The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung.

Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs' stability and their long-term effects limit their implementation in clinical practice, including treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19. Here, we aimed to investigate the safety of intranasal application of human adipose tissue-derived MSCs in a preclinical experimental mice model and elucidate their effects on the lungs. We assessed short-term (two days) and long-term (nine days) effects of MSCs administration on lung morphology, immune responses, epithelial barrier function, and transcriptomic profiles. We observed an increased frequency of IFNγ- producing T cells and a decrease in occludin and claudin 3 as a long-term effect of MSCs administration. We also found changes in the lung transcriptomic profiles, reflecting redox imbalance and hypoxia signaling pathway. Additionally, we found dysregulation in genes clustered in pattern recognition receptors, macrophage activation, oxidative stress, and phagocytosis. Our results suggest that i.n. MSCs administration to noninflamed healthy lungs induces, in the late stages, low-grade inflammatory responses aiming at the clearance of MSCs graft.

Case report: Rare among ultrarare-Clinical odyssey of a new patient with Ogden syndrome.

Introduction: The definition of ultra-rare disease in terms of its prevalence varies between the sources, usually amounting to ca. 1 in 1.000.000 births. Nonetheless, there are even less frequent disorders, such as Ogden syndrome, which up to this day was diagnosed in less than 10 patients worldwide. They present typically with a variety of developmental defects, including postnatal growth retardation, psychomotor delay and hypotonia. This disorder is caused by the heterozygous mutations in NAA10 gene, which encodes N-alpha-acetyltransferase 10, involved in protein biosynthesis. Therefore, Ogden syndrome belongs to the broader group of genetic disorders, collectively described as NAA10-related syndrome. Case report: We present a case of a Polish male infant, born in 39. GW with c-section due to the pathological cardiotocography signal. Hypotrophy (2400 g) and facial dysmorphism were noted in the physical examination. From the first minute, the child required mechanical ventilation - a nasal continuous positive airway pressure. For the first 27 days, the patient was treated in a neonatal intensive care unit, where a series of examinations were conducted. On their basis, the presence of the following defects was determined: muscular ventricular septal defects, patent foramen ovale, pectus excavatum, clubfoot and axial hypotonia. Child was then consequently referred to the genetic clinic for counselling. Results of the tests allowed the diagnosis of Ogden syndrome. In the following months the patient's condition worsened due to the numerous pulmonary infections. Despite the advanced treatment including the variety of medications, the patient eventually died at the age of 10 months. Conclusion: This case report presents a tenth patient diagnosed with Ogden syndrome reported worldwide. It expands the morphologic and clinical phenotype, emphasizing the possible severity of pneumonological disorders in these patients, which may pose a greater threat to a child's life than more frequently described cardiovascular dysfunctions associated with this syndrome.

Insights into the Histone Acetylation-Mediated Regulation of the Transcription Factor Genes That Control the Embryogenic Transition in the Somatic Cells of Arabidopsis.

Somatic embryogenesis (SE), which is a process that involves the in vitro-induced embryogenic reprogramming of plant somatic cells, requires dynamic changes in the cell transcriptome. These changes are fine-tuned by many genetic and epigenetic factors, including posttranslational histone modifications such as histone acetylation. Antagonistically acting enzymes, histone acetyltransferases (HATs) and deacetylases (HDACs), which control histone acetylation in many developmental processes, are believed to control SE. However, the function of specific HAT/HDACs and the genes that are subjected to histone acetylation-mediated regulation during SE have yet to be revealed. Here, we present the global and gene-specific changes in histone acetylation in Arabidopsis explants that are undergoing SE. In the TSA (trichostatin A)-induced SE, we demonstrate that H3 and H4 acetylation might control the expression of the critical transcription factor (TF) genes of a vital role in SE, including LEC1, LEC2 (LEAFY COTYLEDON 1; 2), FUS3 (FUSCA 3) and MYB118 (MYB DOMAIN PROTEIN 118). Within the HATs and HDACs, which mainly positively regulate SE, we identified HDA19 as negatively affecting SE by regulating LEC1, LEC2 and BBM. Finally, we provide some evidence on the role of HDA19 in the histone acetylation-mediated regulation of LEC2 during SE. Our results reveal an essential function of histone acetylation in the epigenetic mechanisms that control the TF genes that play critical roles in the embryogenic reprogramming of plant somatic cells. The results implicate the complexity of Hac-related gene regulation in embryogenic induction and point to differences in the regulatory mechanisms that are involved in auxin- and TSA-induced SE.

Gut Microbiome in Chronic Coronary Syndrome Patients.

Despite knowledge of classical coronary artery disease (CAD) risk factors, the morbidity and mortality associated with this disease remain high. Therefore, new factors that may affect the development of CAD, such as the gut microbiome, are extensively investigated. This study aimed to evaluate gut microbiome composition in CAD patients in relation to the control group. We examined 169 CAD patients and 166 people in the control group, without CAD, matched in terms of age and sex to the study group. Both populations underwent a detailed health assessment. The microbiome analysis was based on the V3-V4 region of the 16S rRNA gene (NGS method). Among 4074 identified taxonomic units in the whole population, 1070 differed between study groups. The most common bacterial types were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Furthermore, a higher Firmicutes/Bacteroidetes ratio in the CAD group compared with the control was demonstrated. Firmicutes/Bacteroidetes ratio, independent of age, sex, CAD status, LDL cholesterol concentration, and statins treatment, was related to altered phosphatidylcholine concentrations obtained in targeted metabolomics. Altered alpha-biodiversity (Kruskal-Wallis test, p = 0.001) and beta-biodiversity (Bray-Curtis metric, p < 0.001) in the CAD group were observed. Moreover, a predicted functional analysis revealed some taxonomic units, metabolic pathways, and proteins that might be characteristic of the CAD patients' microbiome, such as increased expressions of 6-phospho-ß-glucosidase and protein-N(pi)-phosphohistidine-sugar phosphotransferase and decreased expressions of DNA topoisomerase, oxaloacetate decarboxylase, and 6-beta-glucosidase. In summary, CAD is associated with altered gut microbiome composition and function.

Aluminum or Low pH - Which Is the Bigger Enemy of Barley? Transcriptome Analysis of Barley Root Meristem Under Al and Low pH Stress.

Aluminum (Al) toxicity is considered to be the most harmful abiotic stress in acidic soils that today comprise more than 50% of the world's arable lands. Barley belongs to a group of crops that are most sensitive to Al in low pH soils. We present the RNA-seq analysis of root meristems of barley seedlings grown in hydroponics at optimal pH (6.0), low pH (4.0), and low pH with Al (10 µM of bioavailable Al3+ ions). Two independent experiments were conducted: with short-term (24 h) and long-term (7 days) Al treatment. In the short-term experiment, more genes were differentially expressed (DEGs) between root meristems grown at pH = 6.0 and pH = 4.0, than between those grown at pH = 4.0 with and without Al treatment. The genes upregulated by low pH were associated mainly with response to oxidative stress, cell wall organization, and iron ion binding. Among genes upregulated by Al, overrepresented were those related to response to stress condition and calcium ion binding. In the long-term experiment, the number of DEGs between hydroponics at pH = 4.0 and 6.0 were lower than in the short-term experiment, which suggests that plants partially adapted to the low pH. Interestingly, 7 days Al treatment caused massive changes in the transcriptome profile. Over 4,000 genes were upregulated and almost 2,000 genes were downregulated by long-term Al stress. These DEGs were related to stress response, cell wall development and metal ion transport. Based on our results we can assume that both, Al3+ ions and low pH are harmful to barley plants. Additionally, we phenotyped the root system of barley seedlings grown in the same hydroponic conditions for 7 days at pH = 6.0, pH = 4.0, and pH = 4.0 with Al. The results correspond to transcriptomic data and show that low pH itself is a stress factor that causes a significant reduction of root growth and the addition of aluminum further increases this reduction. It should be noted that in acidic arable lands, plants are exposed simultaneously to both of these stresses. The presented transcriptome analysis may help to find potential targets for breeding barley plants that are more tolerant to such conditions.

DNA Demethylation in Response to Heat Stress in Arabidopsis thaliana.

Environmental stress is one of the most important factors affecting plant growth and development. Recent studies have shown that epigenetic mechanisms, such as DNA methylation, play a key role in adapting plants to stress conditions. Here, we analyzed the dynamics of changes in the level of DNA methylation in Arabidopsis thaliana (L.) Heynh. (Brassicaceae) under the influence of heat stress. For this purpose, whole-genome sequencing of sodium bisulfite-treated DNA was performed. The analysis was performed at seven time points, taking into account the control conditions, heat stress, and recovery to control conditions after the stress treatment was discontinued. In our study we observed decrease in the level of DNA methylation under the influence of heat stress, especially after returning to control conditions. Analysis of the gene ontology enrichment and regulatory pathways showed that genes characterized by differential DNA methylation are mainly associated with stress response, including heat stress. These are the genes encoding heat shock proteins and genes associated with translation regulation. A decrease in the level of DNA methylation in such specific sites suggests that under the influence of heat stress we observe active demethylation phenomenon rather than passive demethylation, which is not locus specific.

Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells.

The androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and metastasis. Thus, blocking AR activity and its downstream signaling constitutes a major strategy for PCa treatment. Here, we report on the potent anti-PCa activity of a small-molecule imidazoacridinone, C-1311. In AR-positive PCa cells, C-1311 was found to inhibit the transcriptional activity of AR, uncovering a novel mechanism that may be relevant for its anticancer effect. Mechanistically, C-1311 decreased the AR binding to the prostate-specific antigen (PSA) promoter, reduced the PSA protein level, and, as shown by transcriptome sequencing, downregulated numerous AR target genes. Importantly, AR-negative PCa cells were also sensitive to C-1311, suggesting a promising efficacy in the androgen-independent PCa sub-type. Irrespective of AR status, C-1311 induced DNA damage, arrested cell cycle progression, and induced apoptosis. RNA sequencing indicated significant differences in the transcriptional response to C-1311 between the PCa cells. Gene ontology analysis showed that in AR-dependent PCa cells, C-1311 mainly affected the DNA damage response pathways. In contrast, in AR-independent PCa cells, C-1311 targeted the cellular metabolism and inhibited the genes regulating glycolysis and gluconeogenesis. Together, these results indicate that C-1311 warrants further development for the treatment of PCa.

Clinical and epidemiological characteristics of multiple sclerosis patients receiving disease-modifying treatment in Poland.

AIM OF STUDY: The aim of this study was to collect and analyse data on relapsing-remitting multiple sclerosis (RRMS) patients receiving disease-modifying therapies (DMTs) in Poland. MATERIAL AND METHODS: This observational, multicentre study with prospective data collection included RRMS patients receiving DMTs reimbursed by the National Health Fund (NFZ) in Poland, monitored by the Therapeutic Programme Monitoring System (SMPT). Demographic profiles, disability status, and treatment modalities were analysed. RESULTS: Data from 11,632 RRMS patients was collected (from 15,368 new prescriptions), including 10,649 patients in the first-line and 983 in the second-line therapeutic programme of DMTs. The proportion of females to males was 2.39 in the first-line and 1.91 in the second-line. The mean age at DMTs start was 36.6 years in the first-line and 35.1 in the second-line. The median time from the first symptoms to MS diagnosis was 7.4 months, and from MS diagnosis to treatment it was 18.48 months. A total of 43.4% of MS patients started DMT during the 12 months following diagnosis. There was a positive correlation between the duration from MS diagnosis to the start of DMT and a higher initial EDSS value [correlation 0.296 (p < 0.001)]. About 10% of patients stopped DMTs. In Poland, about one third of all MS patients are treated in both lines, and the choice of first-line treatment depends on the region of the country. CONCLUSIONS: In Poland there is a need to increase MS patient access to DMTs by improving the organisation of drug programmes.

Systematic Review of Polygenic Risk Scores for Type 1 and Type 2 Diabetes.

Recent studies have led to considerable advances in the identification of genetic variants associated with type 1 and type 2 diabetes. An approach for converting genetic data into a predictive measure of disease susceptibility is to add the risk effects of loci into a polygenic risk score. In order to summarize the recent findings, we conducted a systematic review of studies comparing the accuracy of polygenic risk scores developed during the last two decades. We selected 15 risk scores from three databases (Scopus, Web of Science and PubMed) enrolled in this systematic review. We identified three polygenic risk scores that discriminate between type 1 diabetes patients and healthy people, one that discriminate between type 1 and type 2 diabetes, two that discriminate between type 1 and monogenic diabetes and nine polygenic risk scores that discriminate between type 2 diabetes patients and healthy people. Prediction accuracy of polygenic risk scores was assessed by comparing the area under the curve. The actual benefits, potential obstacles and possible solutions for the implementation of polygenic risk scores in clinical practice were also discussed. Develop strategies to establish the clinical validity of polygenic risk scores by creating a framework for the interpretation of findings and their translation into actual evidence, are the way to demonstrate their utility in medical practice.

Response of rhizospheric and endophytic bacterial communities of white mustard (Sinapis alba) to bioaugmentation of soil with the Pseudomonas sp. H15 strain.

A factor that may significantly increase the efficacy of phytoextraction is soil bioaugmentation with specific bacteria, which can alter the composition of rhizospheric and endophytic bacterial communities. The aim of this study was to compare the effect of soil treatment with living (bioaugmentation) and dead (control) cells of the plant growth-promoting metal-resistant endophytic strain Pseudomonas sp. H15 on the bacterial community composition in the rhizo- and endo-sphere of white mustard during enhanced phytoextraction. The bacterial communities in the rhizosphere were dominated (51.7-68.2%) by Proteobacteria, regardless of the soil treatment or sampling point. A temporary increase in the number of sequences belonging to Gammaproteobacteria (up to 37.3%) was only observed 24 h after the soil treatment with living Pseudomonas sp. H15 cells, whereas for the remaining samples, the relative abundance of this class did not exceed 7.1%. The relative abundance of Proteobacteria in the endosphere of the roots, stems, and leaves of white mustard was higher in the control than in bioaugmented plants. The most pronounced dominance of the Gammaproteobacteria sequences was observed in the stems and leaves of the control plants at the first sampling point, which strongly indicates the ability of the plants to rapidly uptake DNA from soil and translocate it to the aboveground parts of the plants. Additionally, the bioaugmentation of the soil caused a diverse shift in the bacterial communities in the rhizo- and endo-sphere of white mustard compared to control. The most distinct differences, which were dependent on the treatment, were observed in the endosphere of plants at the beginning of the experiment and decreased over time. These results indicate that the rhizo- and endo-biome of white mustard reacts to soil bioaugmentation and may influence the efficiency of bacterial-assisted phytoextraction.

Insights into Barley Root Transcriptome under Mild Drought Stress with an Emphasis on Gene Expression Regulatory Mechanisms.

Root systems play a pivotal role in coupling with drought stress, which is accompanied with a substantial transcriptome rebuilding in the root tissues. Here, we present the results of global gene expression profiling of roots of two barley genotypes with contrasting abilities to cope with drought that were subjected to a mild level of the stress. We concentrate our analysis on gene expression regulation processes, which allowed the identification of 88 genes from 39 families involved in transcriptional regulation in roots upon mild drought. They include 13 genes encoding transcription factors (TFs) from AP2 family represented by ERFs, DREB, or B3 domain-containing TFs, eight WRKYs, six NACs, five of the HD-domain, MYB or MYB-related, bHLH and bZIP TFs. Also, the representatives of C3H, CPP, GRAS, LOB-domain, TCP, Tiffy, Tubby, and NF-Ys TFs, among others were found to be regulated by the mild drought in barley roots. We found that drought tolerance is accompanied with a lower number of gene expression changes than the amount observed in a susceptible genotype. The better drought acclimation may be related to the activation of transcription factors involved in the maintenance of primary root growth and in the epigenetic control of chromatin and DNA methylation. In addition, our analysis pointed to fives TFs from ERF, LOB, NAC, WRKY and bHLH families that may be important in the mild but not the severe drought response of barley roots.

Molecular Signature of Subtypes of Non-Small-Cell Lung Cancer by Large-Scale Transcriptional Profiling: Identification of Key Modules and Genes by Weighted Gene Co-Expression Network Analysis (WGCNA).

Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies consisting essentially of adenocarcinoma (ADC) and squamous cell carcinoma (SCC). Although the diagnosis and treatment of ADC and SCC have been greatly improved in recent decades, there is still an urgent need to identify accurate transcriptome profile associated with the histological subtypes of NSCLC. The present study aims to identify the key dysregulated pathways and genes involved in the development of lung ADC and SCC and to relate them with the clinical traits. The transcriptional changes between tumour and normal lung tissues were investigated by RNA-seq. Gene ontology (GO), canonical pathways analysis with the prediction of upstream regulators, and weighted gene co-expression network analysis (WGCNA) to identify co-expressed modules and hub genes were used to explore the biological functions of the identified dysregulated genes. It was indicated that specific gene signatures differed significantly between ADC and SCC related to the distinct pathways. Of identified modules, four and two modules were the most related to clinical features in ADC and SCC, respectively. CTLA4, MZB1, NIP7, and BUB1B in ADC, as well as GNG11 and CCNB2 in SCC, are novel top hub genes in modules associated with tumour size, SUVmax, and recurrence-free survival. Our research provides a more effective understanding of the importance of biological pathways and the relationships between major genes in NSCLC in the perspective of searching for new molecular targets.

The effectiveness of interferon beta versus glatiramer acetate and natalizumab versus fingolimod in a Polish real-world population.

OBJECTIVE: The aim of the study was to assess the effectiveness of disease-modifying therapies (DMTs) in relapsing-remitting multiple sclerosis (RRMS) patients treated in MS centres in Poland. METHODS: Demographic and clinical data of all Polish RRMS patients receiving DMTs were prospectively collected from 2014 to 2018 in electronic files using the Therapeutic Program Monitoring System (SMPT). RESULTS: The study included 10,764 RRMS patients treated with DMTs in first-line and 1,042 in second-line programmes. IFNß more effectively lengthened the times to the first relapse, disability progression, and brain MRI activity than GA. After 2 and 4 years of follow-up, more patients on IFNß showed no evidence of disease activity (NEDA-3) in comparison to GA (66.3% and 44.3% vs 55.2% and 33.2%, respectively; p<0.001). NAT more effectively reduced brain MRI activity than FTY (p = 0.001). More patients under NAT had NEDA-3 after 2 and 4 years of follow-up compared to FTY (66.2% and 42.1% vs 52.1% and 29.5%, respectively; p = 0.03). In adjusted analysis, a higher baseline Expanded Disability Status Score (EDSS) was a predictor of relapse (p<0.001) and NEDA-3 failure (p = 0.003). CONCLUSION: IFNß compared to GA and NAT compared to FTY more effectively reduced disease activity in a Polish population of RRMS patients.

DNA Methylation Analysis in Barley and Other Species with Large Genomes.

Detailed DNA methylation analyses in plant species with large and highly repetitive genomes can be challenging as well as costly. Here, we describe a complete protocol for a high-throughput DNA methylation changes analysis using Methylation-Sensitive Amplification Polymorphism Sequencing (MSAP-Seq; Chwialkowska et al., Front Plant Sci. 8: 2056 (2017)). This method allows detailed information about DNA methylation changes in large and complex genomes to be obtained at a relatively low cost. MSAP-Seq is based on conventional MSAP marker analysis and employs all its basic steps such as restriction cleavage with methylation-sensitive restriction enzyme, ligation of universal adapters, and PCR amplification. However, the traditional gel-based amplicon separation is replaced by direct, global sequencing with next-generation sequencing (NGS) methods. Consequently, MSAP-Seq allows for parallel analysis of hundreds of thousands of different CCGG sites and evaluation of their DNA methylation state. This technique especially targets to genic regions, so it is well suited for large genomes with low gene density, such as barley and other plants with large genomes.

Forward Genetics Approach Reveals a Mutation in bHLH Transcription Factor-Encoding Gene as the Best Candidate for the Root Hairless Phenotype in Barley.

Root hairs are the part of root architecture contributing significantly to the root surface area. Their role is particularly substantial in maintaining plant growth under stress conditions, however, knowledge on mechanism of root hair differentiation is still limited for majority of crop species, including barley. Here, we report the results of a map-based identification of a candidate gene responsible for the lack of root epidermal cell differentiation, which results in the lack of root hairs in barley. The analysis was based on the root hairless barley mutant rhl1.b, obtained after chemical mutagenesis of spring cultivar 'Karat'. The rhl1 gene was located in chromosome 7HS in our previous studies. Fine mapping allowed to narrow the interval encompassing rhl1 gene to 3.7 cM, which on physical barley map spans a region of 577 kb. Five high confidence genes are located within this region and their sequencing resulted in the identification of A>T mutation in one candidate, HORVU7Hr1G030250 (MLOC_38567), differing the mutant from its parent variety. The mutation, located in the 3' splice-junction site, caused the retention of the last intron, 98 bp long, in mRNA of rhl1.b allele. This resulted in the frameshift, the synthesis of 71 abnormal amino acids and introduction of premature STOP codon in mRNA. The mutation was present in the recombinants from the mapping population (F2rhl1.b × 'Morex') that lacked root hairs. The candidate gene encodes a bHLH transcription factor with LRL domain and may be involved in early stages of root hair cell development. We discuss the possible involvement of HORVU7Hr1G030250 in this process, as the best candidate responsible for early stages of rhizodermis differentiation in barley.

Evaluation of Genome-Wide Markers and Orthologous Markers in Brachypodium distachyon.

Molecular markers play an important role in identifying the species variation, characterizing the genic diversity, and also linking the identified markers to trait of interest. Genome- and transcriptome-derived molecular markers have been widely used to understand the geographical diversity and have also played a major role in the development of high-density linkage maps. In the present protocol, we present a detailed protocol on bioinformatics approaches towards the whole-genome and transcriptome-assisted simple sequence repeats (SSRs) marker mining in Brachypodium distachyon and identification of orthologus SSRs and their validation in Brachypodium ecotypes. We also present a protocol for the validation of the identified markers.

Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq)-A Method for High-Throughput Analysis of Differentially Methylated CCGG Sites in Plants with Large Genomes.

Epigenetic mechanisms, including histone modifications and DNA methylation, mutually regulate chromatin structure, maintain genome integrity, and affect gene expression and transposon mobility. Variations in DNA methylation within plant populations, as well as methylation in response to internal and external factors, are of increasing interest, especially in the crop research field. Methylation Sensitive Amplification Polymorphism (MSAP) is one of the most commonly used methods for assessing DNA methylation changes in plants. This method involves gel-based visualization of PCR fragments from selectively amplified DNA that are cleaved using methylation-sensitive restriction enzymes. In this study, we developed and validated a new method based on the conventional MSAP approach called Methylation Sensitive Amplification Polymorphism Sequencing (MSAP-Seq). We improved the MSAP-based approach by replacing the conventional separation of amplicons on polyacrylamide gels with direct, high-throughput sequencing using Next Generation Sequencing (NGS) and automated data analysis. MSAP-Seq allows for global sequence-based identification of changes in DNA methylation. This technique was validated in Hordeum vulgare. However, MSAP-Seq can be straightforwardly implemented in different plant species, including crops with large, complex and highly repetitive genomes. The incorporation of high-throughput sequencing into MSAP-Seq enables parallel and direct analysis of DNA methylation in hundreds of thousands of sites across the genome. MSAP-Seq provides direct genomic localization of changes and enables quantitative evaluation. We have shown that the MSAP-Seq method specifically targets gene-containing regions and that a single analysis can cover three-quarters of all genes in large genomes. Moreover, MSAP-Seq's simplicity, cost effectiveness, and high-multiplexing capability make this method highly affordable. Therefore, MSAP-Seq can be used for DNA methylation analysis in crop plants with large and complex genomes.

Systematic biobanking, novel imaging techniques, and advanced molecular analysis for precise tumor diagnosis and therapy: The Polish MOBIT project.

Personalized and precision medicine is gaining recognition due to the limitations by standard diagnosis and treatment; many areas of medicine, from cancer to psychiatry, are moving towards tailored and individualized treatment for patients based on their clinical characteristics and genetic signatures as well as novel imaging techniques. Advances in whole genome sequencing have led to identification of genes involved in a variety of diseases. Moreover, biomarkers indicating severity of disease or susceptibility to treatment are increasingly being characterized. The continued identification of new genes and biomarkers specific to disease subtypes and individual patients is essential and inevitable for translation into personalized medicine, in estimating both, disease risk and response to therapy. Taking into consideration the mostly unsolved necessity of tailored therapy in oncology the innovative project MOBIT (molecular biomarkers for individualized therapy) was designed. The aims of the project are: (i) establishing integrative management of precise tumor diagnosis and therapy including systematic biobanking, novel imaging techniques, and advanced molecular analysis by collecting comprehensive tumor tissues, liquid biopsies (whole blood, serum, plasma), and urine specimens (supernatant; sediment) as well as (ii) developing personalized lung cancer diagnostics based on tumor heterogeneity and integrated genomics, transcriptomics, metabolomics, and radiomics PET/MRI analysis. It will consist of 5 work packages. In this paper the rationale of the Polish MOBIT project as well as its design is presented. (iii) The project is to draw interest in and to invite national and international, private and public, preclinical and clinical initiatives to establish individualized and precise procedures for integrating novel targeted therapies and advanced imaging techniques.

No Time to Waste: Transcriptome Study Reveals that Drought Tolerance in Barley May Be Attributed to Stressed-Like Expression Patterns that Exist before the Occurrence of Stress.

Plant survival in adverse environmental conditions requires a substantial change in the metabolism, which is reflected by the extensive transcriptome rebuilding upon the occurrence of the stress. Therefore, transcriptomic studies offer an insight into the mechanisms of plant stress responses. Here, we present the results of global gene expression profiling of roots and leaves of two barley genotypes with contrasting ability to cope with drought stress. Our analysis suggests that drought tolerance results from a certain level of transcription of stress-influenced genes that is present even before the onset of drought. Genes that predispose the plant to better drought survival play a role in the regulatory network of gene expression, including several transcription factors, translation regulators and structural components of ribosomes. An important group of genes is involved in signaling mechanisms, with significant contribution of hormone signaling pathways and an interplay between ABA, auxin, ethylene and brassinosteroid homeostasis. Signal transduction in a drought tolerant genotype may be more efficient through the expression of genes required for environmental sensing that are active already during normal water availability and are related to actin filaments and LIM domain proteins, which may function as osmotic biosensors. Better survival of drought may also be attributed to more effective processes of energy generation and more efficient chloroplasts biogenesis. Interestingly, our data suggest that several genes involved in a photosynthesis process are required for the establishment of effective drought response not only in leaves, but also in roots of barley. Thus, we propose a hypothesis that root plastids may turn into the anti-oxidative centers protecting root macromolecules from oxidative damage during drought stress. Specific genes and their potential role in building up a drought-tolerant barley phenotype is extensively discussed with special emphasis on processes that take place in barley roots. When possible, the interconnections between particular factors are emphasized to draw a broader picture of the molecular mechanisms of drought tolerance in barley.