Identification of potential invasive alien species in Spain through horizon scanning.

Invasive alien species have widespread impacts on native biodiversity and ecosystem services. Since the number of introductions worldwide is continuously rising, it is essential to prevent the entry, establishment and spread of new alien species through a systematic examination of future potential threats. Applying a three-step horizon scanning consensus method, we evaluated non-established alien species that could potentially arrive, establish and cause major ecological impact in Spain within the next 10 years. Overall, we identified 47 species with a very high risk (e.g. Oreochromis niloticus, Popillia japonica, Hemidactylus frenatus, Crassula helmsii or Halophila stipulacea), 61 with high risk, 93 with moderate risk, and 732 species with low risk. Many of the species categorized as very high or high risk to Spanish biodiversity are either already present in Europe and neighbouring countries or have a long invasive history elsewhere. This study provides an updated list of potential invasive alien species useful for prioritizing efforts and resources against their introduction. Compared to previous horizon scanning exercises in Spain, the current study screens potential invaders from a wider range of terrestrial, freshwater, and marine organisms, and can serve as a basis for more comprehensive risk analyses to improve management and increase the efficiency of the early warning and rapid response framework for invasive alien species. We also stress the usefulness of measuring agreement and consistency as two different properties of the reliability of expert scores, in order to more easily elaborate consensus ranked lists of potential invasive alien species.

Infecciones osteoarticulares en población pediátrica: clínica y microbiología de los últimos 15 años

Introducción: El diagnóstico y tratamiento oportuno de las infecciones osteoarticulares (IOA) pediátricas son imperativos para evitar complicaciones y secuelas, siendo relevante conocer la microbiología local. Objetivo: Describir las características de las IOA pediátricas tratadas en nuestro centro. Pacientes y Métodos: Estudio observacional descriptivo. Se analizaron pacientes bajo 15 años de edad tratados por IOA. entre los años 2004 y 2020. Se evaluaron características clínicas, de laboratorio, microbiología y tratamiento. Resultados: Se incluyeron 126 pacientes (63,5% hombres), con una mediana de edad de 5,09 años (rango: 0,5-14,6 años); 61,1% artritis séptica (AS), 38,9% osteomielitis (OM). Un 92,9% presentó dolor y 68,3% fiebre. La localización más frecuente en AS fue rodilla (33,7%) y en OM tibia (30,6%) y fémur (30,6%). Se identificó agente en 77 pacientes (61,1%), siendo más frecuentes Staphylococcus aureus (n = 44), Kingella kingae (n = 13) y Streptococcuspyogenes (n = 8). Los cuatro pacientes con reacción de polimerasa en cadena (RPC) universal positiva para K. kingae no fueron detectados por otros métodos. Conclusión: El agente más frecuente sigue siendo S. aureus, observándose un aumento en la resistencia de éste en comparación con series nacionales anteriores, y, por primera vez en nuestro medio, se comunica la detección de K. kingae, específicamente relacionada al uso de técnicas moleculares.

Background: Timely diagnosis and treatment of pediatric osteoarticular infections (OAI) are imperative to avoid complications and sequelae, being relevant to know the local microbiology. Aim: To describe the characteristics of pediatric OAI treated in our center. Methods: Descriptive observational study. Patients under 15 years of age treated for OAI between 2004 and 2020 were analyzed. Clinical, laboratory, microbiology and treatment characteristics were evaluated. Results: 126 patients (63.5% men) were included, median age of 5.09 years (range: 0.5-14.6 years); 61.1% had septic arthritis (AS), 38.9% osteomyelitis (OM). Pain was present in 92.9% and fever in 68.3%. The most frequent location in AS was the knee (33.7%) and in OM the tibia (30.6%) and femur (30.6%). Agents were identified in 77 patients (61.1%), the most frequent being Staphylococcus aureus (n = 44), Kingella kingae (n = 13) and Streptococcus pyogenes (n = 8). The 4 patients with positive universal polymerase chain reaction (PCR) for K. kingae were not detected by other methods. Conclusion: The most frequent agent continues to be S. aureus, with an increase in its resistance, and this is the first report of K. kingae as a cause of OAI in Chile, specifically related to the use of molecular techniques.

Endoscopy-Related Bleeding and Thromboembolic Events in Patients on Direct Oral Anticoagulants or Vitamin K Antagonists.

BACKGROUND & AIMS: Few prospective studies have assessed the safety of direct oral anticoagulants (DOACs) in elective endoscopy. Our primary aim was to compare the risks of endoscopy-related gastrointestinal bleeding and thromboembolic events in patients on DOACs or vitamin K antagonists (VKAs) in this setting. Secondarily, we examined the impact of the timing of anticoagulant resumption on the risk of delayed bleeding in high-risk therapeutic procedures. METHODS: We conducted a multicenter, prospective, observational study from January 2018 to March 2020 of 1602 patients on oral anticoagulants (1004 on VKAs and 598 on DOACs) undergoing 1874 elective endoscopic procedures. Our primary outcomes were 90-day thromboembolic events and 30-day endoscopy-related gastrointestinal bleeding. The inverse probability of treatment weighting propensity score method was used for baseline covariate adjustment. RESULTS: The 2 groups had similar risks of endoscopy-related gastrointestinal bleeding (VKAs vs DOACs, 6.2% vs 6.7%; adjusted odds ratio [OR], 1.05; 95% CI, 0.67-1.65) and thromboembolic events (VKAs vs DOACs, 1.3% vs 1.5%; adjusted OR, 0.90; 95% CI, 0.34-2.38). In high bleeding risk procedures (n = 747), delayed anticoagulant resumption (> 48 hours or 24-48 hours vs < 24 hours) did not reduce the risk of postprocedural bleeding (10.3%, 9%, and 5.8%, respectively; adjusted P = .43). Hot and cold snare polypectomy were the most frequent high-risk interventions (41.8% and 39.8%, respectively). CONCLUSION: In a prospective study of patients on DOACs or VKAs undergoing elective endoscopy, endoscopy-related bleeding and thromboembolic events showed similar risk. Our study suggests that early anticoagulant resumption is safe in most patients, but more data are needed for advanced high-risk therapeutic procedures.

The mitochondrial activity of leukocytes from Artibeus jamaicensis bats remains unaltered after several weeks of flying restriction.

Bats are the only flying mammals known. They have longer lifespan than other mammals of similar size and weight and can resist high loads of many pathogens, mostly viruses, with no signs of disease. These distinctive characteristics have been attributed to their metabolic rate that is thought to be the result of their flying lifestyle. Compared with non-flying mammals, bats have lower production of reactive oxygen species (ROS), and high levels of antioxidant enzymes such as superoxide dismutase. This anti-oxidative vs. oxidative profile may help to explain bat's longer than expected lifespans. The aim of this study was to assess the effect that a significant reduction in flying has on bats leukocytes mitochondrial activity. This was assessed using samples of lymphoid and myeloid cells from peripheral blood from Artibeus jamaicensis bats shortly after capture and up to six weeks after flying deprivation. Mitochondrial membrane potential (Δψm), mitochondrial calcium (mCa2+), and mitochondrial ROS (mROS) were used as key indicators of mitochondrial activity, while total ROS and glucose uptake were used as additional indicators of cell metabolism. Results showed that total ROS and glucose uptake were statistically significantly lower at six weeks of flying deprivation (p < 0.05), in both lymphoid and myeloid cells, however no significant changes in mitochondrial activity associated with flying deprivation was observed (p > 0.05). These results suggest that bat mitochondria are stable to sudden changes in physical activity, at least up to six weeks of flying deprivation. However, decrease in total ROS and glucose uptake in myeloid cells after six weeks of captivity suggest a compensatory mechanism due to the lack of the highly metabolic demands associated with flying.

Multirresistencia en Escherichia coliasociada a Betalactamasas de Espectro Extendido en urocultivos obtenidos en pacientes de una provincia de la Amazonía Peruana / Multiresistance in Escherichia coli associated with Extended Spectrum Beta-lactamases in urine cultures obtained in patients from a province of the Peruvian Amazon

Introducción: Los antibióticos betalactámicos son los más utilizados en el tratamiento de las infecciones urinarias en el Perú. La resistencia bacteriana se produce frecuentemente por la presencia de Betalactamasas de Espectro Extendido (BLEE) en enterobacterias. Objetivo: Determinar la multirresistencia en E. coli asociada a betalactamasas de espectro extendido en urocultivos de adultos que residen en la provincia de Tambopata-Madre De Dios. El estudio: Estudio no experimental, descriptivo, la detección y la confirmación de BLEE se realizó con la técnica de doble disco usando ceftazidima, cefotaxima, cefepime, aztreonam y amoxicilina más ácido clavulánico. La resistencia y susceptibilidad microbiana se identificó usando la técnica de disco de difusión. Hallazgos: Se aislaron 162 cepas de E. coli. Se identificaron cepas con resistencia a los antibióticos ampicilina (71%), trimetoprim sulfametoxazol (49%), ácido ciprofloxacino (37%), ácido nalidíxico (37%) y aztreonam (31%). Conclusión: Existe resistencia antimicrobiana mediada por cepas de E. coli productoras BLEE.

Background:Beta-lactamantibioticsarethemostusedinthe treatment of urinary infections in Peru. Bacterial resistance is frequently produced by the presence of Extended Spectrum Betalactamases (ESBL) in Enterobacteriaceae. To determine the multi-resistance inObjective:E. coliassociated to extended spectrum beta-lactamases in urine cultures from adults residing in the province of Tambopata-Madre De Dios. The study:Non-experimental, descriptive study, detection and confirmation of ESBLwas performed with the double disc technique using ceftazidime, cefotaxime, cefepime, aztreonam and amoxicillin plus clavulanic acid. Microbial resistance and susceptibility was identified using the diffusion disk technique. 162 strains of E. coliwere isolated. Strains Findings:withresistancetotheantibioticsampicillin(71%),trimethoprine sulfamethoxazole (49%), ciprofloxacin acid (37%), nalidixic acid (37%) andaztreonam(31%)wereidentified.Thereis Conclusion:antimicrobial resistance mediated by ESBL-producing strains of E. coli.

The Role of Tricarboxylic Acid Cycle Metabolites in Viral Infections.

Host cell metabolism is essential for the viral replication cycle and, therefore, for productive infection. Energy (ATP) is required for the receptor-mediated attachment of viral particles to susceptible cells and for their entry into the cytoplasm. Host cells must synthesize an array of biomolecules and engage in intracellular trafficking processes to enable viruses to complete their replication cycle. The tricarboxylic acid (TCA) cycle has a key role in ATP production as well as in the synthesis of the biomolecules needed for viral replication. The final assembly and budding process of enveloped viruses, for instance, require lipids, and the TCA cycle provides the precursor (citrate) for fatty acid synthesis (FAS). Viral infections may induce host inflammation and TCA cycle metabolic intermediates participate in this process, notably citrate and succinate. On the other hand, viral infections may promote the synthesis of itaconate from TCA cis-aconitate. Itaconate harbors anti-inflammatory, anti-oxidant, and anti-microbial properties. Fumarate is another TCA cycle intermediate with immunoregulatory properties, and its derivatives such as dimethyl fumarate (DMF) are therapeutic candidates for the contention of virus-induced hyper-inflammation and oxidative stress. The TCA cycle is at the core of viral infection and replication as well as viral pathogenesis and anti-viral immunity. This review highlights the role of the TCA cycle in viral infections and explores recent advances in the fast-moving field of virometabolism.

Epidemiological surveillance of chikungunya fever in Mexico since its introduction in 2014-2016 and identification of circulating genotypes.

In 2014, the chikungunya virus (CHIKV) was detected for the first time in Mexico, the identified strain was the one corresponding to the Asian genotype which was phylogenetically grouped with the strains that circulated in the British Virgin Islands outbreak and was later classified with lineages of Caribbean strains. In three years, 13,569 cases of chikungunya were registered in Mexico. Although the transmission and spread of the virus are now considered a moderate risk, the danger that the virus reemerges is not ruled out due to the infestation of Aedes mosquitoes. In this study, we reviewed the chikungunya fever (CHIKF) cases reported between 2014 and 2016 to reanalyze the data. Seventeen cases were selected from different states where the circulation of the virus had been reported. Statistical data were analyzed and a retrospective analysis was carried out. Nucleic acid sequences were determined of these 17 samples. 2015 was the year with the highest number of cases (92.8%) and they were detected in 28 states of the country. There is a predominance of females, and the most affected age group was between 25 and 44 years. In 2016, CHIKV genotypes were not known, in this study the presence of the Asian genotype of Caribbean lineage was confirmed. The presence of the West African and ECSA genotypes was phylogenetically ruled out. The sequences obtained were deposited in GeneBank.

Mitochondrial Signature in Human Monocytes and Resistance to Infection in C. elegans During Fumarate-Induced Innate Immune Training.

Monocytes can develop immunological memory, a functional characteristic widely recognized as innate immune training, to distinguish it from memory in adaptive immune cells. Upon a secondary immune challenge, either homologous or heterologous, trained monocytes/macrophages exhibit a more robust production of pro-inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, than untrained monocytes. Candida albicans, ß-glucan, and BCG are all inducers of monocyte training and recent metabolic profiling analyses have revealed that training induction is dependent on glycolysis, glutaminolysis, and the cholesterol synthesis pathway, along with fumarate accumulation; interestingly, fumarate itself can induce training. Since fumarate is produced by the tricarboxylic acid (TCA) cycle within mitochondria, we asked whether extra-mitochondrial fumarate has an effect on mitochondrial function. Results showed that the addition of fumarate to monocytes induces mitochondrial Ca2+ uptake, fusion, and increased membrane potential (Δψm), while mitochondrial cristae became closer to each other, suggesting that immediate (from minutes to hours) mitochondrial activation plays a role in the induction phase of innate immune training of monocytes. To establish whether fumarate induces similar mitochondrial changes in vivo in a multicellular organism, effects of fumarate supplementation were tested in the nematode worm Caenorhabditis elegans. This induced mitochondrial fusion in both muscle and intestinal cells and also increased resistance to infection of the pharynx with E. coli. Together, these findings contribute to defining a mitochondrial signature associated with the induction of innate immune training by fumarate treatment, and to the understanding of whole organism infection resistance.

Mitochondria: An Integrative Hub Coordinating Circadian Rhythms, Metabolism, the Microbiome, and Immunity.

There is currently some understanding of the mechanisms that underpin the interactions between circadian rhythmicity and immunity, metabolism and immune response, and circadian rhythmicity and metabolism. In addition, a wealth of studies have led to the conclusion that the commensal microbiota (mainly bacteria) within the intestine contributes to host homeostasis by regulating circadian rhythmicity, metabolism, and the immune system. Experimental studies on how these four biological domains interact with each other have mainly focused on any two of those domains at a time and only occasionally on three. However, a systematic analysis of how these four domains concurrently interact with each other seems to be missing. We have analyzed current evidence that signposts a role for mitochondria as a key hub that supports and integrates activity across all four domains, circadian clocks, metabolic pathways, the intestinal microbiota, and the immune system, coordinating their integration and crosstalk. This work will hopefully provide a new perspective for both hypothesis-building and more systematic experimental approaches.

Comparative leucocyte populations between two sympatric carnivores (Nasua narica and Procyon lotor).

Coatis (Nasua narica) and raccoons (Procyon lotor) potentially play an important role in zoonotic diseases because they may carry pathogens and can transmit them to humans. To date, our understanding of the immune function of these two carnivores is deficient. The aim of this study was to compare the number of leucocyte subtypes and the phagocytic capacity between the coati and the raccoon. Blood samples were collected, and leucocyte subtypes were characterized and counted by flow cytometry and microscopy, respectively. Phagocytosis was analysed by kinetic assay. Differences in leucocytes between these two species were found; the total count of neutrophils was higher in raccoons than in coatis, but lymphocytes and eosinophils were higher in coatis than in raccoons. Antigen reduction was more rapid for the coatis. However, raccoons had a higher efficient endocytic process than coatis. This study provides the basis for understanding the procyonid immune system, which informs conservation, particularly since some procyonids are imperilled.

Virus Control of Cell Metabolism for Replication and Evasion of Host Immune Responses.

Over the last decade, there has been significant advances in the understanding of the cross-talk between metabolism and immune responses. It is now evident that immune cell effector function strongly depends on the metabolic pathway in which cells are engaged in at a particular point in time, the activation conditions, and the cell microenvironment. It is also clear that some metabolic intermediates have signaling as well as effector properties and, hence, topics such as immunometabolism, metabolic reprograming, and metabolic symbiosis (among others) have emerged. Viruses completely rely on their host's cell energy and molecular machinery to enter, multiply, and exit for a new round of infection. This review explores how viruses mimic, exploit or interfere with host cell metabolic pathways and how, in doing so, they may evade immune responses. It offers a brief outline of key metabolic pathways, mitochondrial function and metabolism-related signaling pathways, followed by examples of the mechanisms by which several viral proteins regulate host cell metabolic activity.

LprG and PE_PGRS33 Mycobacterium tuberculosis virulence factors induce differential mitochondrial dynamics in macrophages.

The interaction of a pathogen with its host cell takes place at different levels, including the bioenergetics adaptation of both the pathogen and the host cell in the course of an infection. In this regard, Mycobacterium tuberculosis infection of macrophages induces mitochondrial membrane potential (Δψm) changes and cytochrome c release, depending on the bacteria strain's virulence, and the mitochondrial dynamics is modified by pathogens, such as Listeria monocytogenes. Here, we investigated whether two M. tuberculosis virulence factors are able to induce distinguishable bioenergetics traits in human monocyte-derived macrophages (MDMs). Results showed that Rv1411c (LprG, p27) induced mitochondrial fission, lowered the cell respiratory rate and modified the kinetics of mitochondrial Ca2+ uptake in response to agonist stimulation. In contrast, Rv1818c (PE_PGRS33) induced mitochondrial fusion, but failed to induce any appreciable effect on cell respiratory rate or mitochondrial Ca2+ uptake. Overall, these results suggest that two different virulence factors from the same pathogen (M. tuberculosis) induce differential effects on mitochondrial dynamics, cell respiration and mitochondrial Ca2+ uptake in MDMs. The timing of differential mitochondrial activity could ultimately determine the outcome of host-pathogen interactions.

Eficiência e segurança de secretagogos intestinais para constipação crônica: uma revisão sistemática e meta-análise / Efficacy and safety of intestinal secretagogues for chronic constipation: a systematic review and meta-analysis

ABSTRACT BACKGROUND: Intestinal secretagogues have been tested for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The class-effect of these type of drugs has not been studied. OBJECTIVE: To determine the efficacy and safety of intestinal secretagogues for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. METHODS: A computer-based search of papers from 1966 to September 2017 was performed. Search strategy consisted of the following MESH terms: intestinal secretagogues OR linaclotide OR lubiprostone OR plecanatide OR tenapanor OR chloride channel AND chronic constipation OR irritable bowel syndrome. Data were extracted as intention-to-treat analyses. A random-effects model was used to give a more conservative estimate of the effect of individual therapies, allowing for any heterogeneity among studies. Outcome measures were described as Relative Risk of achieving an improvement in the symptom under consideration. RESULTS: Database Search yielded 520 bibliographic citations: 16 trials were included for analysis, which enrolled 7658 patients. Twelve trials assessed the efficacy of intestinal secretagogues for chronic constipation. These were better than placebo at achieving an increase in the number of complete spontaneous bowel movements per week [RR 1.87 (1.24-2.83)], at achieving three or more spontaneous bowel movements per week [RR 1.56 (1.31-1.85)] and at inducing spontaneous bowel movement after medication intake [RR 1.49 (1.07-2.06)]. Similar results were observed when assessing the efficacy of intestinal secretagogues on constipation-predominant irritable bowel syndrome based on the results of six trials. CONCLUSION: Intestinal secretagogues are useful and safe therapeutic alternatives for the treatment of constipation-related syndromes.

RESUMO CONTEXTO: Os secretagogos intestinais têm sido testados para o tratamento da constipação crônica e síndrome do intestino irritável com constipação predominante. O efeito classe desses tipos de drogas ainda não foi estudado. OBJETIVO: Determinar a eficácia e a segurança de secretagogos intestinais para o tratamento da constipação crônica e síndrome do intestino irritável de constipação predominante. MÉTODOS: Realizada pesquisa baseada em banco de dados de trabalhos publicados entre 1966 e setembro de 2017. A estratégia de pesquisa consistia dos seguintes termos MeSH: secretagogos intestinais OU linaclotide OU lubiprostona OU plecanatide OU tenapanor OU canal de cloro E constipação crônica OU síndrome do intestino irritável. Os dados foram extraídos como análises de intenção de tratar. Um modelo de efeitos aleatórios foi usado para dar uma estimativa mais conservadora do efeito das terapias individuais, permitindo a qualquer heterogeneidade entre os estudos. Os desfechos foram descritos como risco relativo de alcançar uma melhoria no sintoma em consideração. RESULTADOS: A busca no banco de dados rendeu 520 citações bibliográficas: 16 ensaios foram incluídos para análise, que incluiu 7658 pacientes. Doze trabalhos avaliaram a eficácia de secretagogos intestinais para constipação crônica. Estes foram melhores do que placebo, alcançando um aumento no número de evacuações completas espontâneas por semana [RR 1,87 (1,24-2,83)], para a aquisição de três ou mais evacuações espontâneas por semana [RR 1,56 (1,31-1,85)] e na indução espontânea do movimento intestinal após a ingestão de medicação [RR 1,49 (1,07-2,06)]. Resultados semelhantes foram observados ao avaliar a eficácia de secretagogos intestinais na síndrome do intestino irritável de constipação predominante com base em resultados de seis ensaios. CONCLUSÃO: Os secretagogos intestinais são alternativas terapêuticas úteis e seguras para o tratamento de síndromes relacionadas à constipação.

EFFICACY AND SAFETY OF INTESTINAL SECRETAGOGUES FOR CHRONIC CONSTIPATION: A SYSTEMATIC REVIEW AND META-ANALYSIS.

BACKGROUND: Intestinal secretagogues have been tested for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. The class-effect of these type of drugs has not been studied. OBJECTIVE: To determine the efficacy and safety of intestinal secretagogues for the treatment of chronic constipation and constipation-predominant irritable bowel syndrome. METHODS: A computer-based search of papers from 1966 to September 2017 was performed. Search strategy consisted of the following MESH terms: intestinal secretagogues OR linaclotide OR lubiprostone OR plecanatide OR tenapanor OR chloride channel AND chronic constipation OR irritable bowel syndrome. Data were extracted as intention-to-treat analyses. A random-effects model was used to give a more conservative estimate of the effect of individual therapies, allowing for any heterogeneity among studies. Outcome measures were described as Relative Risk of achieving an improvement in the symptom under consideration. RESULTS: Database Search yielded 520 bibliographic citations: 16 trials were included for analysis, which enrolled 7658 patients. Twelve trials assessed the efficacy of intestinal secretagogues for chronic constipation. These were better than placebo at achieving an increase in the number of complete spontaneous bowel movements per week [RR 1.87 (1.24-2.83)], at achieving three or more spontaneous bowel movements per week [RR 1.56 (1.31-1.85)] and at inducing spontaneous bowel movement after medication intake [RR 1.49 (1.07-2.06)]. Similar results were observed when assessing the efficacy of intestinal secretagogues on constipation-predominant irritable bowel syndrome based on the results of six trials. CONCLUSION: Intestinal secretagogues are useful and safe therapeutic alternatives for the treatment of constipation-related syndromes.

Immunization with intestinal microbiota-derived Staphylococcus aureus and Escherichia coli reduces bacteria-specific recolonization of the intestinal tract.

A wide array of microorganisms colonizes distinctive anatomical regions of animals, being the intestine the one that harbors the most abundant and complex microbiota. Phylogenetic analyses indicate that it is composed mainly of bacteria, and that Bacterioidetes and Firmicutes are the most represented phyla (>90% of the total eubacteria) in mice and humans. Intestinal microbiota plays an important role in host physiology, contributing to digestion, epithelial cells metabolism, stimulation of intestinal immune responses, and protection against intestinal pathogens. Changes in its composition may affect intestinal homeostasis, a condition known as dysbiosis, which may lead to non-specific inflammation and disease. The aim of this work was to analyze the effect that a bacteria-specific systemic immune response would have on the intestinal re-colonization by that particular bacterium. Bacteria were isolated and identified from the feces of Balb/c mice, bacterial cell-free extracts were used to immunize the same mice from which bacteria came from. Concurrently with immunization, mice were subjected to a previously described antibiotic-based protocol to eliminate most of their intestinal bacteria. Serum IgG and feces IgA, specific for the immunizing bacteria were determined. After antibiotic treatment was suspended, specific bacteria were orally administered, in an attempt to specifically re-colonize the intestine. Results showed that parenteral immunization with gut-derived bacteria elicited the production of both anti-bacterial IgG and IgA, and that immunization reduces bacteria specific recolonization of the gut. These findings support the idea that the systemic immune response may, at least in part, determine the bacterial composition of the gut.

Assessing global range expansion in a cryptic species complex: insights from the red seaweed genus Asparagopsis (Florideophyceae).

The mitochondrial genetic diversity, distribution and invasive potential of multiple cryptic operational taxonomic units (OTUs) of the red invasive seaweed Asparagopsis were assessed by studying introduced Mediterranean and Hawaiian populations. Invasive behavior of each Asparagopsis OTU was inferred from phylogeographic reconstructions, past historical demographic dynamics, recent range expansion assessments and future distributional predictions obtained from demographic models. Genealogical networks resolved Asparagopsis gametophytes and tetrasporophytes into four A. taxiformis and one A. armata cryptic OTUs. Falkenbergia isolates of A. taxiformis L3 were recovered for the first time in the western Mediterranean Sea and represent a new introduction for this area. Neutrality statistics supported past range expansion for A. taxiformis L1 and L2 in Hawaii. On the other hand, extreme geographic expansion and an increase in effective population size were found only for A. taxiformis L2 in the western Mediterranean Sea. Distribution models predicted shifts of the climatically suitable areas and population expansion for A. armata L1 and A. taxiformis L1 and L2. Our integrated study confirms a high invasive risk for A. taxiformis L1 and L2 in temperate and tropical areas. Despite the differences in predictions among modelling approaches, a number of regions were identified as zones with high invasion risk for A. taxiformis L2. Since range shifts are likely climate-driven phenomena, future invasive behavior cannot be excluded for the rest of the lineages.

In vivo induction of neutrophil extracellular traps by Mycobacterium tuberculosis in a guinea pig model.

In 2004, a novel mechanism of cellular death, called 'NETosis', was described in neutrophils. This mechanism, different from necrosis and apoptosis, is characterized by the release of chromatin webs admixed with microbicidal granular proteins and peptides (NETs). NETs trap and kill a variety of microorganisms. Diverse microorganisms, including Mycobacterium tuberculosis, are NET inducers in vitro. The aim of this study was to examine whether M. tuberculosis can also induce NETs in vivo and if the NETs are bactericidal to the microorganism. Guinea pigs were intradermally inoculated with M. tuberculosis H37Rv, and the production of NETs was investigated at several time points thereafter. NETs were detected as early as 30 min post-inoculation and were clearly evident by 4 h post-inoculation. NETs produced in vivo contained DNA, myeloperoxidase, elastase, histones, ROS and acid-fast bacilli. Viable and heat-killed M. tuberculosis, as well as Mycobacterium bovis BCG were efficient NET inducers, as were unilamellar liposomes prepared with lipids from M. tuberculosis. In vitro, guinea pig neutrophils also produced NETs in response to M. tuberculosis. However, neither the in vivo nor the in vitro-produced NETs were able to kill M. tuberculosis. Nevertheless, in vivo, neutrophils might propitiate recruitment and activation of more efficient microbicidal cells.

Lactate Contribution to the Tumor Microenvironment: Mechanisms, Effects on Immune Cells and Therapeutic Relevance.

Malignant transformation of cells leads to enhanced glucose uptake and the conversion of a larger fraction of pyruvate into lactate, even under normoxic conditions; this phenomenon of aerobic glycolysis is largely known as the Warburg effect. This metabolic reprograming serves to generate biosynthetic precursors, thus facilitating the survival of rapidly proliferating malignant cells. Extracellular lactate directs the metabolic reprograming of tumor cells, thereby serving as an additional selective pressure. Besides tumor cells, stromal cells are another source of lactate production in the tumor microenvironment, whose role in both tumor growth and the antitumor immune response is the subject of intense research. In this review, we provide an integral perspective of the relationship between lactate and the overall tumor microenvironment, from lactate structure to metabolic pathways for its synthesis, receptors, signaling pathways, lactate-producing cells, lactate-responding cells, and how all contribute to the tumor outcome. We discuss the role of lactate as an immunosuppressor molecule that contributes to tumor evasion and we explore the possibility of targeting lactate metabolism for cancer treatment, as well as of using lactate as a prognostic biomarker.

Dengue Virus Serotype-2 Interferes with the Formation of Neutrophil Extracellular Traps.

OBJECTIVES: Neutrophils play an important role in the control of pathogens through several mechanisms, including phagocytosis and the formation of neutrophil extracellular traps (NETs). The latter consists of DNA as a backbone with embedded antimicrobial peptides, histones, and proteases, providing a matrix to entrap and in some cases to kill microbes. Some metabolic requirements for NET formation have recently been described. The virus-induced formation of NETs and the role of these traps in viral infections remain scarcely reported. Here, we analyzed whether dengue virus serotype-2 (DENV-2) induces NET formation and the DENV-2 effect on phorbol myristate acetate (PMA)-induced NETs. METHODS: Peripheral blood-derived neutrophils were exposed in vitro to DENV-2 or exposed to DENV-2 and then stimulated with PMA. NET formation was assessed by fluorescence microscopy. Cell membrane Glut-1, glucose uptake, and reactive oxygen species (ROS) production were assessed. RESULTS: DENV-2 does not induce the formation of NETs. Moreover, DENV-2 inhibits PMA-induced formation of NETs by about 80%. This effect is not related to the production of ROS. The mechanism seemingly accountable for this inhibitory effect is the DENV-2-mediated inhibition of PMA-induced glucose uptake by neutrophils. CONCLUSION: Our results suggest that DENV-2 inhibits glucose uptake as a metabolism-based way to avoid the formation of NETs.

Metabolic requirements for neutrophil extracellular traps formation.

As part of the innate immune response, neutrophils are at the forefront of defence against infection, resolution of inflammation and wound healing. They are the most abundant leucocytes in the peripheral blood, have a short lifespan and an estimated turnover of 10(10) to 10(11) cells per day. Neutrophils efficiently clear microbial infections by phagocytosis and by oxygen-dependent and oxygen-independent mechanisms. In 2004, a new neutrophil anti-microbial mechanism was described, the release of neutrophil extracellular traps (NETs) composed of DNA, histones and anti-microbial peptides. Several microorganisms, bacterial products, as well as pharmacological stimuli such as PMA, were shown to induce NETs. Neutrophils contain relatively few mitochondria, and derive most of their energy from glycolysis. In this scenario we aimed to analyse some of the metabolic requirements for NET formation. Here it is shown that NETs formation is strictly dependent on glucose and to a lesser extent on glutamine, that Glut-1, glucose uptake, and glycolysis rate increase upon PMA stimulation, and that NET formation is inhibited by the glycolysis inhibitor, 2-deoxy-glucose, and to a lesser extent by the ATP synthase inhibitor oligomycin. Moreover, when neutrophils were exposed to PMA in glucose-free medium for 3 hr, they lost their characteristic polymorphic nuclei but did not release NETs. However, if glucose (but not pyruvate) was added at this time, NET release took place within minutes, suggesting that NET formation could be metabolically divided into two phases; the first, independent from exogenous glucose (chromatin decondensation) and, the second (NET release), strictly dependent on exogenous glucose and glycolysis.