The oncogenic fusion protein EML4-NTRK3 requires three salt bridges for stability and biological activity.

Aim Of Study: Chromosomal translocations involving neurotrophic receptor tyrosine kinases (NTRKs) have been identified in 20 % of soft tissue sarcomas. This work focuses on the EML4-NTRK3 translocation identified in cases of Infantile Fibrosarcoma, which contains the coiled-coil multimerization domain of Echinoderm Microtubule-like protein 4 (EML4) fused with the tyrosine kinase domain of Neurotrophic Receptor Tyrosine Kinase 3 (NTRK3). The aim of the study was to test the importance of tyrosine kinase activity and multimerization for the oncogenic activity of EML4-NTRK3.

Critical domains for NACC2-NTRK2 fusion protein activation.

Neurotrophic receptor tyrosine kinases (NTRKs) belong to the receptor tyrosine kinase (RTK) family. NTRKs are responsible for the activation of multiple downstream signaling pathways that regulate cell growth, proliferation, differentiation, and apoptosis. NTRK-associated mutations often result in oncogenesis and lead to aberrant activation of downstream signaling pathways including MAPK, JAK/STAT, and PLCγ1.

Oncogenic driver FGFR3-TACC3 requires five coiled-coil heptads for activation and disulfide bond formation for stability.

FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers; these were analyzed to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein. While TACC3 exons 11 and 12 are dispensable for activity, our results show that FGFR3-TACC3 requires exons 13-16 for biological activity.

Proteomic analysis reveals dual requirement for Grb2 and PLCγ1 interactions for BCR-FGFR1-Driven 8p11 cell proliferation.

Translocation of Fibroblast Growth Factor Receptors (FGFRs) often leads to aberrant cell proliferation and cancer. The BCR-FGFR1 fusion protein, created by chromosomal translocation t(8;22)(p11;q11), contains Breakpoint Cluster Region (BCR) joined to Fibroblast Growth Factor Receptor 1 (FGFR1). BCR-FGFR1 represents a significant driver of 8p11 myeloproliferative syndrome, or stem cell leukemia/lymphoma, which progresses to acute myeloid leukemia or T-cell lymphoblastic leukemia/lymphoma.

Fibroblast growth factor receptor 4 promotes glioblastoma progression: a central role of integrin-mediated cell invasiveness.

Glioblastoma (GBM) is characterized by a particularly invasive phenotype, supported by oncogenic signals from the fibroblast growth factor (FGF)/ FGF receptor (FGFR) network. However, a possible role of FGFR4 remained elusive so far. Several transcriptomic glioma datasets were analyzed.

Satellite data track spatial and temporal declines in European beech forest canopy characteristics associated with intense drought events in the Rhön Biosphere Reserve, central Germany.

The increasing intensity and frequency of droughts under climate change demands effective ways to monitor drought impacts. We sought to determine how different satellite remote sensing sources influence our ability to identify temporal and spatial impacts on European beech forest canopy health during intense drought events. Imagery from three satellite series (MODIS, Landsat and Sentinel-2) was used to observe changes in canopy health during the intense droughts of 2003 and 2018 in the Rhön Biosphere Reserve, central Germany.

Construction and evaluation of a bioluminescent reporter for use in preservative efficacy testing.

Preservative efficacy testing (PET) is a fundamental practice in industrial microbiology used to ensure product shelf-life and quality. To improve on current growth-based PET, bioluminescence was evaluated as a real-time bacterial viability indicator using . Random mutagenesis of an industrial strain with a promoter-less mini-Tn5 was used to select a stable reporter (LUX12H5) with an un-altered growth and preservative susceptibility phenotype.

Characterization of FGFR signaling in prostate cancer stem cells and inhibition via TKI treatment.

Metastatic castrate-resistant prostate cancer (CRPC) remains uncurable and novel therapies are needed to better treat patients. Aberrant Fibroblast Growth Factor Receptor (FGFR) signaling has been implicated in advanced prostate cancer (PCa), and FGFR1 is suggested to be a promising therapeutic target along with current androgen deprivation therapy. We established a novel 3D culture system to study endogenous FGFR signaling in a rare subpopulation of prostate cancer stem cells (CSCs) in the cell lines PC3, DU145, LNCaP, and the induced pluripotent iPS87 cell line.

Typical achondroplasia secondary to a unique insertional variant of FGFR3 with in vitro demonstration of its effect on FGFR3 function.

We describe an individual in whom clinical and radiographic features are typical for achondroplasia, but in whom the common variants of FGFR3 that result in achondroplasia are absent. Whole exome sequencing demonstrated a novel, de novo 6 base pair tandem duplication in FGFR3 that results in the insertion of Ser-Phe after position Leu324. in vitro studies showed that this variant results in aberrant dimerization, excessive spontaneous phosphorylation of FGFR3 dimers and excessive, ligand-independent tyrosine kinase activity.

Carvacrol attenuates Campylobacter jejuni colonization factors and proteome critical for persistence in the chicken gut.

Campylobacter jejuni is a major foodborne pathogen that causes gastroenteritis in humans. Chickens act as the reservoir host for C. jejuni, wherein the pathogen asymptomatically colonizes the ceca leading to contamination of carcasses during slaughter.

Oncogenic fusion protein FGFR2-PPHLN1: Requirements for biological activation, and efficacy of inhibitors.

Aim Of Study: Chromosomal translocations such as t(10;12)(q26,q12) are associated with intrahepatic cholangiocarcinoma, a universally fatal category of liver cancer. This translocation creates the oncogenic fusion protein of Fibroblast Growth Factor Receptor 2 joined to Periphilin 1. The aims of this study were to identify significant features required for biological activation, analyze the activation of downstream signaling pathways, and examine the efficacy of the TKIs BGJ398 and TAS-120, and of the MEK inhibitor Trametinib.

Characterization of iPS87, a prostate cancer stem cell-like cell line.

Prostate cancer affects hundreds of thousands of men and families throughout the world. Although chemotherapy, radiation, surgery, and androgen deprivation therapy are applied, these therapies do not cure metastatic prostate cancer. Patients treated by androgen deprivation often develop castration resistant prostate cancer which is incurable.

Draft Genome Sequences of Campylobacter jejuni Strains Isolated from Poultry.

Four wild-type strains isolated from the cecal contents of broiler chickens were sequenced. The average genome size was 1,622,170 bp, with 1,667 to 1,761 coding sequences and 47 to 51 RNAs. Multiple genes encoding motility, intestinal colonization, toxin production, stress tolerance, and multidrug resistance were present in all the strains.

Functions of FGFR2 corrupted by translocations in intrahepatic cholangiocarcinoma.

Cholangiocarcinoma, originating from the biliary duct, represents a subset of liver cancer. With about 8000 new cases of cholangiocarcinoma diagnosed annually in the U.S.

-Cinnamaldehyde, Eugenol and Carvacrol Reduce Biofilms and Modulate Expression of Select Genes and Proteins.

is the leading cause of human foodborne illness globally, and is strongly linked with the consumption of contaminated poultry products. Several studies have shown that can form sanitizer tolerant biofilm leading to product contamination, however, limited research has been conducted to develop effective control strategies against biofilms. This study investigated the efficacy of three generally recognized as safe status phytochemicals namely, -cinnamaldehyde (TC), eugenol (EG), or carvacrol (CR) in inhibiting biofilm formation and inactivating mature biofilm on common food contact surfaces at 20 and 37°C.

Oncogenic fusion protein BCR-FGFR1 requires the breakpoint cluster region-mediated oligomerization and chaperonin Hsp90 for activation.

Mutation and translocation of fibroblast growth factor receptors often lead to aberrant signaling and cancer. This work focuses on the t(8;22)(p11;q11) chromosomal translocation which creates the breakpoint cluster region (BCR) fibroblast growth factor receptor1 (FGFR1) (BCR-FGFR1) fusion protein. This fusion occurs in stem cell leukemia/lymphoma, which can progress to atypical chronic myeloid leukemia, acute myeloid leukemia, or B-cell lymphoma.

Effects of Animal-Assisted Activity on Mood States and Feelings in a Psychiatric Setting.

Research has shown that animal-assisted activity (AAA) effectively improves physiological, psychological, emotional, and social well-being in various environments. To identify how AAA affects mood states and feelings among both patients and staff on inpatient psychiatric units. This study used a quasi-experimental, pre-/posttest design with nonequivalent comparison groups.

Not all Pseudomonas aeruginosa are equal: strains from industrial sources possess uniquely large multireplicon genomes.

Pseudomonas aeruginosa is a highly versatile, antibiotic-resistant Gram-negative bacterium known for causing opportunistic infections and contamination of industrial products. Despite extensive genomic analysis of clinical P. aeruginosa strains, no genomes exist for preservative-tolerant industrial strains.

BCR: a promiscuous fusion partner in hematopoietic disorders.

Considerable advances have been made in our understanding of the molecular basis of hematopoietic cancers. The discovery of the BCR-ABL fusion protein over 50 years ago has brought about a new era of therapeutic progress and overall improvement in patient care, mainly due to the development and use of personalized medicine and tyrosine kinase inhibitors (TKIs). However, since the detection of BCR-ABL, BCR has been identified as a commonly occurring fusion partner in hematopoietic disorders.

Carvacrol antimicrobial wash treatments reduce Campylobacter jejuni and aerobic bacteria on broiler chicken skin.

Campylobacter jejuni, a major cause of human gastroenteritis worldwide, is often associated with the consumption of contaminated poultry products. With increasing consumer preference to natural and minimally processed foods, interventions utilizing natural antimicrobials for controlling C. jejuni on poultry products are gaining popularity.

Edible Coatings Fortified With Carvacrol Reduce on Chicken Wingettes and Modulate Expression of Select Virulence Genes.

, a leading cause of foodborne disease in humans, associate primarily with consumption of contaminated poultry and poultry products. Intervention strategies aimed at reducing contamination on poultry products could significantly reduce infection in humans. This study evaluated the efficacy of gum arabic (GA) and chitosan (CH) fortified with carvacrol (CR) as an antimicrobial coating treatment for reducing on chicken wingettes.

Pectin or chitosan coating fortified with eugenol reduces Campylobacter jejuni on chicken wingettes and modulates expression of critical survival genes.

Campylobacter jejuni infection in humans is strongly associated with the consumption of contaminated poultry products. With increasing consumer demand for minimally processed and natural product, there is a need for novel intervention strategies for controlling C. jejuni.

Oncogenic driver FGFR3-TACC3 is dependent on membrane trafficking and ERK signaling.

Fusion proteins resulting from chromosomal translocations have been identified as oncogenic drivers in many cancers, allowing them to serve as potential drug targets in clinical practice. The genes encoding FGFRs, Fibroblast Growth Factor Receptors, are commonly involved in such translocations, with the FGFR3-TACC3 fusion protein frequently identified in many cancers, including glioblastoma, cervical cancer, bladder cancer, nasopharyngeal carcinoma, and lung adenocarcinoma among others. FGFR3-TACC3 retains the entire extracellular domain and most of the kinase domain of FGFR3, with its C-terminal domain fused to TACC3.

Oncogenic mutations in IKKβ function through global changes induced by K63-linked ubiquitination and result in autocrine stimulation.

Mutations at position K171 in the kinase activation loop of Inhibitor of κB kinase beta (IKKβ) occur in multiple myeloma, spleen marginal zone lymphoma and mantle cell lymphoma. Previously, we demonstrated that these result in constitutive kinase activation and stimulate Signal Transducer and Activator of Transcription 3 (STAT3). This work also identified K147 as a site of K63-linked regulatory ubiquitination required for activation of signaling pathways.