Tag: IC50

Invivyd, Inc. Announces Positive Initial Results from Ongoing CANOPY Phase 3 Pivotal Clinical Trial Investigating VYD222 for the Prevention of COVID-19 -December 18, 2023 at 07:00 am EST

Invivyd, Inc. announced positive initial results from the ongoing CANOPY Phase 3 pivotal clinical trial of VYD222, a broadly neutralizing, half-life extended monoclonal antibody candidate, for the prevention of symptomatic COVID-19. “VYD222 produced high serum virus neutralizing antibody (sVNA) titer levels against XBB.1.5 in the IC cohort, essentially replicating the…

Continue Reading Invivyd, Inc. Announces Positive Initial Results from Ongoing CANOPY Phase 3 Pivotal Clinical Trial Investigating VYD222 for the Prevention of COVID-19 -December 18, 2023 at 07:00 am EST

Invivyd Announces Positive Initial Results from Ongoing

VYD222 produced high serum virus neutralizing antibody titer levels in immunocompromised participants Data supportive of an immunobridging approach to the EVADE study of adintrevimab Overall favorable safety and tolerability profile of VYD222 including no study drug-related serious adverse events (SAEs) to date VYD222 demonstrates continued in-vitro neutralization activity against major…

Continue Reading Invivyd Announces Positive Initial Results from Ongoing

Evidence of an intracellular creatine-sensing mechanism that modulates creatine biosynthesis via AGAT expression in human HAP1 cells

Cell lines and reagents HAP1 cells used to generate the reporter cells were grown from a frozen stock of HAP1 (C859) passage 6 purchased from Horizon Discovery LTD (Cambridge, UK). Iscove’s media (Ref: 098–150, Wisent) supplemented with 10% Fetal Bovine serum (Multicell) was used to grow HAP1 cells. All cells…

Continue Reading Evidence of an intracellular creatine-sensing mechanism that modulates creatine biosynthesis via AGAT expression in human HAP1 cells

Fatty Acid Metabolism-Related lncRNAs as Biomarkers for SKCM

Introduction Skin cutaneous melanoma (SKCM), as one of the most aggressive types of cancer due to its elevated degree of heterogeneity, has gained increasing attention during the past few decades.1 Also known as “the cancer that rises with the sun”,2 melanoma originates from cancerous melanocytes due to molecular or genetic…

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Investigating the prognostic value of mTORC1 signaling in bladder cancer via bioinformatics evaluation

mTORC1 signaling in bladder cancer Initially, we assessed the mTORC1 signaling scores of both normal and bladder cancer samples. We analyzed the TCGA dataset and observed that the mTORC1 signaling score in normal tissues was considerably lower than that in breast cancer tissue samples (Fig. 2A). We analyzed the expression of…

Continue Reading Investigating the prognostic value of mTORC1 signaling in bladder cancer via bioinformatics evaluation

Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2

Study design, ethical statement, and sample collection The vaccinated participants were recruited under the COVID-19 PROTECT study (2012/00917). The convalescent plasma samples were collected from subjects who were diagnosed with COVID-19 by positive polymerase chain reaction (PCR) results (study 2020/00120). All participants provided written informed consent in accordance with the…

Continue Reading Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2

Comparative Structure Based Virtual Screening Utilizing Optimized AlphaFold Model Identifies Selective HDAC11 Inhibitor | Biological and Medicinal Chemistry | ChemRxiv

Abstract HDAC11 is a class IV histone deacylase with no crystal structure reported so far. The catalytic domain of HDAC11 shares low sequence identity with other HDAC isoforms which makes the conventional homology modeling less reliable. AlphaFold is a neural network machine learning approach that can predict the 3D structure…

Continue Reading Comparative Structure Based Virtual Screening Utilizing Optimized AlphaFold Model Identifies Selective HDAC11 Inhibitor | Biological and Medicinal Chemistry | ChemRxiv

A dual-targeted drug inhibits cardiac ryanodine receptor Ca2+ leak but activates SERCA2a Ca2+ uptake

Introduction During each heartbeat, the intracellular calcium concentration ([Ca2+]i) cycles dynamically between low resting diastolic and high active systolic levels within cardiomyocytes (Bers, 2002; Eisner et al, 2017; Sankaranarayanan et al, 2017): upon electrical excitation, Ca2+ influx via voltage-gated CaV1.2 channels activates Ca2+-induced Ca2+ release via SR ryanodine receptor type…

Continue Reading A dual-targeted drug inhibits cardiac ryanodine receptor Ca2+ leak but activates SERCA2a Ca2+ uptake

What is CYP2D6 responsible for?

The CYP2D6 enzyme catalyses the metabolism of a large number of clinically important drugs including antidepressants, neuroleptics, some antiarrhythmics, lipophilic β-adrenoceptor blockers and opioids. Takedown request View complete answer on ncbi.nlm.nih.gov What is the role of the CYP2D6 enzyme? One such member, CYP2D6 is involved in the metabolism of a…

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Relay: Market Underestimating Lirafugratinib’s Potential (Upgrade) (RLAY)

Anchiy At a Glance Relay Therapeutics (NASDAQ:RLAY) has reached a critical phase, juxtaposing strong financial foundations against increasing operational costs, which I have previously analyzed in depth. Since my last evaluation, lirafugratinib’s clinical momentum has been maintained in the Phase 1/2 ReFocus trial, showing significant promise for FGFR2-altered cholangiocarcinoma, although…

Continue Reading Relay: Market Underestimating Lirafugratinib’s Potential (Upgrade) (RLAY)

Preparation and in vitro Activity of Anti-EpCAM Immunotoxin

     Preparation and in vitro Activity of Anti-EpCAM Immunotoxin LIU Yu-ping1,DENG Chang-ping2,MA Xing-yuan2,LIU Qiu-li1,BAO Wen1,ZHENG Wen-yun1,**() 1 Shanghai Key Laboratory…

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Design, optimization, production and activity testing of recombinant immunotoxins expressed in plants and plant cells for the treatment of monocytic leukemia

. 2023 Dec;14(1):2244235. doi: 10.1080/21655979.2023.2244235. Affiliations Expand Affiliations 1 Bioprocess Engineering, Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Aachen, Germany. 2 Institute for Molecular Biotechnology, RWTH Aachen University, Aachen, Germany. 3 University of Natural Resources and Life Sciences, Vienna (BOKU), Department of Biotechnology (DBT), Institute of Bioprocess Science…

Continue Reading Design, optimization, production and activity testing of recombinant immunotoxins expressed in plants and plant cells for the treatment of monocytic leukemia

Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer

Mice strains Six- to eight-week-old (age), 20–25-g (weight), both male and female (sex) mice were used for tumor xenografts generation and in vivo efficacy studies as described in the text (see Table 3). Athymic Nude (Envigo) Foxn1nu/Foxn1+ or NOD.Cg Prkdcscid Il2rgtm1Wjl/SzJ also called NSG mice were used. All animal procedures were…

Continue Reading Characterizing the regulatory Fas (CD95) epitope critical for agonist antibody targeting and CAR-T bystander function in ovarian cancer

Rapid discovery of high-affinity antibodies via massively parallel sequencing, ribosome display and affinity screening

Construct design To transcribe and translate sequenced DNA clusters on an Illumina flow cell, our DNA constructs contained the following elements: a P5 adaptor, followed by a 28 nt unique barcode, a 27 nt unstructured spacer (5p UNS v2), a ribosome binding site, start codon, protein coding region, TolAk short linker, 2×…

Continue Reading Rapid discovery of high-affinity antibodies via massively parallel sequencing, ribosome display and affinity screening

In Vitro and In Vivo Evaluation of Photocontrolled Biologically Active Compounds – Potential Drug Candidates for Cancer Photopharmacology

Photocontrolled, biologically active compounds contain reversibly photoisomerizable fragments, photoswitches in their molecules. Compounds are cyclic peptides modified by a diarylethene fragment that undergoes reversible light-induced electrocyclic transformations. They can photoswitch, that is, toggle between a UV-generated, biologically inactive form and a red light-generated, biologically active form. It is believed that…

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Broad sialic acid usage amongst species D human adenovirus

Generation and purification of recombinant fiber knob proteins pQE expression plasmids (Qiagen, Manchester, UK) containing DNA encoding species D fiber knob proteins were produced by TWIST Biosciences (San Francisco, USA). The vectors were transformed by heat shock into competent SG13009 Escherichia coli (E.coli) bacteria containing a pREP4–4 plasmid. Heat shock…

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Acquisition of fluoroquinolone resistance in E. coli

1Division of Clinical Infectious Diseases & Chemotherapy, Tohoku Medical and Pharmaceutical University, Sendai, Japan; 2Department of Pharmacy, Japan Labor Health and Welfare Organization Tohoku Rosai Hospital, Sendai, Japan Correspondence: Takumi Sato, Division of Clinical Infectious Diseases & Chemotherapy, Tohoku Medical and Pharmaceutical University, 4-4-1, Komatsushima, Aoba-ku, Sendai, 981-8558, Japan, Tel…

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A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses

Phylogenetic analysis Protein sequences of spike proteins were downloaded from the NCBI virus database for all the known sarbecoviruses (June 2020). A multiple sequence alignment was generated using MUSCLE36. The resulting multiple sequence alignment was pruned to the RBD region, filtered at 95% sequence identity and used as input for…

Continue Reading A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses

Upregulation of WDR6 drives hepatic de novo lipogenesis in insulin resistance in mice

WDR6 is upregulated in response to insulin during insulin resistance We created an IR mouse model by feeding animals a HFD for 6 weeks20. Insulin injection was then performed (Fig. 1a). The phosphorylation of AKT, a key readout of the insulin signalling pathway21, showed decreased response to insulin, indicating resistance…

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The impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer

Genomic analysis and cohort description We generated whole-exome sequencing (WES) and RNA sequencing (RNA-Seq) data from tumors and blood samples from 27 advanced urothelial cancer patients treated with anti-PD-1/PD-L1 ICIs at Hospital del Mar (Fig. 1a). WES data was obtained from the tumors before treatment as well as from blood samples,…

Continue Reading The impact of mutational clonality in predicting the response to immune checkpoint inhibitors in advanced urothelial cancer

Conjugation of microbial-derived gold nanoparticles to different types of nucleic acids: evaluation of transfection efficiency

AuNP production Fusarium oxysporum was used for the extracellular production of AuNP. The fungus was acquired from the Culture Collection of Fungi of the Charles University (CCF 3732, Czech Republic). After cultivation in Sabouraud Dextrose Broth (SDB, Sigma Aldrich, Prague, Czech Republic) at 30 °C and 150 rpm for 4 days, the supernatant…

Continue Reading Conjugation of microbial-derived gold nanoparticles to different types of nucleic acids: evaluation of transfection efficiency

Accelerated evolution of SARS-CoV-2 in free-ranging white-tailed deer

Sample collection Previously, we collected nasal samples from WTD in northeastern Ohio focusing on metropolitan area parks11. In the present study, we expanded geographical study area by approximately 1000-fold to target the entire state of Ohio. We collected 1522 nasal swabs from WTD across 83 of Ohio’s 88 counties from…

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An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants

Protein expression hACE2-hIgG1 was constructed by fusing the extracellular domain of human ACE2 (amino acid 19–615) (UniProt Q9BYF1) to the human IgG1 hinge and Fc (UniProt P01857). H374N and H378N mutations were introduced to inactivate the Zinc metallo-enzyme activity17. HH-120 was constructed by fusing hACE2-hIgG1 with an IgM tailpiece (PTLYNVSLVMSDTAGTCY)33….

Continue Reading An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants

Plant-derived nanovesicles facilitate tumor therapy

Introduction Tumors are the second leading cause of death worldwide, with approximately 1670 deaths per day in the United States and 7700 deaths per day in China.1,2 The fundamental reason why cancers are still considered “frightening” is the difficulty of early tumor detection and the variety of issues present in…

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Ulcerative Colitis Treatment by CLP loaded with NLRP3 siRNA

Introduction Since the 20th century, tThe incidence of ulcerative colitis (UC) has been increasing over time, negatively affecting peoples’ health.1,2 UC is a multifactorial induced inflammatory bowel disease (IBD) characterized by chronic recurrent and remitting mucosal inflammation.3,4 It originates in the rectum and then extends to the proximal segments of…

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Profile of relugolix | DDDT

Introduction Prostate cancer remains one of the most commonly diagnosed malignancies among men.1,2 Moreover, the number of cancer-related deaths throughout the world has increased from 307,500 in 20121 to 375,304 in 2020.2 Although definitive therapy, such as radical prostatectomy and irradiation, offers excellent oncologic outcomes in most men with localized…

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Comprehensive analysis of m6A regulators associated with immune infiltration in Hepatitis B virus-related hepatocellular carcinoma | BMC Gastroenterology

M6A regulators are likely to have a significant effect on HBV-related HCC Twenty m6A regulators, including 12 readers, 7 writers, and 1 eraser, were identified in the TCGA and GEO cohorts. The correlation network provided interactive information among the m6A regulators. The ratio of somatic mutations and CNV for the…

Continue Reading Comprehensive analysis of m6A regulators associated with immune infiltration in Hepatitis B virus-related hepatocellular carcinoma | BMC Gastroenterology

FDA Drug Approvals April-June 2023

Oncology Columvi (glofitamab) Glofitamab is a bispecific CD3-directed and CD20-directed antibody that binds to CD20 expressed on the surface of B cells and to CD3 receptor expressed on the surface of T cells. It causes T-cell activation and proliferation, secretion of cytokines, and lysis of CD20-expressing B cells. Glofitamab is…

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The effective treatment of malignant melanoma.

Plain-Language Summary Malignant melanoma (MM) is the most lethal skin cancer. Recent studies have found that the invasion and metastasis of MM are related not only to MM gene mutation but also to the interaction between MM cells and the immune system and microenvironment. The application of RNAi-based therapeutics to…

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Cancers | Free Full-Text | A Novel Bispecific Antibody for EpCAM-Directed Inhibition of the CD73/Adenosine Immune Checkpoint in Ovarian Cancer

1. Introduction Typically, tumors in patients with ovarian cancer (OC) are often diagnosed at an advanced stage [1]. Currently, cytoreductive therapy with platinum-based chemotherapy is the mainstay of disease management, to which the majority of patients with OC initially respond. Unfortunately, 70% of these patients eventually develop refractory recurrences [2]….

Continue Reading Cancers | Free Full-Text | A Novel Bispecific Antibody for EpCAM-Directed Inhibition of the CD73/Adenosine Immune Checkpoint in Ovarian Cancer

In vitro and in vivo characterization of SARS-CoV-2 resistance to ensitrelvir

Ethics All animal experiments were conducted in accordance with the University of Tokyo’s Regulations for Animal Care and Use, which were approved by the Animal Experiment Committee of the Institute of Medical Science, the University of Tokyo. The committee acknowledged and accepted both the legal and ethical responsibility for the…

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The opioid tramadol blocks the cardiac sodium channel Nav1.5 in HEK293 cells

Background and aims: Opioids are associated with increased risk of sudden cardiac death. This may be due to their effects on the cardiac sodium channel (Nav1.5) current. In the present study, we establish whether tramadol, fentanyl, or codeine affect Nav1.5 current. Methods: Using whole-cell patch-clamp methodology, we studied the effects…

Continue Reading The opioid tramadol blocks the cardiac sodium channel Nav1.5 in HEK293 cells

An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma | BMC Cancer

The mRNA expression levels of CBX family in DLBCL patients To explore the expression differences of the CBX family in DLBCL patients, the GEPIA database was used (Fig. 2). Based on the data obtained from GEPIA, the expression levels of CBX1, CBX2, CBX3, CBX5, CBX6, and CBX8 in DLBCL were higher…

Continue Reading An integrative bioinformatics investigation and experimental validation of chromobox family in diffuse large B-cell lymphoma | BMC Cancer

The effect of inhibition of receptor tyrosine kinase AXL on DNA damage response in ovarian cancer

Cell lines and culture conditions All media and supplements were purchased from Gibco unless otherwise stated. OC cell line SKOV3, OVCA429, CH1 and NSCLC cell line H1299 and A549 were maintained using Dulbecco’s Modified Eagle Medium (DMEM) media supplemented with 10% (v/v) foetal bovine serum (FBS). OC cell lines HeyA8,…

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ICML 2023 Meeting: CFT7455 in NHL Preclinical Presentation

CFT7455: A novel IKZF1/3 degrader, demonstrates potent anti-tumor activity in peripheral and CNS models of non-Hodgkin’s lymphoma as a single agent or in combination with clinically approved agents Samantha Perino, R. Jason Kirby, Roman V. Agafonov, Prasoon Chaturvedi, Scott J. Eron, Andrew Good, June A. Hart, Minsheng…

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Scientists unlock virus-fighting power with synthetic nanobody platform

In a recent study published in the Proceedings of the National Academy of Sciences, researchers developed a fully synthetic platform for nanobody generation. Study: Fully synthetic platform to rapidly generate tetravalent bispecific nanobody–based immunoglobulins. Image Credit: Adao / Shutterstock.com What are nanobodies? Biologics have been increasingly used for the treatment or prevention…

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Exploring the potential role of defensins in differential vector competence of body and head lice for Bartonella quintana | Parasites & Vectors

Amino acid alignments and phylogenetic analysis of defensins 1 and 2 of body and head lice Defensins 1 and 2 of the body and head lice were aligned using the CLC Main Workbench 8 (Qiagen, Hilden, Germany) (Fig. 1). The open reading frame (ORF) sequences of body louse defensin 1 (BLDef1)…

Continue Reading Exploring the potential role of defensins in differential vector competence of body and head lice for Bartonella quintana | Parasites & Vectors

Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants

Emergence of a novel BA.1 sublineage through intrahost evolution We performed genomic analysis of serially collected nasopharyngeal (NP) and anterior nares (AN) samples from an immunocompromised patient (P1) with diffuse B-cell lymphoma and persistent SARS-CoV-2 Omicron BA.1 replication between December 2021 and March 2022. Over a 12-week period, we documented…

Continue Reading Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants

Positive beta-scores of essential genes in drug-treated cells

Positive beta-scores of essential genes in drug-treated cells 0 @ea5b2e2a Last seen 14 hours ago Finland Hi, I ran both MAGECK RRA and MAGECK MLE on my CRISPRi screen data set where I have samples: DMSO control day 0 DMSO control day 18 (end of experiment) drug 1 day 18…

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Pan-KRAS inhibitor disables oncogenic signalling and tumour growth

KRAS mutations are among the most frequent gain-of-function alterations found in patients with cancer and their therapeutic targeting has long been a key objective in precision oncology8,9,10,11,12. The KRAS GTPase cycles between an active (GTP-bound) and an inactive (GDP-bound) state. GTP hydrolysis is enhanced by GTPase-activating proteins13, whereas GDP to…

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Generation of a mutator parasite to drive resistome discovery in Plasmodium falciparum

CRISPR editing of DNA polymerase δ To increase the genetic repertoire of P. falciparum parasites in culture, we aimed to generate parasites with impaired 3ʹ−5ʹ proof-reading activity from the catalytic subunit of DNA polymerase δ (PF3D7_1017000) in order to increase the level of basal spontaneous mutations, based on prior work…

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ncRNA | Free Full-Text | Inverse Impact of Cancer Drugs on Circular and Linear RNAs in Breast Cancer Cell Lines

Received: 19 January 2023 / Revised: 2 May 2023 / Accepted: 16 May 2023 / Published: 19 May 2023 Round 1 Reviewer 1 Report Terrazan and coworkers presented the manuscript entitled “ Inverse impact of cancer drugs on circular and linear RNAs in 2 breast cancer cell lines ”. The…

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Pinostrobin, a fingerroot compound, regulates miR-181b-5p and induces acute leukemic cell apoptosis

Leukemia cell culture The human acute promyelocytic leukemia cell line (NB4) and the human acute lymphocytic leukemia cell line (MOLT-4) were purchased from Cell Lines Service (Eppelheim, Germany). Leukemia cells were cultured in RPMI-1640 medium supplemented with 10% (v/v) FBS and 1% (v/v) penicillin–streptomycin (Gibco Life Technologies, Waltham, MA, USA)….

Continue Reading Pinostrobin, a fingerroot compound, regulates miR-181b-5p and induces acute leukemic cell apoptosis

Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1

Ethics approval and consent to participate The study was performed in accordance with the Guide for the Care and Use of Laboratory Animals of the US National Institutes of Health (NIH). The Seattle Children’s Research Institute (SCRI) has an Assurance from the Public Health Service through the Office of Laboratory…

Continue Reading Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1

Toxic mechanisms of MWCNTs for ocular cells.

Introduction Carbon nanotubes (CNTs) are nano-sized one-dimensional tubular structures rolled by single (single-walled CNTs, SWCNTs) or multiple layers (multi-walled CNTs, MWCNTs) of graphene with unique electrochemical, mechanical and thermal properties, which render them as attracted engineered nanomaterials for various commercial applications.1–4 An increase in the production and utilization of CNTs…

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Comprehensive prediction of immune microenvironment and hot and cold tumor differentiation in cutaneous melanoma based on necroptosis-related lncRNA

Identify necroptosis-related lncRNAs in SKCM There are 386 necroptosis-related lncRNAs identified from the data of TCGA and GTEx, as the standard is the coefficients > 0.4 and P < 0.001. After that, flowing the differential expression analysis, 87 necroptosis-related lncRNAs were found to display significantly differential expression with the screen value as |logFC…

Continue Reading Comprehensive prediction of immune microenvironment and hot and cold tumor differentiation in cutaneous melanoma based on necroptosis-related lncRNA

Metagenomics-enabled reverse-genetics assembly and characterization of myotis bat morbillivirus

Ethics declaration Animal study was performed following the Guide for the Care and Use of Laboratory Animals. Animal experiment was approved by the Institutional Animal Care and Use Committee of Colorado State University (protocol number 1090) in advance and conducted in compliance with the Association for the Assessment and Accreditation…

Continue Reading Metagenomics-enabled reverse-genetics assembly and characterization of myotis bat morbillivirus

Epigenetic priming improves salvage chemotherapy in diffuse large B-cell lymphoma via endogenous retrovirus-induced cGAS-STING activation | Clinical Epigenetics

5-Azacytidine pretreatment resensitizes cisplatin-resistant DLBCL cell lines to cisplatin to varying degrees A platinum-based anti-neoplastic agent is an essential component of salvage regimens for aggressive lymphomas, for example, rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDP) for relapsed/refractory DLBCL and Hodgkin lymphoma [21]. As a single agent in humans, cisplatin is administered…

Continue Reading Epigenetic priming improves salvage chemotherapy in diffuse large B-cell lymphoma via endogenous retrovirus-induced cGAS-STING activation | Clinical Epigenetics

Efficient evolution of human antibodies from general protein language models

Acquiring amino acid substitutions via language model consensus We select amino acid substitutions recommended by a consensus of language models. We take as input a single wild-type sequence x = (x1,…,xN)∈ \(\mathcal{X}\)N, where \(\mathcal{X}\) is the set of amino acids, and N is the sequence length. We also require a set of…

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“Feature Selection MRMR

hi everyone , I have question about this code: data <- mRMR.data(data = data.frame(target=cgps.ic50, cgps.ge)) a<-mRMR.ensemble(data = data, target_indices = 1, feature_count = 30, solution_count = 1). is the a@scores[[“1”]] are the 30 top features?? and the second question is how can i get it with the names of features??…

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Structure of anhydrotetracycline-bound Tet(X6) reveals the mechanism for inhibition of type 1 tetracycline destructases

Tet(X6) contains a conserved architecture of type 1 tetracycline destructases We determined the X-ray structure of Tet(X6) at 2.2 Å resolution with Rfree/Rwork of 0.22/0.19 (Table 1). This FAD complexed, anhydrotetracycline-free enzyme structure consists of a conserved architecture for type 1 TDases: a characteristic Rossman fold containing an FAD-binding domain, a…

Continue Reading Structure of anhydrotetracycline-bound Tet(X6) reveals the mechanism for inhibition of type 1 tetracycline destructases

Data of InnoCare’s Robust Oncology Pipelines Presented at the 2023 AACR Annual Meeting

News and research before you hear about it on CNBC and others. Claim your 1-week free trial to StreetInsider Premium here. BEIJING–(BUSINESS WIRE)– Data of InnoCare’s (HKEX: 09969; SSE: 688428) robust oncology pipelines were presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting. Oral Presentation: ICP-490 is…

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The prognostic value of hedgehog signaling in bladder cancer by integrated bioinformatics

HhS activation is a marker of poor prognosis in BLCA patients First, HhS scores were calculated and its expression characteristics were analyzed for patients in the TGCA-BLCA cohort. The results showed that HhS was overactivated in patients with higher stage and older age (Fig. 2A, B). And there is no significant…

Continue Reading The prognostic value of hedgehog signaling in bladder cancer by integrated bioinformatics

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

IgG plasmids Antibody sequences and Fc-tagged ACE2 were cloned into the CMV/R plasmid backbone for expression under a CMV promoter. The antibodies with variable HC/LC were cloned between the CMV promoter and the bGH poly(A) signal sequence of the CMV/R plasmid to facilitate improved protein expression. The variable region was…

Continue Reading A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates

Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis

Design and synthesis of indolyl pyrimidinamine inhibitors of TTBK1/2 Our lead (AMG28, Fig. 1A) emerged from examination of the off-target activity of a published Amgen NF-κB inducing kinase (NIK) inhibitor27. The potency of AMG28 was reported in the MRC Kinase Profiling Inhibitor Database as 8% activity remaining for TTBK1 and 12%…

Continue Reading Modulation of tau tubulin kinases (TTBK1 and TTBK2) impacts ciliogenesis

Nanoparticle-based combination therapy for ovarian cancer

Introduction Ovarian cancer is one of the most common gynecologic malignancies with high morbidity.1 Due to its relatively asymptomatic nature, about 70% of patients are diagnosed at an advanced stage and have poor prognosis, leading to high mortality rates.2,3 The clinical treatment of ovarian cancer mainly relies on chemotherapy after…

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A Vaccinia-based system for directed evolution of GPCRs in mammalian cells

Poxvirus vectors for directed evolution of GPCRs in mammalian cells Monoclonal and homogenous expression of the gene of interest are critical prerequisites for selections in directed evolution that are difficult to achieve in mammalian cells with common expression strategies such as transient transfection. To reach both equal gene dosage and…

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Isoform-specific knockdown of long and intermediate prolactin receptors interferes with evolution of B-cell neoplasms

Knockdown of LFPRLR reduces splenic B-cell subsets in SLE-prone mice To investigate whether the PRL-LFPRLR axis raises the risk of initiation of B-cell malignancies, we compared SLE-prone MRL-lpr mice treated with either control SMO or LFPRLR SMO. Among SLE-prone models, we chose MRL-lpr mice because they accumulate genetic lesions indicative…

Continue Reading Isoform-specific knockdown of long and intermediate prolactin receptors interferes with evolution of B-cell neoplasms

From a genome-wide screen of RNAi molecules against SARS-CoV-2 to a validated broad-spectrum and potent prophylaxis

Screening for hyper-potent shRNA against SARS-CoV-2 We parsed the SARS-CoV-2 genome into a series of potential short hairpin RNA (shRNA) targets (Supplemental Fig. 1). This process was conducted by tiling the genome with overlapping 50 nucleotide-long sequences, each shifted by a single nucleotide from the other. The region targeted by each…

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ADC Therapeutics : Annual Report – Form 6-K

ADC Therapeutics SA 2022 Annual Report Table of Contents Letter to Shareholders Business Update Financial Review Corporate Governance Report from the Auditor on the Consolidated IFRS Financial Statements Consolidated IFRS Financial Statements for the Year Ended December 31, 2022 Report from the Auditor on the Statutory Financial Statements of ADC…

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New therapy for prevention and treatment of COVID-19

ExeVir Bio, and its scientific founders at Belgium’s VIB, Flanders’ leading life sciences institute, have published a pre-print paper by De Cae et al., entitled “Ultrapotent SARS coronavirus-neutralizing single-domain antibodies that bind a conserved membrane-proximal epitope of the spike.”  Nearly all SARS-CoV-2 neutralizing antibodies used in the clinic show substantial…

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Analysis of sequence diversity in Plasmodium falciparum glutamic acid-rich protein (PfGARP), an asexual blood stage vaccine candidate

Genetic diversity and structural organization of PfGARP The PfGARP sequences were successfully obtained from all 80 isolates which revealed clear and non-superposed signals on electropherograms. Size variation in PfGARP was observed among Thai isolates, ranging from 2179 to 2284 bp. In total, 26 alleles of PfGARP were identified among Thai isolates…

Continue Reading Analysis of sequence diversity in Plasmodium falciparum glutamic acid-rich protein (PfGARP), an asexual blood stage vaccine candidate

Hydroxychloroquine is metabolized by CYP2D6, CYP3A4, and CYP2C8, and inhibits CYP2D6, while its metabolites also inhibit CYP3A in vitro

Abstract This study aimed to explore the cytochrome P450 (CYP) metabolic and inhibitory profile of hydroxychloroquine (HCQ). Hydroxychloroquine metabolism was studied using human liver microsomes (HLMs) and recombinant CYP enzymes. The inhibitory effects of HCQ and its metabolites on nine CYPs were also determined in HLMs, using an automated substrate…

Continue Reading Hydroxychloroquine is metabolized by CYP2D6, CYP3A4, and CYP2C8, and inhibits CYP2D6, while its metabolites also inhibit CYP3A in vitro

Engineering protein glycosylation in CHO cells to be highly similar to murine host cells

1 Introduction Recombinant therapeutic proteins, also known as biologics, have been successfully used to treat a wide range of diseases, including cancers, inflammatory disorders, and cardiovascular diseases (Walsh, 2018). Biosimilars with comparable efficacy and safety profiles have emerged as alternative options to innovator therapies. A biosimilar is a biologic that…

Continue Reading Engineering protein glycosylation in CHO cells to be highly similar to murine host cells

Bioinformatics construction and experimental validation of a cuproptosis-related lncRNA prognostic model in lung adenocarcinoma for immunotherapy response prediction

Data collection and processing The RNA-sequencing data, clinical information and simple nucleotide variation of LUAD patients were retrieved from TCGA database (portal.gdc.cancer.gov/, accessed April 8, 2022). Nineteen cuproptosis-related genes (CRG) were mainly collected from previous study, including LIPT1, GLS, NFE2L2, NLRP3, LIAS, ATP7B, ATP7A, SLC31A1, FDX1, LIPT2, DLD, DLAT, PDHA1,…

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SLC7A11 is a prognostic biomarker in UCEC

Introduction Endometrial cancer (EC) is one of the most frequently diagnosed types of gynecological cancers, second only to cervical cancer in incidence.1 More than 50,000 women die from EC worldwide each year.2 Despite the development of diagnostic techniques and treatment means, the prognosis of advanced EC remains unsatisfactory.3,4 The therapeutic…

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Puerarin Suppresses Glycolysis and Increases Cisplatin Chemosensitivity in Oral Squamous Cell Carcinoma via FBXW7/mTOR Signaling

This study aimed to observe the effects of puerarin on glycolysis and cisplatin sensitivity in oral squamous cell carcinoma (oSCC) cells and to explore the underlying mechanisms. CAL27 cells over- or under-expressing FBXW7 were treated with cisplatin or puerarin, and the levels of proteins involved in glycolysis as well as…

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First Application of AlphaFold in Identifying Potential Liver Cancer Drug

Of the thousands of diseases that affect humans, treatments exist for only a handful. This lack of available therapeutics and efficiency in drug discovery and development processes is poised for transformation with the advent of artificial intelligence (AI). AlphaFold’s phenomenal success in predicting protein structures for the entire human genome…

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SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis

CDKs support SARS-CoV-2 RdRp-mediated gene expression To identify cellular proteins that modulate the SARS-CoV-2 RNA synthesis, we first performed immunoprecipitation coupled with mass spectrometry (MS) to determine cellular proteins that associate with SARS-CoV-2 RdRp. Briefly, Flag-tagged nsp7, Flag-tagged nsp8, and Flag-tagged nsp12 plasmids were co-transfected into HEK293T cells, and the…

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Mechano-Cas12a Assisted Tension Sensor (MCATS) for Massively Amplified Cell Traction Force Measurements

Abstract Cells transmit piconewton forces to mediate essential biological processes such as coagulation. One challenge is that cell-generated forces are infrequent, transient, and difficult to detect. Here, we report the development of Mechano-Cas12a Assisted Tension Sensor (MCATS) that utilizes CRISPR-Cas12a to transduce and amplify the molecular forces generated by cells….

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An Examination of IC50 and IC50-Shift Experiments in Assessing Time-Dependent Inhibition of CYP3A4, CYP2D6 and CYP2C9 in Human Liver Microsomes

Title: An Examination of IC50 and IC50-Shift Experiments in Assessing Time-Dependent Inhibition of CYP3A4, CYP2D6 and CYP2C9 in Human Liver Microsomes Volume: 2 Issue: 1 Author(s): Loren M. Berry and Zhiyang Zhao Affiliation: Keywords: Cytochrome P450, drug interactions, in vitro models, inhibition, microsomes, time-dependent inactivation Abstract: The relationship between time-dependent…

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Proscillaridin A induces mitochondrial damage and autophagy in pancreatic cancer and reduces the stability of SMAD4 in Panc-1 cells – Hou

Introduction Pancreatic cancer (PC) is one of the most aggressive and lethal cancers (1). Previous studies have shown that aging, environmental and behavioral changes are more closely related to the dramatic increase in the incidence of PC worldwide than genetic factors (2–5). A position paper published by the European Federation…

Continue Reading Proscillaridin A induces mitochondrial damage and autophagy in pancreatic cancer and reduces the stability of SMAD4 in Panc-1 cells – Hou

Uracil-DNA Glycosylase Assay by Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry Analysis

A non-labeled, non-radio-isotopic method to assay uracil-DNA glycosylase activity was developed using MALDI-TOF mass spectrometry for direct apurinic/apyrimidinic site-containing product analysis. The assay proved to be quite simple, specific, rapid, and easy to use for DNA glycosylase measurement. DNA repair mechanisms are very important for maintaining genome integrity in all…

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can one predict variable using scikit-learn rather binary classification if yes than how

Yes, this is a regression problem. There are many different models to solve a regression problem, from a simple Linear Regression, to Support Vector Regression or Decision Tree Regressors (and many more). They work similarly to binary classifier: You give them your training data and instead of 0/1 labels you…

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A hypoxia-related signature in lung squamous cell carcinoma

Introduction Lung cancer is the major leading cause of tumour-related deaths throughout the world, while lung squamous cell carcinoma (LUSC) as the second most common histological type of lung cancer.1 Each year, almost 1.8 million people are diagnosed with lung cancer worldwide and 400,000 of these die from LUSC.2,3 Due to…

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Innovative site-specific anti-HER2 antibody-drug conjugate

Introduction Antibody-drug conjugates (ADCs) have been studied for decades as a promising cancer treatment. As compared to conventional chemotherapy, ADCs have a larger therapeutic window because of their ability to target antigen-expressing tumor cells.1 As ADC drug development technology continues to evolve, several ADC drugs are being introduced to the…

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SUPPRESSION OF DIALYSIS PATIENTS’ LYMPHOCYTE IL-2R EXPRESSION BY GLUCOCORTICOIDS AND CYCLOSPORINE

Previous studies have shown interindividual heterogeneity in the suppressive effects of glucocorticoids and cyclosporine (CsA) on the proliferation responses of dialysis patients’ peripheral blood mononuclear cells (PBMC). In addition, methylprednisolone (MP) was shown to be significantly more suppressive than prednisolone (P), and PBMC from patients on peritoneal dialysis (PD) were…

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Establishment of sunitinib-resistant CDX model of ccRCC

Introduction Renal cell carcinoma (RCC) accounts for approximately 2–3% of all malignant tumors, and its prevalence is rising. Metastatic RCC accounts for 25–30% of all RCC cases, and has an exceedingly poor prognosis.1 In 2020, among approximately 430,000 newly discovered cases of RCC, 179,000 died.2 Clear cell renal cell carcinoma…

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GitHub – MD-Anderson-Bioinformatics/EGFR-Structure-Function-Nature-Manuscript

These files contain the source data and code used for the analyses included in the publication Robichaux et al 2021, “Structure-based classification predicts drug response in EGFR mutant NSCLC” These files will be made public at the time of acceptance.The files include but are not limited to: Summary of EGFR…

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Bacterial endosymbionts protect beneficial soil fungus from nematode attack

A healthy soil nourishes plants and animals, purifies water and air, and promotes sustainable agriculture. Characteristic for highly complex and competitive soil ecosystems are the frequent and direct interactions between all soil-dwelling microorganisms, animals, and plants (1, 2), all of which need to be provided with minerals and carbon sources….

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