2D proteome analysis initiates new Insights on the Salmonella Typhimurium LuxS protein

Background  

Quorum sensing is a term describing a bacterial communication system mediated by the production and recognition of small signaling molecules. The LuxS enzyme, catalyzing the synthesis of AI-2, is conserved in a wide diversity of bacteria. AI-2 has therefore been suggested as an interspecies quorum sensing signal. To investigate the role of endogenous AI-2 in protein expression of the Gram-negative pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), we performed a 2D-DIGE proteomics experiment comparing total protein extract of wildtype S. Typhimurium with that of a luxS mutant, unable to produce AI-2.     

Developing a scalable model of recombinant protein yield from Pichia pastoris: the influence of culture conditions, biomass and induction regime

Background  

The optimisation and scale-up of process conditions leading to high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences. Typical experiments rely on varying selected parameters through repeated rounds of trial-and-error optimisation. To rationalise this, several groups have recently adopted the 'design of experiments' (DoE) approach frequently used in industry. Studies have focused on parameters such as medium composition, nutrient feed rates and induction of expression in shake flasks or bioreactors, as well as oxygen transfer rates in micro-well plates. In this study we wanted to generate a predictive model that described small-scale screens and to test its scalability to bioreactors.     

Quality of life improvement in patients with bone metastases undergoing palliative radiotherapy

BackgroundThe aim of the study was to analyze the impact of palliative radiotherapy on quality of life (QoL) in patients with symptomatic bone metastases.Materials and methodsWe present the results from a prospective multicentric study including 128 patients who provided pre- and post-radiotherapy (one month after treatment) brief pain inventory (BPI) assessments. Worst pain was recorded using the BPI (range: 0–10). Pain response was described according to the International Bone Metastases Consensus on palliative radiation. Regarding QoL, for each pre- and post-radiation BPI-questionnaire, scores from the interference domains were summed and averaged to obtain an overall interference score.ResultsThere was a significant correlation between radiation treatment response and improvement in all functional interference domains except sleeping. Patients > 75 years old presented a significantly higher improvement in general activity, mood and relationships with others compared to patients ≤ 75 years old. Patients presenting a baseline pain score ≥ 8 showed a higher improvement in the general activity item (p = 0.049). There was no statistically significant association between pretreatment ECOG, chemotherapy, primary tumor location and radiation schedule with any of the functional interference items.ConclusionsPatients who report pain relief after palliative radiotherapy also present a better quality of life including physical and psychosocial aspects.     

A consensus view of the proteome of the last universal common ancestor

The availability of genomic and proteomic data from across the tree of life has made it possible to infer features of the genome and proteome of the last universal common ancestor (LUCA). A number of studies have done so, all using a unique set of methods and bioinformatics databases. Here, we compare predictions across eight such studies and measure both their agreement with one another and with the consensus predictions among them. We find that some LUCA genome studies show a strong agreement with the consensus predictions of the others, but that no individual study shares a high or even moderate degree of similarity with any other individual study. From these observations, we conclude that the consensus among studies provides a more accurate depiction of the core proteome of the LUCA and its functional repertoire. The set of consensus LUCA protein family predictions between all of these studies portrays a LUCA genome that, at minimum, encoded functions related to protein synthesis, amino acid metabolism, nucleotide metabolism, and the use of common, nucleotide‐derived organic cofactors.     

COVID-19 y salas de análisis del riesgo en salud pública en cuatro departamentos fronterizos de Colombia

Introduction:

Public health risk management in Colombia is led by the Instituto Nacional de Salud. In the face of the COVID-19 emergency, response actions centered on the implementation of risk analysis rooms and the strengthening of surveillance at points of entry into the country.

Objective:

To analyze the implementation and maintenance phases of the COVID-19 risk analysis rooms in four border departments of Colombia.

Materials and methods:

We conducted a qualitative study of public health risk analysis rooms for COVID-19. We reviewed the documentation and data generated from March to June, 2020, in the departments of Amazonas, Vichada, Guainía, and Putumayo. We did semi-structured interviews with key actors and analyzed the answers using the NVivo plus version 11 application in three cycles: open coding, identification of emerging categories, and modeling by analyzing the identified strengths and weaknesses.

Results:

We identified the components of the incident command structure and the relationships between the public health areas. Strengths were evidenced in the integration of the areas: the management of information in real time, the border surveillance and the capabilities of rapid response teams, while weaknesses appeared in planning, community surveillance, and risk communication processes.

Conclusions:

Risk analysis rooms constitute a joint effort at the national and local levels which has promoted the articulated participation of all actors in the analysis of information and the optimization of an organized response during the COVID-19 pandemic.     

The role of the C(2) configuration and methyl substitution on the catalytic activity of novel 2,3,3‐ and 2,7,7‐trimethyl‐substituted γ‐aminonorbornan‐2‐ols

A new set of optically active 2,3,3‐ and 2,7,7‐trimethyl‐substituted γ‐aminonorbornan‐2‐ols have been obtained from 2‐methylenenorbornane‐1‐carbonitriles derived from (+)‐camphor and (?)‐fenchone and probed as chiral ligands for the enantioselective addition of diethylzinc to benzaldehyde. This has allowed the study of the structural factors influencing the chirality transfer, such as variation of the relative configuration at C(2) and steric hindrance at C(2), C(3), and C(7) positions of norbornane, which result in the observance of the important role played by the gem‐dimethyl position in γ‐aminonorbornan‐2‐exo‐ols. An empirical rationalization of the obtained experimental results has been realized on the basis of energetically‐favored diastereomeric Noyori‐like transition states. Chirality 2010. © 2010 Wiley‐Liss, Inc.     

Mitochondrial dysfunction promoted by Porphyromonas gingivalis lipopolysaccharide as a possible link between cardiovascular disease and periodontitis

Oxidative stress is one of the factors that could explain the pathophysiological mechanism of inflammatory conditions that occur in cardiovascular disease (CVD) and periodontitis. Such inflammatory response is often evoked by specific bacteria, as the lipopolysaccharide (LPS) of Porphyromonas gingivalis is a key factor in this process. The aim of this research was to study the role of mitochondrial dysfunction in peripheral blood mononuclear cells (PBMCs) from periodontitis patients and to evaluate the influence of LPS on fibroblasts to better understand the pathophysiology of periodontitis and its relationship with CVD. PBMCs from patients showed lower CoQ10 levels and citrate synthase activity, together with high levels of ROS production. LPS-treated fibroblasts provoked increased oxidative stress and mitochondrial dysfunction by a decrease in mitochondrial protein expression, mitochondrial mass, and mitochondrial membrane potential. Our study supports the hypothesis that LPS-mediated mitochondrial dysfunction could be at the origin of oxidative stress in periodontal patients. Abnormal PBMC performance may promote oxidative stress and alter cytokine homeostasis. In conclusion, mitochondrial dysfunction could represent a possible link to understanding the interrelationships between two prominent inflammatory diseases: periodontitis and CVD.     

Application Of The American College Of Emergency Physicians (ACEP) Recommendations And a Risk Stratification Score (OESIL) For Patients With Syncope Admitted From The Emergency Department

Aims

The goals of this study were to apply the 2001 ACEP recommendations for admission to hospital after a syncopal event and to validate the OESIL risk stratification score, in patients with syncope admitted to a general internal medicine ward.

Methods

A retrospective study applied the 2001 ACEP recommendations and OESIL score to all the patients admitted from the emergency department to a general internal medicine ward with a diagnosis of syncope during a 12-month period. The patients were classified as meeting criteria for 2001 ACEP class B or C recommendations and OESIL score 0-1 (low-risk for a major cardiac event) or 2-4 (high-risk for a major cardiac event). The sensitivity and specificity of each group for predicting high-risk patients was calculated.

Results

After applying the 2001 ACEP recommendations to our population, 25% (19 patients) were classified as level B, whereas 68% of the patients were classified as Level C. Sensitivity for ACEP level B recommendations was 100% and specificity was 81%. The ACEP level C recommendations also had 100% sensitivity but markedly reduced specificity at 26%. An OESIL score of 0-1 points was calculated for 30.6% of the population, identifying them as low-risk. An OESIL score of 2-4 points was documented in the remaining 69.4% with a mortality risk of 20 % /year.

Conclusion

A significant proportion (30%) of patients presenting with syncope to a tertiary care University Hospital emergency department and admitted to an Internal Medicine ward were retrospectively classified as low-risk and could have potentially been managed as outpatients. Implementing current guidelines and clinical pathways for the management of syncope may improve this approach.     

Soluble IL-18 receptor complex: a new star in the firmament of rheumatoid arthritis diagnosis?

It has long been recognized that laboratory tests are useful in the diagnosis of disease and to monitor treatment outcome. Their performance has become even more demanding with the development of personalized medicine. In patients with rheumatoid arthritis (RA) the standard biochemical tests measure serological markers of disease, such as C-reactive protein, and RA-associated auto-antibodies, such as rheumatoid factor and anti-citrullinated protein antibodies. The information obtained from these markers does not, however, provide a complete picture of the disease and treatment efficacy. New biomarkers based on cytokine receptor complexes are promising for RA theragnostics.     

Human Blue Cone Opsin Regeneration Involves Secondary Retinal Binding with Analog Specificity

Human color vision is mediated by the red, green, and blue cone visual pigments. Cone opsins are G-protein-coupled receptors consisting of an opsin apoprotein covalently linked to the 11-cis-retinal chromophore. All visual pigments share a common evolutionary origin, and red and green cone opsins exhibit a higher homology, whereas blue cone opsin shows more resemblance to the dim light receptor rhodopsin. Here we show that chromophore regeneration in photoactivated blue cone opsin exhibits intermediate transient conformations and a secondary retinoid binding event with slower binding kinetics. We also detected a fine-tuning of the conformational change in the photoactivated blue cone opsin binding site that alters the retinal isomer binding specificity. Furthermore, the molecular models of active and inactive blue cone opsins show specific molecular interactions in the retinal binding site that are not present in other opsins. These findings highlight the differential conformational versatility of human cone opsin pigments in the chromophore regeneration process, particularly compared to rhodopsin, and point to relevant functional, unexpected roles other than spectral tuning for the cone visual pigments.