Tracking the functional meaning of the human oral-microbiome protein-protein interactions.

The interactome - the network of protein-protein interactions (PPIs) within a cell or organism - is technically difficult to assess. Bioinformatic tools can, not only, identify potential PPIs that can be later experimentally validated, but also be used to assign functional meaning to PPIs. Saliva's potential as a non-invasive diagnostic fluid is currently being explored by several research groups. But, in order to fully attain its potential, it is necessary to achieve the full characterization of the mechanisms that take place within this ecosystem. The onset of omics technologies, and specifically of proteomics, delivered a huge set of data that is largely underexplored. Quantitative information relative to proteins within a given context (for example a given disease) can be used by computational algorithms to generate information regarding PPIs. These PPIs can be further analyzed concerning their functional meaning and used to identify potential biomarkers, therapeutic targets, defense and pathogenicity mechanisms. We describe a computational pipeline that can be used to identify and analyze PPIs between human and microbial proteins. The pipeline was tested within the scenario of human PPIs of systemic (Zika Virus infection) and of oral conditions (Periodontal disease) and also in the context of microbial interactions (Candida-Streptococcus) and showed to successfully predict functionally relevant PPIs. The pipeline can be applied to different scientific areas, such as pharmacological research, since a functional meaningful PPI network can provide insights on potential drug targets, and even new uses for existing drugs on the market.

Obstructive Acute Kidney Injury with Maintenance of Diuresis: A Case of Ureter Bifidity / Lesión Renal Aguda Obstructiva con Mantenimiento de la Diuresis: Un Caso de BifidezUreteral

Abstract Percutaneous kidney biopsyin transplanted kidneys remains an essential and commonly performed procedure required for diagnostic and prognostic information. Hemorrhage is the main complication of renal graft biopsy. We report a case of a 47-year-old caucasian womanadmitted to perform an ultrasound(US)-guided biopsy of the renal graft. Six hours later, she presented with macroscopic hematuriawhichimproved after urethral catheterization and intravenous hydration. However the hematuria reappeared associated with anemia and worsening of the serum creatinine value. The US study, revealed hydronephrosis with high Doppler derived renal resistive index compatible with clot obstruction.Despite the vesical lavage with drainage of several clots, the patient rapidly progressed to hemorrhagic shock with worsening of renal function. Pelvic computed tomography (CT) revealed calyx and pelvis duplicity and ureter bifidity which merged into a single ureter and inserted into the right anterolateral wall of the bladder. The inferior ureter was enlarged due to an obstructive clot. Most acute obstructive uropathies are associated with significant pain or the abrupt diminution of urine flow. The presence of ureter bifidity in the CT study explained the maintenance of significantdiuresis despite obstruction, located only to the lower ureter but with sufficient functional impact to condition acute kidney injury (AKI).

Resumen La biopsia renal percutánea en riñones trasplantados sigue siendo un procedimiento esencial y común, necesario para obtener información diagnóstica y pronóstica. La hemorragia es la principal complicación de la biopsia de injerto renal. Presentamos un caso de una mujer caucásica de 47 años, quien fue hospitalizada para la realización de una biopsia de injerto renal guiada por ultrasonido (US). Seis horas después, presentó hematuria macroscópica que mejoró después de la cateterización uretral e hidratación intravenosa. Sin embargo, la hematuria reapareció asociada con anemia y empeoramiento del valor sérico de creatinina. El estudio de US reveló, mediante Doppler, una hidronefrosis con alto índice de resistencia renal, compatible con obstrucción por un coágulo. A pesar del lavado vesical con drenaje de varios coágulos, la paciente progresó rápidamente a choque hemorrágico con empeoramiento de la función renal. La tomografía computarizada (TC) pélvica reveló la duplicidad del cáliz y la pelvis y la bifidez ureteral, que se fusionó en un solo uréter y se insertó en la pared anterolateral derecha de la vejiga. El uréter inferior se agrandó debido a un coágulo obstructivo. La mayoría de las uropatías obstructivas agudas están asociadas con dolor significativo o la disminución abrupta del flujo de orina. La presencia de la bifidez del uréter en el estudio de TC explicó el mantenimiento de una diuresis significativa a pesar de la obstrucción, localizada solo en el uréter inferior, pero con suficiente impacto funcional como para provocar insuficiencia renal aguda (IRA).

CanisOme--The protein signatures of Canis lupus familiaris diseases.

Although the applications of Proteomics in Human Biomedicine have been explored for some time now, in animal and veterinary research, the potential of this resource has just started to be explored, especially when companion animal health is considered. In the last years, knowledge on the Canis lupus familiaris proteome has been accumulating in the literature and a resource compiling all this information and critically reviewing it was lacking. This article presents such a resource for the first time. CanisOme is a database of all proteins identified in Canis lupus familiaris tissues, either in health or in disease, annotated with information on the proteins present on the sample and on the donors. This database reunites information on 549 proteins, associated with 63 dog diseases and 33 dog breeds. Examples of how this information may be used to produce new hypothesis on disease mechanisms is presented both through the functional analysis of the proteins quantified in canine cutaneous mast cell tumors and through the study of the interactome of C. lupus familiaris and Leishmania infantum. Therefore, the usefulness of CanisOme for researchers looking for protein biomarkers in dogs and interested in a comprehensive analysis of disease mechanisms is demonstrated. BIOLOGICAL SIGNIFICANCE: This paper presents CanisOme, a database of proteomic studies with relevant protein annotation, allowing the enlightenment of disease mechanisms and the discovery of novel disease biomarkers for C. lupus familiaris. This knowledge is important not only for the improvement of animal health but also for the use of dogs as models for human health studies.

The landscape of protein biomarkers proposed for periodontal disease: markers with functional meaning.

Periodontal disease (PD) is characterized by a deregulated inflammatory response which fails to resolve, activating bone resorption. The identification of the proteomes associated with PD has fuelled biomarker proposals; nevertheless, many questions remain. Biomarker selection should favour molecules representing an event which occurs throughout the disease progress. The analysis of proteome results and the information available for each protein, including its functional role, was accomplished using the OralOme database. The integrated analysis of this information ascertains if the suggested proteins reflect the cell and/or molecular mechanisms underlying the different forms of periodontal disease. The evaluation of the proteins present/absent or with very different concentrations in the proteome of each disease state was used for the identification of the mechanisms shared by different PD variants or specific to such state. The information presented is relevant for the adequate design of biomarker panels for PD. Furthermore, it will open new perspectives and help envisage future studies targeted to unveil the functional role of specific proteins and help clarify the deregulation process in the PD inflammatory response.