5,646 results match your criteria screens identified

The cytokine FAM3B/PANDER is an FGFR ligand that promotes posterior development in .

Proc Natl Acad Sci U S A 2021 May;118(20)

Institute of Neuroscience, Translational Medicine Institute, Health Science Center, Xi'an Jiaotong University, 710061 Xi'an, China;

Fibroblast growth factor (FGF)/extracellular signal-regulated kinase (ERK) signaling plays a crucial role in anterior-posterior (A-P) axial patterning of vertebrate embryos by promoting posterior development. In our screens for novel developmental regulators in embryos, we identified Fam3b as a secreted factor regulated in ectodermal explants. Family with sequence similarity 3 member B (FAM3B)/PANDER (pancreatic-derived factor) is a cytokine involved in glucose metabolism, type 2 diabetes, and cancer in mammals. Read More

View Article and Full-Text PDF

Biomechanical regulation of breast cancer metastasis and progression.

Sci Rep 2021 May 10;11(1):9838. Epub 2021 May 10.

Department of Biomedical Engineering, University of Texas at Austin, 1 University Station, BME 5.202D, C0800, Austin, TX, 78712, USA.

Physical activity has been consistently linked to decreased incidence of breast cancer and a substantial increase in the length of survival of patients with breast cancer. However, the understanding of how applied physical forces directly regulate breast cancer remains limited. We investigated the role of mechanical forces in altering the chemoresistance, proliferation and metastasis of breast cancer cells. Read More

View Article and Full-Text PDF

Exploiting the HSP60/10 chaperonin system as a chemotherapeutic target for colorectal cancer.

Bioorg Med Chem 2021 Apr 19;40:116129. Epub 2021 Apr 19.

Indiana University School of Medicine, Department of Biochemistry and Molecular Biology, 635 Barnhill Dr., Indianapolis, IN 46202, United States. Electronic address:

Over the past few decades, an increasing variety of molecular chaperones have been investigated for their role in tumorigenesis and as potential chemotherapeutic targets; however, the 60 kDa Heat Shock Protein (HSP60), along with its HSP10 co-chaperone, have received little attention in this regard. In the present study, we investigated two series of our previously developed inhibitors of the bacterial homolog of HSP60/10, called GroEL/ES, for their selective cytotoxicity to cancerous over non-cancerous colorectal cells. We further developed a third "hybrid" series of analogs to identify new candidates with superior properties than the two parent scaffolds. Read More

View Article and Full-Text PDF

Lrp5 mutant and crispant zebrafish faithfully model human osteoporosis, establishing the zebrafish as a platform for CRISPR-based functional screening of osteoporosis candidate genes.

J Bone Miner Res 2021 May 6. Epub 2021 May 6.

Center for Medical Genetics Ghent, Department of Biomolecular Medicine, Ghent University, Ghent, Belgium.

Genome-wide association studies (GWAS) have improved our understanding of the genetic architecture of common, complex diseases such as osteoporosis. Nevertheless, to attribute functional skeletal contributions of candidate genes to osteoporosis-related traits there is a need for efficient and cost-effective in vivo functional testing. This can be achieved through CRISPR-based reverse genetic screens, where phenotyping is traditionally performed in stable germline KO mutants. Read More

View Article and Full-Text PDF

A Solid Supported Membrane-Based Technology for Electrophysical Screening of BAT1-Modulating Compounds.

SLAS Discov 2021 May 6:24725552211011180. Epub 2021 May 6.

In Vitro Biology & High-throughput Chemistry, Integrated Drug Discovery, Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany.

Classical high-throughput screening (HTS) technologies for the analysis of ionic currents across biological membranes can be performed using fluorescence-based, radioactive, and mass spectrometry (MS)-based uptake assays. These assays provide rapid results for pharmacological HTS, but the underlying, indirect analytical character of these assays can be linked to high false-positive hit rates. Thus, orthogonal and secondary assays using more biological target-based technologies are indispensable for further compound validation and optimization. Read More

View Article and Full-Text PDF

Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity.

Nature 2021 May 5. Epub 2021 May 5.

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape. Read More

View Article and Full-Text PDF

Co-occupancy identifies transcription factor co-operation for axon growth.

Nat Commun 2021 05 5;12(1):2555. Epub 2021 May 5.

Department of Biomedical Sciences, Marquette University, Milwaukee, WI, USA.

Transcription factors (TFs) act as powerful levers to regulate neural physiology and can be targeted to improve cellular responses to injury or disease. Because TFs often depend on cooperative activity, a major challenge is to identify and deploy optimal sets. Here we developed a bioinformatics pipeline, centered on TF co-occupancy of regulatory DNA, and used it to predict factors that potentiate the effects of pro-regenerative Klf6 in vitro. Read More

View Article and Full-Text PDF

Comprehensive CRISPR-Cas9 screens identify genetic determinants of drug responsiveness in multiple myeloma.

Blood Adv 2021 May;5(9):2391-2402

Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany.

The introduction of new drugs in the past years has substantially improved outcome in multiple myeloma (MM). However, the majority of patients eventually relapse and become resistant to one or multiple drugs. While the genetic landscape of relapsed/ resistant multiple myeloma has been elucidated, the causal relationship between relapse-specific gene mutations and the sensitivity to a given drug in MM has not systematically been evaluated. Read More

View Article and Full-Text PDF

High-Throughput Approaches for the Identification of Antivirulents.

mBio 2021 05 4;12(3). Epub 2021 May 4.

Department of Biosciences, Rice University, Houston, Texas, USA

Antimicrobial resistance is a serious medical threat, particularly given the decreasing rate of discovery of new treatments. Although attempts to find new treatments continue, it has become clear that merely discovering new antimicrobials, even if they are new classes, will be insufficient. It is essential that new strategies be aggressively pursued. Read More

View Article and Full-Text PDF

Family Food Environment during the COVID-19 Pandemic: A Qualitative Study.

Children (Basel) 2021 Apr 29;8(5). Epub 2021 Apr 29.

Department of Child and Family Science, California State University, Fresno, CA 93740, USA.

Background: The COVID-19 pandemic, with its cyclical lockdown restrictions and school closures, has influenced family life. The home, work, and school environments have collided and merged to form a new normal for many families. This merging extends into the family food environment, and little is known about how families are currently navigating this landscape. Read More

View Article and Full-Text PDF

The Gut-Brain-Microbiome Axis and Its Link to Autism: Emerging Insights and the Potential of Zebrafish Models.

Front Cell Dev Biol 2021 15;9:662916. Epub 2021 Apr 15.

Department of Biology, University of Miami, Coral Gables, FL, United States.

Research involving autism spectrum disorder (ASD) most frequently focuses on its key diagnostic criteria: restricted interests and repetitive behaviors, altered sensory perception, and communication impairments. These core criteria, however, are often accompanied by numerous comorbidities, many of which result in severe negative impacts on quality of life, including seizures, epilepsy, sleep disturbance, hypotonia, and GI distress. While ASD is a clinically heterogeneous disorder, gastrointestinal (GI) distress is among the most prevalent co-occurring symptom complex, manifesting in upward of 70% of all individuals with ASD. Read More

View Article and Full-Text PDF

Prognostic Significance of Autophagy-Relevant Gene Markers in Colorectal Cancer.

Front Oncol 2021 15;11:566539. Epub 2021 Apr 15.

Department of Pathology, Guangdong Medical University, Dongguan, China.

Background: Colorectal cancer (CRC) is a common malignant solid tumor with an extremely low survival rate after relapse. Previous investigations have shown that autophagy possesses a crucial function in tumors. However, there is no consensus on the value of autophagy-associated genes in predicting the prognosis of CRC patients. Read More

View Article and Full-Text PDF

Generation and Application of a Reporter Cell Line for the Quantitative Screen of Extracellular Vesicle Release.

Front Pharmacol 2021 16;12:668609. Epub 2021 Apr 16.

Moores Cancer Center, University of California, San Diego, La Jolla, CA, United States.

Extracellular vesicles (EVs) are identified as mediators of intercellular communication and cellular regulation. In the immune system, EVs play a role in antigen presentation as a part of cellular communication. To enable drug discovery and characterization of compounds that affect EV biogenesis, function, and release in immune cells, we developed and characterized a reporter cell line that allows the quantitation of EVs shed into culture media in phenotypic high-throughput screen (HTS) format. Read More

View Article and Full-Text PDF

Infectious disease screening in a dedicated primary care clinic for children in foster care.

Child Abuse Negl 2021 Apr 28;117:105074. Epub 2021 Apr 28.

Children's Health System, 1935 Medical District Drive, Dallas, TX 75219, United States.

Background: Children in foster care are considered at high risk for infectious diseases, and guidelines recommend screening for tuberculosis, hepatitis B and C, syphilis, gonorrhea and chlamydia. Little is known about the prevalence of infectious disease in children in foster care.

Objectives: Describe infectious disease screening practices in a primary care clinic dedicated to caring for children in foster care. Read More

View Article and Full-Text PDF

Insecticidal and Attractant Activities of Leaf Essential Oil against Two Major Pests from Diptera: (Culicidae) and (Tephritidae).

Molecules 2021 Apr 16;26(8). Epub 2021 Apr 16.

United States Department of Agriculture-Agricultural Research Service (USDA-ARS), Subtropical Horticulture Research Station (SHRS), 13601 Old Cutler Rd., Miami, FL 33158, USA.

In this study, Noot and Chalermglin (Magnoliaceae) essential oil (MCEO) was evaluated for insecticidal activity against the yellow fever mosquito and attractant activity for the Mediterranean fruit fly . The leaves of (Giổi chanh) were collected from northwestern Vietnam, and the water-distilled MCEO was analyzed by gas-chromatography and mass spectrometry (GC-MS). The major constituents of MCEO were identified as linalool 19%, geranial 16%, citronellal 14%, neral 14%, and sabinene 12%. Read More

View Article and Full-Text PDF

Genome-wide CRISPR screens reveal synthetic lethal interaction between CREBBP and EP300 in diffuse large B-cell lymphoma.

Cell Death Dis 2021 Apr 28;12(5):419. Epub 2021 Apr 28.

Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoid malignancy and a highly heterogeneous disease. In this study, we performed whole-genome and transcriptome sequencing, and a genome-wide CRISPR-Cas9-knockout screen to study an activated B-cell-like DLBCL cell line (RC-K8). We identified a distinct pattern of genetic essentialities in RC-K8, including a dependency on CREBBP and MDM2. Read More

View Article and Full-Text PDF

Vibrio cholerae Sialidase-Specific Immune Responses Are Associated with Protection against Cholera.

mSphere 2021 Apr 28;6(2). Epub 2021 Apr 28.

Infectious Diseases Division, icddr,b (International Centre for Diarrhoeal Disease Research, Bangladesh), Dhaka, Bangladesh

Cholera remains a major public health problem in resource-limited countries. Vaccination is an important strategy to prevent cholera, but currently available vaccines provide only 3 to 5 years of protection. Understanding immune responses to cholera antigens in naturally infected individuals may elucidate which of these are key to longer-term protection seen following infection. Read More

View Article and Full-Text PDF

How Zebrafish Can Drive the Future of Genetic-based Hearing and Balance Research.

J Assoc Res Otolaryngol 2021 Jun 28;22(3):215-235. Epub 2021 Apr 28.

Section On Sensory Cell Development and Function, National Institutes On Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, USA.

Over the last several decades, studies in humans and animal models have successfully identified numerous molecules required for hearing and balance. Many of these studies relied on unbiased forward genetic screens based on behavior or morphology to identify these molecules. Alongside forward genetic screens, reverse genetics has further driven the exploration of candidate molecules. Read More

View Article and Full-Text PDF

Structure-guided Design of G Protein-coupled Receptor Polypharmacology.

Angew Chem Int Ed Engl 2021 Apr 27. Epub 2021 Apr 27.

Uppsala University, Dept. of Cell and Molecular Biology, Husargatan 3 Box 596, 751 24, Uppsala, SWEDEN.

Many diseases are polygenic and can only be treated efficiently with drugs that modulate multiple targets. However, rational design of compounds with multi-target profiles is rarely pursued because it is considered too difficult, in particular if the drug must enter the CNS. Here, a structure-based strategy to identify dual-target ligands of G protein-coupled receptors is presented. Read More

View Article and Full-Text PDF

Improved Maternal and Infant Outcomes with Serial, Self-Reported Early Prenatal Substance Use Screening.

Matern Child Health J 2021 Apr 27. Epub 2021 Apr 27.

Division of Neonatology, Department of Pediatrics, Froedtert Health & the Medical College of Wisconsin, 8701 W Watertown Plank Rd, Wauwatosa, WI, 53226, USA.

Introduction: Most screening tools identifying women with substance use are not validated, used once in pregnancy, and are not reflective of continued substance use. We hypothesized that serial early prenatal substance screening leads to decreased substance use by the end of pregnancy and improved outcomes.

Methods: This is a retrospective cohort study of mothers and their infants between 1/2015 and 12/2017. Read More

View Article and Full-Text PDF

PAX8 and MECOM are interaction partners driving ovarian cancer.

Nat Commun 2021 04 26;12(1):2442. Epub 2021 Apr 26.

Chemical Biology and Therapeutics, Novartis Institutes for Biomedical Research, Basel, Switzerland.

The transcription factor PAX8 is critical for the development of the thyroid and urogenital system. Comprehensive genomic screens furthermore indicate an additional oncogenic role for PAX8 in renal and ovarian cancers. While a plethora of PAX8-regulated genes in different contexts have been proposed, we still lack a mechanistic understanding of how PAX8 engages molecular complexes to drive disease-relevant oncogenic transcriptional programs. Read More

View Article and Full-Text PDF

A Small-Scale shRNA Screen in Primary Mouse Macrophages Identifies a Role for the Rab GTPase Rab1b in Controlling Typhi Growth.

Front Cell Infect Microbiol 2021 7;11:660689. Epub 2021 Apr 7.

Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.

Typhi is a human-restricted bacterial pathogen that causes typhoid fever, a life-threatening systemic infection. A fundamental aspect of . Typhi pathogenesis is its ability to survive in human macrophages but not in macrophages from other animals (i. Read More

View Article and Full-Text PDF

RNF217 regulates iron homeostasis through its E3 ubiquitin ligase activity by modulating ferroportin degradation.

Blood 2021 Apr 25. Epub 2021 Apr 25.

Zhejiang University School of Medicine, Hangzhou, China.

Ferroportin (FPN), the body's sole iron exporter, is essential for maintaining systemic iron homeostasis. In response to either increased iron or inflammation, hepatocyte-secreted hepcidin binds to FPN, inducing its internalization and subsequent degradation. However, the E3 ubiquitin ligase that underlies FPN degradation has not been identified. Read More

View Article and Full-Text PDF

PBRM1 Deficiency Confers Synthetic Lethality to DNA Repair Inhibitors in Cancer.

Cancer Res 2021 Apr 22. Epub 2021 Apr 22.

ATIP-Avenir group, Inserm Unit U981, Gustave Roussy, Villejuif, France.

Inactivation of (), a specific subunit of the PBAF chromatin remodeling complex, occurs frequently in cancer, including 40% of clear cell renal cell carcinomas (ccRCC). To identify novel therapeutic approaches to targeting PBRM1-defective cancers, we used a series of orthogonal functional genomic screens that identified PARP and ATR inhibitors as being synthetic lethal with deficiency. The PBRM1/PARP inhibitor synthetic lethality was recapitulated using several clinical PARP inhibitors in a series of model systems and in a xenograft model of ccRCC. Read More

View Article and Full-Text PDF

Selective modulation of a pan-essential protein as a therapeutic strategy in cancer.

Cancer Discov 2021 Apr 21. Epub 2021 Apr 21.

Department of Pediatric Oncology, Dana-Farber Cancer Institute

Cancer dependency maps, which use CRISPR/Cas9 depletion screens to profile the landscape of genetic dependencies in hundreds of cancer cell lines, have identified context-specific dependencies that could be therapeutically exploited. An ideal therapy is both lethal and precise, but these depletion screens cannot readily distinguish between gene effects that are cytostatic or cytotoxic. Here, we employ a diverse panel of functional genomic screening assays to identify NXT1 as a selective and rapidly lethal in vivo-relevant genetic dependency in MYCN-amplified neuroblastoma. Read More

View Article and Full-Text PDF

Why does SARS-CoV-2 hit in different ways? Host genetic factors can influence the acquisition or the course of COVID-19.

Eur J Med Genet 2021 Apr 16;64(6):104227. Epub 2021 Apr 16.

Scuola di Specializzazione in Pediatria, Università degli Studi di Trieste, 34127, Trieste, Italy. Electronic address:

The identification of high-risk factors for the infection by SARS-CoV-2 and the negative outcome of COVID-19 is crucial. The genetic background of the host might account for individual responses to SARS-CoV-2 infection besides age and comorbidities. A list of candidate polymorphisms is needed to drive targeted screens, given the existence of frequent polymorphisms in the general population. Read More

View Article and Full-Text PDF

Tobacco transcription factor bHLH123 improves salt tolerance by activating NADPH oxidase NtRbohE expression.

Plant Physiol 2021 Apr 19. Epub 2021 Apr 19.

College of Horticulture, Qingdao Agricultural University, Qingdao 266101, Shandong Province, China.

In plants, reactive oxygen species (ROS) produced following the expression of the respiratory burst oxidase homolog (Rboh) gene are important regulators of stress responses. However, little is known about how plants acclimate to salt stress through the Rboh-derived ROS signaling pathway. Here, we showed that a 400-bp fragment of the tobacco (Nicotiana tabacum) NtRbohE promoter played a critical role in the salt response. Read More

View Article and Full-Text PDF

Development of a patient-reported outcome measure for patients who have recovered from a subarachnoid hemorrhage: the "questionnaire for the screening of symptoms in aneurysmal subarachnoid hemorrhage" (SOS-SAH).

BMC Neurol 2021 Apr 16;21(1):162. Epub 2021 Apr 16.

Department of Neurosurgery, Radboud University Medical Center, HB, 6500, Nijmegen, the Netherlands.

Background: Patients who have been successfully treated for an aneurysmal subarachnoid hemorrhage (aSAH) often retain multiple health complaints, including mood disorders, cognitive complaints, fatigue, and problems with social participation. These problems are not always fully addressed during hospital visits or in current outcome measures, such as the modified Rankin score and the Glasgow Outcome Scale. Here, we present the development of the "Questionnaire for the Screening of Symptoms in aneurysmal Subarachnoid Hemorrhage" (SOS-SAH), which screens for the self-reported symptoms of patients with mild disabilities. Read More

View Article and Full-Text PDF

The impact of removing former drinkers from genome-wide association studies of AUDIT-C.

Addiction 2021 Apr 16. Epub 2021 Apr 16.

Yale University School of Public Health, New Haven, CT, USA.

Background And Aims: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire screens for harmful drinking using a 12-month timeframe. A score of 0 is assigned to individuals who report abstaining from alcohol in the past year. However, many middle-age individuals reporting current abstinence are former drinkers (FDs). Read More

View Article and Full-Text PDF

Genetic Mapping of a new allele, in .

MicroPubl Biol 2021 Apr 8;2021. Epub 2021 Apr 8.

School of Science, Technology, and Mathematics, Ohio Northern University, Ada, OH USA.

Genetic screens provide a mechanism to identify genes involved with different cellular and organismal processes. Using a Flp/FRT screen in the eye we identified mutations that result in alterations and de-regulation of cell growth and division. From this screen a group of undergraduate researchers part of the Fly-CURE consortium mapped and characterized a new allele of the gene , Read More

View Article and Full-Text PDF