DNA-guided transcription factor cooperativity shapes face and limb mesenchyme.

Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although in vitro studies suggest that it may be common, examples of such cooperativity remain scarce in cellular contexts.

Study of the Antibacterial Activity of Superhydrophilic and Superhydrophobic Copper Substrates against Multi-Drug-Resistant Hospital-Acquired Isolates.

The global spread of multidrug-resistant (MDR) hospital-acquired pathogens is a serious problem for healthcare units. The challenge of the spreading of nosocomial infections, also known as hospital-acquired pathogens, including Pseudomonas aeruginosa, must be addressed not only by developing effective drugs, but also by improving preventive measures in hospitals, such as passive bactericidal coatings deposited onto the touch surfaces. In this paper, we studied the antibacterial activity of superhydrophilic and superhydrophobic copper surfaces against the strain PA103 and its four different polyresistant clinical isolates with MDR.

DNA-guided transcription factor cooperativity shapes face and limb mesenchyme.

Transcription factors (TFs) can define distinct cellular identities despite nearly identical DNA-binding specificities. One mechanism for achieving regulatory specificity is DNA-guided TF cooperativity. Although studies suggest it may be common, examples of such cooperativity remain scarce in cellular contexts.

Fluorothiazinon inhibits the virulence factors of uropathogenic Escherichia coli involved in the development of urinary tract infection.

Uropathogenic Escherichia coli (UPEC) is the most common pathogenic bacterium associated with urinary tract infection. Due to the development of antibiotic resistance and MDR, UPEC infection has become a serious problem in the last decade. In order to combat resistance, it is necessary to develop innovative antimicrobial agents that act by different mechanisms than conventional antibiotics.

Preventative treatment with Fluorothiazinon suppressed Acinetobacter baumannii-associated septicemia in mice.

The high prevalence of multidrug-resistant Acinetobacter baumannii has emerged as a serious problem in the treatment of nosocomial infections in the past three decades. Recently, we developed a new small-molecule inhibitor belonging to a class of 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones, Fluorothiazinon (FT, previously called CL-55). FT effectively suppressed the T3SS of Chlamydia spp.

Structural insights into the interaction between transcription factors and the nucleosome.

In eukaryotic cells, DNA interacts with two main types of binding proteins: transcription factors and histones. Histones form the core of nucleosomes and display weak sequence preference owing to differences in bendability of different DNA sequences. By contrast, the affinity of transcription factors is highly dependent on DNA sequence - all sequences are bound with moderate affinity, but only few specific sequences are bound more tightly via molecular recognition of the DNA bases.

Second career of a biosynthetic enzyme: Lumazine synthase as a virus-like nanoparticle in vaccine development.

Naturally occurring and computationally designed protein cages can now be considered as extremely suitable materials for new developments in nanotechnology. Via self-assembly from single identical or non-identical protomers large oligomeric particles can be formed. Virus-like particles have today found a number of quite successful applications in the development of new vaccines.

Binding specificities of human RNA-binding proteins toward structured and linear RNA sequences.

RNA-binding proteins (RBPs) regulate RNA metabolism at multiple levels by affecting splicing of nascent transcripts, RNA folding, base modification, transport, localization, translation, and stability. Despite their central role in RNA function, the RNA-binding specificities of most RBPs remain unknown or incompletely defined. To address this, we have assembled a genome-scale collection of RBPs and their RNA-binding domains (RBDs) and assessed their specificities using high-throughput RNA-SELEX (HTR-SELEX).

Novel TMEM173 Mutation and the Role of Disease Modifying Alleles.

Upon binding to pathogen or self-derived cytosolic nucleic acids cyclic GMP-AMP synthase (cGAS) triggers the production of cGAMP that further activates transmembrane protein STING. Upon activation STING translocates from ER via Golgi to vesicles. Monogenic STING gain-of-function mutations cause early-onset type I interferonopathy, with disease presentation ranging from fatal vasculopathy to mild chilblain lupus.

Lycopene presence in facial skin corneocytes and sebum and its association with circulating lycopene isomer profile: Effects of age and dietary supplementation.

Lycopene is a dietary antioxidant known to prevent skin photodamage. This study aimed to examine age-dependent presence of this carotenoid on the surface of the facial skin and in the serum as well as to measure the same parameters during supplementation with lycopene. Serum samples and samples from facial skin surface were obtained from 60 young (under 25 years old) and 60 middle-aged (over 50 years old) volunteers.

Impact of constitutional TET2 haploinsufficiency on molecular and clinical phenotype in humans.

Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression.

Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line.

In the present paper, we report that can be efficiently propagated and affect mRNA expression for two major cytokines, relevant to tumor progression, in CWR-R1 cells, a malignant prostate cell line. CWR-R1 and McCoy cells, a classic cell line for chlamydial research, were grown and infected with under similar conditions. Cell monolayers were harvested for RNA analysis and immunostaining with major outer membrane protein (MOMP) antibody at 24, 48, and 72 hours of the postinfection (hpi) period.

The interaction landscape between transcription factors and the nucleosome.

Nucleosomes cover most of the genome and are thought to be displaced by transcription factors in regions that direct gene expression. However, the modes of interaction between transcription factors and nucleosomal DNA remain largely unknown. Here we systematically explore interactions between the nucleosome and 220 transcription factors representing diverse structural families.

Association with Monoclonal Antibody Promotes Intracellular Delivery of Lycopene.

Incubation of B10.MLM cells, a cell line of alveolar macrophages, with lycopene, a carotenoid, leads to an increase of lycopene content in their microsomal fraction. That increase was higher and developed faster when the cells were incubated with immune complexes formed by lycopene and mAb 6B9 (L-6B9 mAb), a monoclonal hapten-specific antibody raised against lycopene, as compared with dimethyl sulfoxide (DMSO)-dissolved lycopene (DMSO-L).

Non-Invasive Immunofluorescence Assessment of Lycopene Supplementation Status in Skin Smears.

Circulating lycopene level is negatively associated with the prevalence of cardiovascular disease, cancers (prostate and breast), type 2 diabetes mellitus, and aging. Traditionally, lycopene is measured in biological specimens by a combination of high-performance liquid chromatography (HPLC) and mass spectrometry methods. Moreover, as we recently reported, tissue/cell lycopene depositions can be observed by the immunohistochemistry method with a newly developed monoclonal antibody (mAb) against lycopene.

Two distinct DNA sequences recognized by transcription factors represent enthalpy and entropy optima.

Most transcription factors (TFs) can bind to a population of sequences closely related to a single optimal site. However, some TFs can bind to two distinct sequences that represent two local optima in the Gibbs free energy of binding (ΔG). To determine the molecular mechanism behind this effect, we solved the structures of human HOXB13 and CDX2 bound to their two optimal DNA sequences, CAATAAA and TCGTAAA.

Resveratrol Inhibits Propagation of in McCoy Cells.

Resveratrol (RESV), an antifungal compound from grapes and other plants, has a distinct ability to inhibit the developmental cycle in McCoy cells, a classic cell line used for chlamydial research. Inoculation of with increasing amounts of RESV (from 12.5 to 100 M) gave a dose-dependent reduction in the number of infected McCoy cells visualized by using monoclonal antibodies against chlamydial lipopolysaccharide.

[Single-domain adapted antibodies against Chlamydia trachomatis, preserving the development of chlamidic infection in vitro].

The technology for the generating of single-domain recombinant monoclonal antibodies (nanoantibodies) based on the immunization of a camel, cloning of induced sequences encoding single-domain antigen-recognizing fragments of non-canonical camel antibodies, as well as functional selection of clones of nanoantibodies by the phage display method, was used to obtain new effective tools for more efficient diagnostics of Chlamydia infection and to develop new approaches for effective therapy. Two promising nanoantibodies were obtained. They showed effective binding to extracellular and intracellular forms of C.

Lycopene Inhibits Propagation of Chlamydia Infection.

Chlamydiaceae is a family of obligate intracellular pathogenic bacteria with similar developmental cycles and cell biology responsible for a wide range of diseases in different hosts including genital and eye inflammatory diseases, arthritis, and inflammatory diseases of the respiratory and cardiovascular systems. In the present paper, we report that lycopene, one of the main dietary carotenoids, which is present in tomato and some other fruits, has a strong inhibitory effect on and infections in alveolar macrophages. This finding was documented by both immunofluorescence analysis and electron microscopy.

Impact of cytosine methylation on DNA binding specificities of human transcription factors.

The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences.

Generation and Application of Monoclonal Antibody Against Lycopene.

A monoclonal antibody (Mab) against lycopene was developed from hybridoma clones obtained from BALB/c mice immunized with trans-isomer of lycopene (t-lycopene, t-LC) conjugated with colloidal gold particles. An alternating immunization schedule which included injection of both formulations of immunogen (without and with Freund's adjuvant) was most effective in the elucidation of a measurable immune response to the t-Lycopene conjugate. Selected hybridoma clones were able to produce an Mab positive in competition assay.

Structural perspective of cooperative transcription factor binding.

In prokaryotes, individual transcription factors (TFs) can recognize long DNA motifs that are alone sufficient to define the genes that they induce or repress. In contrast, in higher organisms that have larger genomes, TFs recognize sequences that are too short to define unique genomic positions. In addition, development of multicellular organisms requires molecular systems that are capable of executing combinatorial logical operations.

Damaging heterozygous mutations in NFKB1 lead to diverse immunologic phenotypes.

Background: The nuclear factor κ light-chain enhancer of activated B cells (NF-κB) signaling pathway is a key regulator of immune responses. Accordingly, mutations in several NF-κB pathway genes cause immunodeficiency.

Objective: We sought to identify the cause of disease in 3 unrelated Finnish kindreds with variable symptoms of immunodeficiency and autoinflammation.

Structural insights into the DNA-binding specificity of E2F family transcription factors.

The mammalian cell cycle is controlled by the E2F family of transcription factors. Typical E2Fs bind to DNA as heterodimers with the related dimerization partner (DP) proteins, whereas the atypical E2Fs, E2F7 and E2F8 contain two DNA-binding domains (DBDs) and act as repressors. To understand the mechanism of repression, we have resolved the structure of E2F8 in complex with DNA at atomic resolution.