Charting the evolutionary path of the SUMO modification system in plants reveals molecular hardwiring of development to stress adaptation.

SUMO modification is part of the spectrum of Ubiquitin-like (UBL) systems that give rise to proteoform complexity through post-translational modifications (PTMs). Proteoforms are essential modifiers of cell signaling for plant adaptation to changing environments. Exploration of the evolutionary emergence of Ubiquitin-like (UBL) systems unveils their origin from prokaryotes where it is linked to the mechanisms that enable sulfur uptake into biomolecules. We explore the emergence of the SUMO machinery across the plant lineage from single-cell to land plants. We reveal the evolutionary point at which plants acquired the ability to form SUMO chains through the emergence of SUMO E4 ligases hinting at its role in facilitating multicellularity. Additionally, we explore the possible mechanism for the neofunctionalization of SUMO proteases through the fusion of conserved catalytic domains with divergent sequences. We highlight the pivotal role of SUMO proteases in plant development and adaptation, offering new insights into target specificity mechanisms of SUMO modification during plant evolution. Correlating the emergence of adaptive traits in the plant lineage with established experimental evidence for SUMO in developmental processes we propose that SUMO modification has evolved to link developmental processes to adaptive functions in land plants.

Discovering potential interactions between rare diseases and COVID-19 by combining mechanistic models of viral infection with statistical modeling.

Recent studies have demonstrated a relevant role of the host genetics in the coronavirus disease 2019 (COVID-19) prognosis. Most of the 7000 rare diseases described to date have a genetic component, typically highly penetrant. However, this vast spectrum of genetic variability remains yet unexplored with respect to possible interactions with COVID-19. Here, a mathematical mechanistic model of the COVID-19 molecular disease mechanism has been used to detect potential interactions between rare disease genes and the COVID-19 infection process and downstream consequences. Out of the 2518 disease genes analyzed, causative of 3854 rare diseases, a total of 254 genes have a direct effect on the COVID-19 molecular disease mechanism and 207 have an indirect effect revealed by a significant strong correlation. This remarkable potential of interaction occurs for >300 rare diseases. Mechanistic modeling of COVID-19 disease map has allowed a holistic systematic analysis of the potential interactions between the loss of function in known rare disease genes and the pathological consequences of COVID-19 infection. The results identify links between disease genes and COVID-19 hallmarks and demonstrate the usefulness of the proposed approach for future preventive measures in some rare diseases.

Lymphoplasmacytic lymphoma associated with diffuse large B-cell lymphoma: Progression or divergent evolution?

AIM: Lymphoplasmacytic lymphoma (LPL) is an indolent mature B-cell-neoplasm with involvement of the bone marrow. At least 90% of LPLs carry MYD88-L265P mutation and some of them (~10%) transform into diffuse large B-cell-lymphoma (DLBCL). MATERIAL AND METHODS: Over the past 15 years we have collected 7 cases where the both LPL and DLBCL were diagnosed in the same patient. Clinical records, analytical data and histopathological specimens were reviewed. FISH studies on paraffin-embedded tissue for MYC, BCL2 and BCL6 genes were performed, as well as MYD88-L265P mutation and IGH rearrangement analysis by PCR. A mutational study was done by massive next generation sequencing (NGS). RESULTS: There were 4 women and 3 men between 36-91 years of age. Diagnoses were made simultaneously in 4 patients. In two cases the LPL appeared before the DLBCL and in the remaining case the high-grade component was discovered 5 years before the LPL. In 6 cases both samples shared the MYD88-L265P mutation. IGH rearrangement analysis showed overlapping features in two of 6 cases tested. Mutational study was evaluable in three cases for both samples showing shared and divergent mutations. CONCLUSIONS: These data suggest different mechanisms of DLBCL development in LPL patients.

Staphylococcus aureus Prosthetic Joint Infection Is Prevented by a Fluorine- and Phosphorus-Doped Nanostructured Ti-6Al-4V Alloy Loaded With Gentamicin and Vancomycin.

Prosthetic joint infection (PJI) is one of the most devastating complications in orthopedic surgery. One approach used to prevent PJI is local antibiotic therapy. This study evaluates the antibiotic release, in vitro cytocompatibility and in vivo effectiveness in preventing PJI caused by Staphylococcus aureus (S. aureus) of the fluorine- and phosphorus-doped, bottle-shaped, nanostructured (bNT) Ti-6Al-4V alloy loaded with a mixture of gentamicin and vancomycin (GV). We evaluated bNT Ti-6Al-4V loading with a mixture of GV, measuring the release of these antibiotics using high-performance liquid chromatography. Further, we describe bNT Ti-6Al-4V GV cytocompatibility and its efficacy against S. aureus using an in vivo rabbit model. GV was released from bNT Ti-6Al-4V following a Boltzmann non-linear model and maximum release values were obtained at 240 min for both antibiotics. The cell proliferation of MCT3T3-E1 osteoblastic cells significantly increased at 48 (28%) and 168 h (68%), as did the matrix mineralization (52%) of these cells and the gene expression of three of the most important markers related to bone differentiation (more than threefold for VEGF and BGLAP, and 65% for RunX) on bNT Ti-6Al-4V GV compared with control. In vivo study results show that bNT Ti-6Al-4V GV can prevent S. aureus PJI according to histopathological and microbiological results. According to our results, bNT Ti-6Al-4V loaded with a mixture of GV using the soaking method is a promising biomaterial with favorable cytocompatibility and osteointegration, demonstrating local bactericidal properties against S. aureus. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:588-597, 2020.

Urine Aluminum Concentration as a Possible Implant Biomarker of Pseudomonas aeruginosa Infection Using a Fluorine- and Phosphorus-Doped Ti-6Al-4V Alloy with Osseointegration Capacity.

Joint prosthesis failure is mainly related to aseptic loosening and prosthetic joint infections, both associated with high morbidity and a substantial cost burden for patients and health systems. The development of a biomaterial capable of stimulating bone growth while minimizing bacterial adhesion would reduce the incidence of prosthetic failure. Using an in vivo rabbit model, this study evaluates the osseointegration effect of the fluorine (F)- and phosphorus (P)-doped bottle-shaped nanostructured (bNT) Ti-6Al-4V alloy and effectiveness of monitoring urine aluminum concentration to determine the presence of Pseudomonas aeruginosa infection in Ti-6Al-4V implants. Unlike chemically polished (CP) Ti-6Al-4V alloy implants, bNT Ti-6Al-4V alloy implants promoted osseointegration and showed effectiveness as a biomaterial marker. The bNT Ti-6Al-4V alloy implants were associated with a twofold increase in bone thickness and up to 15% greater bone density compared to the CP alloy. Additionally, bNT Ti-6Al-4V alloy implants allowed for discrimination between P. aeruginosa-infected and noninfected animals for 15 days postoperatively, as indicated by the decrease of aluminum concentration in urine, while this difference was only appreciable over the first 7 days when CP Ti-6Al-4V alloy implants were used. Therefore, bNT Ti-6Al-4V alloys could have clinical applications by detecting the infection and by avoiding aseptic loosening.

Proteogenomics in the context of the Human Proteome Project (HPP).

INTRODUCTION: The technological and scientific progress performed in the Human Proteome Project (HPP) has provided to the scientific community a new set of experimental and bioinformatic methods in the challenging field of shotgun and SRM/MRM-based Proteomics. The requirements for a protein to be considered experimentally validated are now well-established, and the information about the human proteome is available in the neXtProt database, while targeted proteomic assays are stored in SRMAtlas. However, the study of the missing proteins continues being an outstanding issue. Areas covered: This review is focused on the implementation of proteogenomic methods designed to improve the detection and validation of the missing proteins. The evolution of the methodological strategies based on the combination of different omic technologies and the use of huge publicly available datasets is shown taking the Chromosome 16 Consortium as reference. Expert commentary: Proteogenomics and other strategies of data analysis implemented within the C-HPP initiative could be used as guidance to complete in a near future the catalog of the human proteins. Besides, in the next years, we will probably witness their use in the B/D-HPP initiative to go a step forward on the implications of the proteins in the human biology and disease.

Inflammasomes in Clinical Practice: A Brief Introduction.

Inflammasomes are multiprotein complexes formed and activated after exposure to pathogenic microbes and host danger signals that control the maturation and production of IL-1ß and IL-18. Their implication in different diseases such as cardiovascular, neurodegenerative, psychiatric, and metabolic diseases opens a door to developing new therapeutic perspectives. However, the rapid increase in the knowledge about inflammasomes is associated with their involvement in clinical practice. Two topics open the way to future lines of research: a clinical trial with the new specific inhibitors and the development of diagnostic tools.

Olive fruit growth and ripening as seen by vibrational spectroscopy.

The aim of this work was to examine the potential of ATR-FTIR and Raman spectroscopies to evaluate changes happening during the development and maturation of olive fruit. To do this, the spectra of the different parts of the olive (skin, flesh and stone) have been measured at different stages of development. The evolution of different spectral bands has been related to the content of olive constituents like triglycerides, water, carotenoids and phenolic compounds. Oil accumulation can be followed using both FTIR and Raman spectroscopy. The increase in bands at 1746 cm(-1) (ATR-FTIR) and 1440 cm(-1) (Raman) correlates well with the oil content in the fruit determined using the standard Soxhlet extraction method. In the case of overripe olives ATR-FTIR does not provide a representative spectrum of the olive flesh due to the accumulation of water on the surface of the ATR crystal. The increase of the content in carotenoids and phenolic compounds during olive growing and their decrease during the ripening phase can be successfully monitored by means of the Raman bands at 1525 and 1605 cm(-1), respectively.

Pharmaceutical powders analysis using FT-Raman spectrometry: simultaneous determination of sulfathiazole and sulfanilamide.

A procedure for rapid quantitative analysis of pharmaceutical powders is described. Powdered samples were measured in a rotating cell in order to avoid sub-sampling problems by increasing the irradiated area. Quantitative determination of sulfathiazole and sulfanilamide, using a simple univariate calibration model is proposed. Even though both antibacterials are of the same chemical family (sulfonamides), the richness of structural information contained in the Raman spectra allowed their determination using the area of two selected bands (1255 and 1629 cm(-1) for sulfathiazole and sulfanilamide, respectively). Relative standard deviation (R.S.D.) values (n=10) of 3.35% and 3.46% for sulfathiazole and sulfanilamide, respectively, demonstrate the good reproducibility of the measurement technique with the rotating cell. The method was successfully applied to the analysis of synthetic mixtures and commercial pharmaceutical powders. The procedure is suitable to be applied to pharmacopoeial uniformity of content testing of batches.

Flow-through sensor with Fourier transform Raman detection for determination of sulfonamides.

A flow-through sensor system with Fourier transform (FT) Raman spectroscopy as detection technique is described. The molecular and structural information contained in Raman spectra together with the selective retention of the species of interest on the sorbent make the proposed methodology highly selective. The flow-through sensor allowed the direct quantitative determination of sulfathiazole and sulfamethoxazole in the presence of other species that are normally encountered with these analytes. The system used Sephadex QAE A-25 resin as packing material of a flow-through cell on which sulfonamides were temporarily retained. Samples were transported by a carrier solution of NaOH 10(-2) mol l(-1) (pH = 12), and 2 ml of a [NaCl (0.10 mol l(-1))/NaOH (10(-2) mol l(-1))] solution was employed as eluent. Using a sample volume of 1 ml, the analytical signal was linear in the range 0.5-7 g l(-1) and 0.5-10 g l(-1), for sulfathiazole and sulfamethoxazole, respectively. RSDs (%) lower than 4% were obtained for both analytes. The sensor was satisfactorily applied to several commercial pharmaceutical preparations for human and animals in different physical presentations, including capsules, syrup, tablets, powders, injectables and suspensions.