Cyclic AMP is a global virulence regulator governing inter and intrabacterial signalling in Acinetobacter baumannii.

Acinetobacter baumannii is an opportunistic nosocomial pathogen with high morbidity and mortality rates. Current treatment options for this pathogen are limited due to its increasing resistance to last-resort antibiotics. Despite A.

An improved genome editing system for Sphingomonadaceae.

The sphingomonads encompass a diverse group of bacteria within the family , with the presence of sphingolipids on their cell surface instead of lipopolysaccharide as their main common feature. They are particularly interesting for bioremediation purposes due to their ability to degrade or metabolise a variety of recalcitrant organic pollutants. However, research and development on their full bioremediation potential has been hampered because of the limited number of tools available to investigate and modify their genome.

Design, Synthesis, and Investigation of the Pharmacokinetics and Anticancer Activities of Indenoisoquinoline Derivatives That Stabilize the G-Quadruplex in the Promoter and Inhibit Topoisomerase I.

G-quadruplexes are noncanonical four-stranded DNA secondary structures. is a master oncogene and the G-quadruplex formed in the promoter functions as a transcriptional silencer and can be stabilized by small molecules. We have previously revealed a novel mechanism of action for indenoisoquinoline anticancer drugs, dual-downregulation of MYC and inhibition of topoisomerase I.

Disrupting iron homeostasis can potentiate colistin activity and overcome colistin resistance mechanisms in Gram-Negative Bacteria.

Acinetobacter baumannii is a Gram-negative priority pathogen that can readily overcome antibiotic treatment through a range of intrinsic and acquired resistance mechanisms. Treatment of carbapenem-resistant A. baumannii largely relies on the use of colistin in cases where other treatment options have been exhausted.

Artificial sweeteners inhibit multidrug-resistant pathogen growth and potentiate antibiotic activity.

Antimicrobial resistance is one of the most pressing concerns of our time. The human diet is rich with compounds that alter bacterial gut communities and virulence-associated behaviours, suggesting food additives may be a niche for the discovery of novel anti-virulence compounds. Here, we identify three artificial sweeteners, saccharin, cyclamate and acesulfame-K (ace-K), that have a major growth inhibitory effect on priority pathogens.

A high-efficiency scar-free genome-editing toolkit for Acinetobacter baumannii.

Background: The current mutagenesis tools for Acinetobacter baumannii leave selection markers or residual sequences behind, or involve tedious counterselection and screening steps. Furthermore, they are usually adapted for model strains, rather than for MDR clinical isolates.

Objectives: To develop a scar-free genome-editing tool suitable for chromosomal and plasmid modifications in MDR A.

The functional differences between paralogous regulators define the control of the general stress response in Sphingopyxis granuli TFA.

Sphingopyxis granuli TFA is a contaminant degrading alphaproteobacterium that responds to adverse conditions by inducing the general stress response (GSR), an adaptive response that controls the transcription of a variety of genes to overcome adverse conditions. The core GSR regulators (the response regulator PhyR, the anti-σ factor NepR and the σ factor EcfG) are duplicated in TFA, being PhyR1 and PhyR2, NepR1 and NepR2 and EcfG1 and EcfG2. Based on multiple genetic, phenotypical and biochemical evidences including in vitro transcription assays, we have assigned distinct functional features to each paralogue and assessed their contribution to the GSR regulation, dictating its timing and the intensity.

APAP-Induced IκBβ/NFκB Signaling Drives Hepatic Il6 Expression and Associated Sinusoidal Dilation.

Acetaminophen (APAP) overdose results in high morbidity and mortality, with limited treatment options. Increased understanding of the cellular signaling pathways activated in response to toxic APAP exposure is needed to provide insight into novel therapeutic strategies. Toxic APAP exposure induces hepatic nuclear factor kappa B (NFκB) activation.

Pulmonary implications of acetaminophen exposures independent of hepatic toxicity.

Both preclinical and clinical studies have demonstrated that exposures to acetaminophen (APAP) at levels that cause hepatic injury cause pulmonary injury as well. However, whether exposures that do not result in hepatic injury have acute pulmonary implications is unknown. Thus, we sought to determine how APAP exposures at levels that do not result in significant hepatic injury impact the mature lung.

The Acute Hepatic NF-κB-Mediated Proinflammatory Response to Endotoxemia Is Attenuated in Intrauterine Growth-Restricted Newborn Mice.

Intrauterine growth restriction (IUGR) is a relevant predictor for higher rates of neonatal sepsis worldwide and is associated with an impaired neonatal immunity and lower immune cell counts. During the perinatal period, the liver is a key immunological organ responsible for the nuclear factor kappa B (NF-κB)-mediated innate immune response to inflammatory stimuli, but whether this role is affected by IUGR is unknown. Herein, we hypothesized that the newborn liver adapts to calorie-restriction IUGR by inducing changes in the NF-κB signaling transcriptome, leading to an attenuated acute proinflammatory response to intraperitoneal lipopolysaccharide (LPS).

Extracytoplasmic Function σ Factors as Tools for Coordinating Stress Responses.

The ability of bacterial core RNA polymerase (RNAP) to interact with different σ factors, thereby forming a variety of holoenzymes with different specificities, represents a powerful tool to coordinately reprogram gene expression. Extracytoplasmic function σ factors (ECFs), which are the largest and most diverse family of alternative σ factors, frequently participate in stress responses. The classification of ECFs in 157 different groups according to their phylogenetic relationships and genomic context has revealed their diversity.

Lower threshold to NFκB activity sensitizes murine β-cells to streptozotocin.

The β-cell response to injury may be as critical for the development of diabetes as the specific insult. In the current study, we used streptozotocin (STZ) to injure the β-cell in order to study the response with a focus on NFκB. MIN6 cells were exposed to STZ (0.

Taxonomic revision of the genus Trichopoda Berthold, 1827 (Diptera: Tachinidae: Phasiinae), with emphasis on the Neotropical fauna.

Trichopoda Berthold, 1827 is a tachinid genus belonging to the subfamily Phasiinae and natively distributed in the Americas. Species of Phasiinae are parasitoids of Hemiptera, especially Heteroptera, and are greatly important as biological control agents. Trichopoda is included in the "Trichopoda typica" group sensu Sabrosky, along with the genera Eutrichopoda Townsend, 1908 and Ectophasiopsis Townsend, 1915a.

Identification of two fnr genes and characterisation of their role in the anaerobic switch in Sphingopyxis granuli strain TFA.

Sphingopyxis granuli strain TFA is able to grow on the organic solvent tetralin as the only carbon and energy source. The aerobic catabolic pathway for tetralin, the genes involved and their regulation have been fully characterised. Unlike most of the bacteria belonging to the sphingomonads group, this strain is able to grow in anoxic conditions by respiring nitrate, though not nitrite, as the alternative electron acceptor.

Maturation of the Acute Hepatic TLR4/NF-κB Mediated Innate Immune Response Is p65 Dependent in Mice.

Compared to adults, neonates are at increased risk of infection. There is a growing recognition that dynamic qualitative and quantitative differences in immunity over development contribute to these observations. The liver plays a key role as an immunologic organ, but whether its contribution to the acute innate immune response changes over lifetime is unknown.

inflammatory challenge induces an early activation of the hepatic innate immune response in late gestation fetal sheep.

Chorioamnionitis is associated with inflammatory end-organ damage in the fetus. Tissues in direct contact with amniotic fluid drive a pro-inflammatory response and contribute to this injury. However, due to a lack of direct contact with the amniotic fluid, the liver contribution to this response has not been fully characterized.

Two paralogous EcfG σ factors hierarchically orchestrate the activation of the General Stress Response in Sphingopyxis granuli TFA.

Under ever-changing environmental conditions, the General Stress Response (GSR) represents a lifesaver for bacteria in order to withstand hostile situations. In α-proteobacteria, the EcfG-type extracytoplasmic function (ECF) σ factors are the key activators of this response at the transcriptional level. In this work, we address the hierarchical function of the ECF σ factor paralogs EcfG1 and EcfG2 in triggering the GSR in Sphingopyxis granuli TFA and describe the role of EcfG2 as global switch of this response.

CpG-ODN-mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBβ to drive IL1α and IL1β expression.

Sterile inflammation contributes to many pathological states associated with mitochondrial injury. Mitochondrial injury disrupts calcium homeostasis and results in the release of CpG-rich mitochondrial DNA. The role of CpG-stimulated TLR9 innate immune signalling and sterile inflammation is well studied; however, how calcium dyshomeostasis affects this signalling is unknown.

Technical-Tactical Analysis of the Players of the Left and Right Wing in Elite Soccer.

In today's soccer, teams are increasingly better trained both physically and tactically, hence different game styles can be identified and differences between them reduced. However, without an exhaustive analysis of reality, the view can lead to the extraction of erroneous conclusions, and what seems to be a team with a marked offensive profile is a mere illusion, resulting to be a team that develops a perfectly balanced game. In this paper, an analysis of technical-tactical performance of players who occupied both wings in an elite team was made, taking as reference the Spanish national soccer team as the model of international game to imitate in the last decade.

Toxic Acetaminophen Exposure Induces Distal Lung ER Stress, Proinflammatory Signaling, and Emphysematous Changes in the Adult Murine Lung.

Clinical studies have demonstrated a strong association between both acute toxic exposure and the repetitive, chronic exposure to acetaminophen (APAP) with pulmonary dysfunction. However, the mechanisms underlying this association are unknown. Preclinical reports have demonstrated that significant bronchiolar injury occurs with toxic APAP exposure, but very little information exists on how the distal lung is affected.

A new synonym for Robineau-Desvoidy, 1830 (Diptera, Tachinidae), the genus Opsozelia Townsend, 1919, with the description of three new species.

The monotypic tachinid genus Townsend, 1919 (Diptera: Tachinidae) is synonymized with Robineau-Desvoidy 1830, . The single species of , Townsend, 1919, is redescribed as , , based on examination of the holotype from Guyana and additional material from Suriname, Brazil and Paraguay. Three new species of similar to are described from Brazil: , and .

Developmentally Regulated Innate Immune NFκB Signaling Mediates IL-1α Expression in the Perinatal Murine Lung.

Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating premature birth. Importantly, preclinical models have demonstrated that IL-1 receptor antagonism prevents the lung injury and subsequent abnormal development that typically results following perinatal exposure to inflammatory stresses. This receptor is activated by two pro-inflammatory cytokines, IL-1α and IL-1β.

Tachinid Fly Parasitism and Phenology of the Neotropical Red-Shouldered Stink Bug, Thyanta perditor (F.) (Heteroptera: Pentatomidae), on the Wild Host Plant, Bidens pilosa L. (Asteraceae).

Field and laboratory studies were conducted with the Neotropical red-shouldered stink bug Thyanta perditor (F.) (Heteroptera: Pentatomidae) aiming to evaluate parasitism incidence on adults by tachinid flies (Diptera: Tachinidae), which were raised in the laboratory for identification. Egg deposition by flies on adult body surface was mapped.