truncated AR-Vs require a functional N-terminal domain (NTD) for transcriptional activity thereby providing rationale for the development of ralaniten (EPI-002) as a first-in-class antagonist of the AR-NTD. Here, we evaluated the antitumor effect of a next-generation analog of ralaniten (EPI-7170) as a monotherapy or in combination with enzalutamide in prostate cancer cells that express AR-V7 that were resistant to enzalutamide. Read More

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October 2020

Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike.

Nature 2020 08 22;584(7821):450-456. Epub 2020 Jul 22.

Aaron Diamond AIDS Research Center, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic continues, with devasting consequences for human lives and the global economy. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this coronavirus. Here we report the isolation of sixty-one SARS-CoV-2-neutralizing monoclonal antibodies from five patients infected with SARS-CoV-2 and admitted to hospital with severe coronavirus disease 2019 (COVID-19). Read More

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Potent Neutralizing Monoclonal Antibodies Directed to Multiple Epitopes on the SARS-CoV-2 Spike.

bioRxiv 2020 Jun 18. Epub 2020 Jun 18.

The SARS-CoV-2 pandemic rages on with devasting consequences on human lives and the global economy. The discovery and development of virus-neutralizing monoclonal antibodies could be one approach to treat or prevent infection by this novel coronavirus. Here we report the isolation of 61 SARS-CoV-2-neutralizing monoclonal antibodies from 5 infected patients hospitalized with severe disease. Read More

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Recent molecular insights into canonical pre-mRNA 3'-end processing.

Transcription 2020 04 11;11(2):83-96. Epub 2020 Jun 11.

Department of Biological Sciences, Columbia University , New York, NY, USA.

The majority of eukaryotic messenger RNA precursors (pre-mRNAs) undergo cleavage and polyadenylation at their 3' end. This canonical 3'-end processing depends on sequence elements in the pre-mRNA as well as a mega-dalton protein machinery. The cleavage site in mammalian pre-mRNAs is located between an upstream poly(A) signal, most frequently an AAUAAA hexamer, and a GU-rich downstream sequence element. Read More

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Association between body mass index and folate insufficiency indicative of neural tube defects risk among nonpregnant women of childbearing age in the United States, NHANES, 2007-2010.

Birth Defects Res 2020 04 13;112(6):490-502. Epub 2020 Feb 13.

Department of Epidemiology, Rollins School of Public Health of Emory University, Atlanta, Georgia.

Background: Maternal folate status and obesity are known risk factors for neural tube defects (NTD) in the offspring. We examined the association between body mass index (BMI) categories and blood folate concentrations, specifically, red blood cell (RBC) folate concentrations indicative of NTD risk among nonpregnant women of child-bearing age (20-44 years) in the United States.

Methods: We used data from 2007 to 2010 US National Health and Nutrition Examination Survey (NHANES). Read More

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Identification and molecular analysis of interaction sites in the MtSEO-F1 protein involved in forisome assembly.

Int J Biol Macromol 2020 Feb 13;144:603-614. Epub 2019 Dec 13.

Institute for Plant Biology and Biotechnology, University of Münster, Schlossplatz 8, 48143 Münster, Germany; Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Schlossplatz 8, 48143 Münster, Germany. Electronic address:

Forisomes are large mechanoprotein complexes found solely in legumes such as Medicago truncatula. They comprise several "sieve element occlusion by forisome" (SEO-F) subunits, with MtSEO-F1 as the major structure-forming component. SEO-F proteins possess three conserved domains -an N-terminal domain (SEO-NTD), a potential thioredoxin fold, and a C-terminal domain (SEO-CTD)- but structural and biochemical data are scarce and little is known about the contribution of these domains to forisome assembly. Read More

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February 2020

The N-terminal 1-55 residues domain of pyruvate dehydrogenase from Escherichia coli assembles as a dimer in solution.

Protein Eng Des Sel 2019 12;32(6):271-276

College of Chemistry and Pharmacy, Northwest A&F University, Yangling, China.

The pyruvate dehydrogenase complex (PDHc) from Escherichia coli is a large protein complex consisting of multiple copies of the pyruvate dehydrogenase (E1ec), dihydrolipoamide acetyltransferase (E2ec) and dihydrolipoamide dehydrogenase (E3ec). The N-terminal domain (NTD, residues 1-55) of E1ec plays a critical role in the interaction between E1ec and E2ec and the whole PDHc activity. Using circular dichroism, size-exclusion chromatography and dynamic light scattering spectroscopy, we show that the NTD of E1ec presents dimeric assembly under physiological condition. Read More

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December 2019

Identification of the immunodominant neutralizing regions in the spike glycoprotein of porcine deltacoronavirus.

Virus Res 2020 01 6;276:197834. Epub 2019 Dec 6.

Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, 611130, China; Sichuan Science-Observation Experimental Station for Veterinary Drugs and Veterinary Diagnostic Technology, Ministry of Agriculture, Chengdu, 611130, China; National Animal Experiment Teaching Demonstration Center, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address:

Porcine deltacoronavirus (PDCoV), is an emerging enteropathogenic coronavirus in pigs, that poses a novel threat to swine husbandry worldwide. Crucial to halting PDCoV transmission and infection is the development of effective therapies and vaccines. The spike (S) protein of coronavirus is the major target of host neutralizing antibodies, however the immunodominant neutralizing region in the S protein of PDCoV has not been defined. Read More

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January 2020

Neto proteins regulate gating of the kainate-type glutamate receptor GluK2 through two binding sites.

J Biol Chem 2019 11 18;294(47):17889-17902. Epub 2019 Oct 18.

State Key Laboratory of Pharmaceutical Biotechnology, Department of Neurology, Affiliated Drum Tower Hospital of Nanjing University Medical School, and Ministry of Education Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing 210032, China

The neuropilin and tolloid-like (Neto) proteins Neto1 and Neto2 are auxiliary subunits of kainate-type glutamate receptors (KARs) that regulate KAR trafficking and gating. However, how Netos bind and regulate the biophysical functions of KARs remains unclear. Here, we found that the N-terminal domain (NTD) of glutamate receptor ionotropic kainate 2 (GluK2) binds the first complement C1r/C1s-Uegf-BMP (CUB) domain of Neto proteins ( NTD-CUB1 interaction) and that the core of GluK2 (GluK2ΔNTD) binds Netos through domains other than CUB1s (core-Neto interaction). Read More

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November 2019

Phospho-Ser727 triggers a multistep inactivation of STAT3 by rapid dissociation of pY705-SH2 through C-terminal tail modulation.

Int Immunol 2020 02;32(2):73-88

Department of Immunology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Signal transducer and activator of transcription 3 (STAT3) is involved in many biological processes, including immunity and cancer. STAT3 becomes phosphorylated at Tyr705 and Ser727 on IL-6 stimulation. Phospho-Tyr705 (pY705) stabilizes the STAT3 dimer with reciprocal interactions between pY705 and the SH2 of the other molecule and phospho-Ser727 (pS727) accelerates pY705 dephosphorylation. Read More

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February 2020

Intramolecular Interactions Dominate the Autoregulation of Stringent Factor RelA.

Front Microbiol 2019 27;10:1966. Epub 2019 Aug 27.

Centre for Bacterial Stress Response and Persistence, Department of Biology, University of Copenhagen, Copenhagen, Denmark.

Amino acid starvation in activates the enzymatic activity of the stringent factor RelA, leading to accumulation of the alarmone nucleotide (p)ppGpp. The alarmone acts as an intercellular messenger to regulate transcription, translation and metabolism to mediate bacterial stress adaptation. The enzymatic activity of RelA is subject to multi-layered allosteric control executed both by ligands - such as "starved" ribosomal complexes, deacylated tRNA and pppGpp - and by individual RelA domains. Read More

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Glycine 29 Is Critical for Conformational Changes of the Spike Glycoprotein of Mouse Hepatitis Virus A59 Triggered by either Receptor Binding or High pH.

J Virol 2019 10 30;93(20). Epub 2019 Sep 30.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Mouse hepatitis virus (MHV) uses its N-terminal domain (NTD) of the viral spike (S) protein to bind the host receptor mouse carcinoembryonic antigen-related cell adhesion molecule 1a (mCEACAM1a) and mediate virus entry. Our previous crystal structure study of the MHV NTD/mCEACAM1a complex (G. Peng, D. Read More

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October 2019

ADAMTS Sol narae cleaves extracellular Wingless to generate a novel active form that regulates cell proliferation in Drosophila.

Cell Death Dis 2019 07 22;10(8):564. Epub 2019 Jul 22.

Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon, Korea.

Wnt/ Wingless (Wg) is essential for embryonic development and adult homeostasis in all metazoans, but the mechanisms by which secreted Wnt/Wg is processed remain largely unknown. A Drosophila Sol narae (Sona) is a member of A Disintegrin And Metalloprotease with ThromboSpondin motif (ADAMTS) family, and positively regulates Wg signaling by promoting Wg secretion. Here we report that Sona and Wg are secreted by both conventional Golgi and exosomal transports, and Sona cleaves extracellular Wg at the two specific sites, leading to the generation of N-terminal domain (NTD) and C-terminal domain (CTD) fragments. Read More

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A unified mechanism for LLPS of ALS/FTLD-causing FUS as well as its modulation by ATP and oligonucleic acids.

PLoS Biol 2019 06 12;17(6):e3000327. Epub 2019 Jun 12.

Department of Biological Sciences, Faculty of Science, National University of Singapore, Singapore.

526-residue Fused in sarcoma (FUS) undergoes liquid-liquid phase separation (LLPS) for its functions, which can further transit into pathological aggregation. ATP and nucleic acids, the universal cellular actors, were shown to modulate LLPS of FUS in a unique manner: enhancement and then dissolution. Currently, the driving force for LLPS of FUS is still under debate, while the mechanism for the modulation remains completely undefined. Read More

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A novel nipple-areola complex involvement predictive index for indicating nipple-sparing mastectomy in breast cancer patients.

Breast Cancer 2019 Nov 8;26(6):808-816. Epub 2019 Jun 8.

Department of Surgery, Teikyo University School of Medicine, Tokyo, 173-8606, Japan.

Background: Nipple-sparing mastectomy (NSM) is increasingly used in breast cancer patients, as it offers better cosmetic outcomes and improves quality of life. Nipple-areola complex (NAC) involvement must be accurately determined to identify which patients may be candidates for NSM. We aimed to identify the predictors of NAC involvement and develop a clinical predictive model to determine the patients for whom NAC preservation may be considered. Read More

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November 2019

Genetic evolution analysis and pathogenicity assessment of porcine epidemic diarrhea virus strains circulating in part of China during 2011-2017.

Infect Genet Evol 2019 04 21;69:153-165. Epub 2019 Jan 21.

Department of Swine Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, China. Electronic address:

In recent years, the outbreaks of porcine epidemic diarrhea (PED) caused by the highly virulent porcine epidemic diarrhea virus (PEDV) variants occurred frequently in China, resulting in severe economic impacts to the pork industry. In this study, we selected and analyzed the genetic evolution of 15 PEDV representative strains that were identified in fecal samples of diarrheic piglets in 10 provinces and cities during 2011-2017. The phylogenetic analysis indicated that all the 15 PEDV isolates clustered into G2 genotype associated with the current circulating strains. Read More

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Removal of steroid hormones and biocides from rural wastewater by an integrated constructed wetland.

Sci Total Environ 2019 Apr 7;660:358-365. Epub 2019 Jan 7.

The Environmental Research Institute, MOE Key Laboratory of Environmental Theoretical Chemistry, South China Normal University, Guangzhou 510006, China. Electronic address:

Steroid hormones and biocides are regarded as emerging contaminants in rural wastewater in China, owing to their widespread occurrence and adverse effects on both aquatic organisms and humans. Constructed wetlands (CWs) are an alternative technology for cost-effective and efficient decentralized rural sewage treatment. In this study, an integrated constructed wetland (ICW) system was built and used to treat a typical rural wastewater mixture composed of domestic sewage and livestock wastewater from a small village. Read More

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Lysosomal cholesterol export reconstituted from fragments of Niemann-Pick C1.

Elife 2018 07 26;7. Epub 2018 Jul 26.

Departments of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, United States.

Niemann-Pick C1 (NPC1) is a polytopic membrane protein with 13 transmembrane helices that exports LDL-derived cholesterol from lysosomes by carrying it through the 80 Å glycocalyx and the 40 Å lipid bilayer. Transport begins when cholesterol binds to the N-terminal domain (NTD) of NPC1, which projects to the surface of the glycocalyx. Here, we reconstitute cholesterol transport by expressing the NTD as a fragment separate from the remaining portion of NPC1. Read More

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