IQGAP3 Is an Important Mediator of Skin Inflammatory Diseases.

IQGAP3 (IQ Motif Containing GTPase Activating Protein 3) is member of the IQGAP family of scaffold proteins, which are essential for assembling multiprotein complexes that coordinate various intracellular signaling pathways. Previous research has shown that is overexpressed in psoriatic skin lesions. Given its involvement in processes like cell proliferation and chemokine signaling, we sought to explore its molecular role in driving the psoriatic phenotype of keratinocytes.

Tumor Organoids: The Era of Personalized Medicine.

The strategies of future medicine are aimed to modernize and integrate quality approaches including early molecular-genetic profiling, identification of new therapeutic targets and adapting design for clinical trials, personalized drug screening (PDS) to help predict and individualize patient treatment regimens. In the past decade, organoid models have emerged as an innovative in vitro platform with the potential to realize the concept of patient-centered medicine. Organoids are spatially restricted three-dimensional clusters of cells ex vivo that self-organize into complex functional structures through genetically programmed determination, which is crucial for reconstructing the architecture of the primary tissue and organs.

Using an RNA Aptamer to Inhibit the Action of Effector Proteins of Plant Pathogens.

In previous work, we experimentally demonstrated the possibility of using RNA aptamers to inhibit endogenous protein expression and their function within plant cells In the current work, we show that our proposed method is suitable for inhibiting the functions of exogenous, foreign proteins delivered into the plant via various mechanisms, including pathogen proteins. Stringent experimentation produced robust RNA aptamers that are able to bind to the recombinant HopU1 effector protein of bacteria. This research uses genetic engineering methods to constitutively express/transcribe HopU1 RNA aptamers in transgenic .

Visualizing the Nucleome Using the CRISPR-Cas9 System: From in vitro to in vivo.

One of the latest methods in modern molecular biology is labeling genomic loci in living cells using fluorescently labeled Cas protein. The NIH Foundation has made the mapping of the 4D nucleome (the three-dimensional nucleome on a timescale) a priority in the studies aimed to improve our understanding of chromatin organization. Fluorescent methods based on CRISPR-Cas are a significant step forward in visualization of genomic loci in living cells.

Heterogeneous Distribution of Phospholipid Molecular Species in the Surface Culture of : New Facts about Lipids Containing α-Linolenic Fatty Acid.

Mycelial fungi grow as colonies consisting of polar growing hyphae, developing radially from spore or inoculum. Over time, the colony develops, hyphae are subject to various exogenous or endogenous stimuli, and mycelium becomes heterogeneous in growth, gene expression, biosynthesis, and secretion of proteins and metabolites. Although the biochemical and molecular mechanisms of mycelium heterogeneity have been the subject of many studies, the role of lipids in colony development and zonality is still not understood.

Recent selection of candidate genes for mammal domestication in Europeans and language change in Europe: a hypothesis.

Background And Aim: Human evolution resulted from changes in our biology, behaviour, and culture. One source of these changes has been hypothesised to be our self-domestication (that is, the development in humans of features commonly found in domesticated strains of mammals, seemingly as a result of selection for reduced aggression). Signals of domestication, notably brain size reduction, have increased in recent times.

New ancient Eastern European genomes illuminate the dispersal of plague in Europe.

, the causative agent of plague, has been prevalent among humans for at least 5000 years, being accountable for several devastating epidemics in history, including the Black Death. Analyses of the genetic diversity of ancient strains of have shed light on the mechanisms of evolution and the spread of plague in Europe. However, many questions regarding the origins of the pathogen and its long persistence in Europe are still unresolved, especially during the late medieval time period.

RNA-aptamers-As targeted inhibitors of protein functions in plants.

The scope of RNA-aptamers application is becoming wider and has expanded beyond solely medical use. We propose the use of RNA-aptamers in plants to suppress the functions of individual proteins, thereby achieving resistance to various biotic and abiotic stresses. In current work we experimentally demonstrate the possibility of inhibiting protein activity in N.

FRA1 mediates the activation of keratinocytes: Implications for the development of psoriatic plaques.

In this study we investigated the role of FRA1, a transcription factor from the AP-1 family, in the regulation of keratinocyte characteristics important for the development of psoriatic plaques. FRA1 is characterized by elevated expression in the skin of psoriasis patients, thus leading us to predict it to be one of the major regulators of keratinocyte phenotype during the development of psoriatic lesions. Pathway analysis of RNAseq data allowed us to identify FRA1-mediated signaling cascades leading to the manifestation of the most prominent skin characteristics of the disease: the development of inflammation, epithelial-mesenchymal transition, activation of metalloproteases, and keratinocyte proliferation and migration.

Search for Partner Proteins of Immunophilins Involved in the Control of Plant Immunity.

The involvement of plant immunophilins in multiple essential processes such as development, various ways of adapting to biotic and abiotic stresses, and photosynthesis has already been established. Previously, research has demonstrated the involvement of three immunophilin genes (, , and ) in the control of plant response to invasion by various pathogens. Current research attempts to identify host target proteins for each of the selected immunophilins.

Familial Esophageal Squamous Cell Carcinoma with damaging rare/germline mutations in KCNJ12/KCNJ18 and GPRIN2 genes.

In Iran, esophageal cancer is the fourth common cancers in women and sixth common cancers in men. Here we evaluated the importance of familial risk factors and the role of genetic predisposition in Esophageal Squamous Cell Carcinoma (ESCC) using Whole-Exome Sequencing (WES). Germline damaging mutations were identified in WES data from 9 probands of 9 unrelated ESCC pedigrees.

Identification of Transcriptional Regulators of Psoriasis from RNA-Seq Experiments.

Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the molecular mechanisms of regulation of the disease we performed RNA sequencing (RNA-Seq) analysis of 14 pairs of skin samples collected from psoriatic patients. Subsequent pathway analysis and an extraction of transcriptional regulators governing psoriasis-associated pathways was executed using a combination of MetaCore Interactome enrichment tool and cisExpress algorithm, and followed by comparison to a set of previously described psoriasis response elements.

Integrated computational approach to the analysis of RNA-seq data reveals new transcriptional regulators of psoriasis.

Psoriasis is a common inflammatory skin disease with complex etiology and chronic progression. To provide novel insights into the regulatory molecular mechanisms of the disease, we performed RNA sequencing analysis of 14 pairs of skin samples collected from patients with psoriasis. Subsequent pathway analysis and extraction of the transcriptional regulators governing psoriasis-associated pathways was executed using a combination of the MetaCore Interactome enrichment tool and the cisExpress algorithm, followed by comparison to a set of previously described psoriasis response elements.

Nucleotide diversity analysis highlights functionally important genomic regions.

We analyzed functionality and relative distribution of genetic variants across the complete Oryza sativa genome, using the 40 million single nucleotide polymorphisms (SNPs) dataset from the 3,000 Rice Genomes Project (http://snp-seek.irri.org), the largest and highest density SNP collection for any higher plant.

Toward high-resolution population genomics using archaeological samples.

The term 'ancient DNA' (aDNA) is coming of age, with over 1,200 hits in the PubMed database, beginning in the early 1980s with the studies of 'molecular paleontology'. Rooted in cloning and limited sequencing of DNA from ancient remains during the pre-PCR era, the field has made incredible progress since the introduction of PCR and next-generation sequencing. Over the last decade, aDNA analysis ushered in a new era in genomics and became the method of choice for reconstructing the history of organisms, their biogeography, and migration routes, with applications in evolutionary biology, population genetics, archaeogenetics, paleo-epidemiology, and many other areas.

Laccase multigene families in Agaricomycetes.

Here we present the results of the exploration of laccase multigene families (MGFs) in basidiomycetous fungi from different taxonomic groups using a next generation sequencing (NGS) technology. In our study, multiple laccase genes were identified in all of the investigated fungi (13 species) from Polyporaceae, Phanerochaetaceae, Meruliaceae, Pleurotaceae, Physalacriaceae, and Peniophoraceae families. It was shown that phylogenetic positioning of the newly identified sequences exhibit patterns of clusterization with respect to enzyme properties.

Diacylglyceryltrimethylhomoserine content and gene expression changes triggered by phosphate deprivation in the mycelium of the basidiomycete Flammulina velutipes.

Diacylglyceryltrimethylhomoserines (DGTS) are betaine-type lipids that are phosphate-free analogs of phosphatidylcholines (PC). DGTS are abundant in some bacteria, algae, primitive vascular plants and fungi. In this study, we report inorganic phosphate (Pi) deficiency-induced DGTS synthesis in the basidial fungus Flammulina velutipes (Curt.

Three-dimensional skin models of psoriasis.

Three-dimensional models of psoriatic skin occupy an intermediate position between cell cultures and animal-based models. Unlike cultured cells, they closely imitate changes in cell differentiation and metabolism, which are characteristic of psoriatic lesional skin. Because 3-dimensional models exclude nonspecific influences of the surrounding organs and tissues, in some studies they are preferred over animal-based models.

Distance-based classifiers as potential diagnostic and prediction tools for human diseases.

Typically, gene expression biomarkers are being discovered in course of high-throughput experiments, for example, RNAseq or microarray profiling. Analytic pipelines that extract so-called signatures suffer from the "Dimensionality curse": the number of genes expressed exceeds the number of patients we can enroll in the study and use to train the discriminator algorithm. Hence, problems with the reproducibility of gene signatures are more common than not; when the algorithm is executed using a different training set, the resulting diagnostic signature may turn out to be completely different.

Matrix metalloproteinases and their role in psoriasis.

This review summarizes the contribution of matrix metalloproteinases to the pathogenesis of psoriasis. In psoriasis, matrix metalloproteinases are involved in the structural changes of the epidermis via the modification of intracellular contacts and the composition of the extracellular matrix, promoting angiogenesis in the dermal blood vessels and the infiltration of immune cells. Moreover, some matrix metalloproteinases become differentially expressed during the disease eruption and their expression correlates with the clinical score.

Characterization of three Arabidopsis thaliana immunophilin genes involved in the plant defense response against Pseudomonas syringae.

Plant immunophilins are a broadly conserved family of proteins, which carry out a variety of cellular functions. In this study, we investigated three immunophilin genes involved in the Arabidopsis thaliana response to Pseudomonas syringae infection: a cytoplasmic localized AtCYP19, a cytoplasmic and nuclear localized AtCYP57, and one nucleus directed FKBP known as AtFKBP65. Arabidopsis knock-out mutations in these immunophilins result in an increased susceptibility to P.

Integrated network analysis of transcriptomic and proteomic data in psoriasis.

Background: Psoriasis is complex inflammatory skin pathology of autoimmune origin. Several cell types are perturbed in this pathology, and underlying signaling events are complex and still poorly understood.

Results: In order to gain insight into molecular machinery underlying the disease, we conducted a comprehensive meta-analysis of proteomics and transcriptomics of psoriatic lesions from independent studies.

Bacterial thermostable beta-glucanases as a tool for plant functional genomics.

A new strategy for creating experimental models for functional genomics has been proposed. It is based on the expression in transgenic plants of genes from thermophilic bacteria encoding functional analogues of plant proteins with high specific activity and thermal stability. We have validated this strategy by comparing physiological, biochemical and molecular properties of control tobacco plants and transgenic plants expressing genes of beta-glucanases with different substrate specificity.