The Periplasmic Oxidoreductase DsbA Is Required for Virulence of the Phytopathogen Dickeya solani

In bacteria, the DsbA oxidoreductase is a crucial factor responsible for the introduction of disulfide bonds to extracytoplasmic proteins, which include important virulence factors. A lack of proper disulfide bonds frequently leads to instability and/or loss of protein function; therefore, improper disulfide bonding may lead to avirulent phenotypes. The importance of the DsbA function in phytopathogens has not been extensively studied yet. Dickeya solani is a bacterium from the Soft Rot Pectobacteriaceae family which is responsible for very high economic losses mainly in potato. In this work, we constructed a D. solani dsbA mutant and demonstrated that a lack of DsbA caused a loss of virulence. The mutant bacteria showed lower activities of secreted virulence determinants and were unable to develop disease symptoms in a potato plant. The SWATH-MS-based proteomic analysis revealed that the dsbA mutation led to multifaceted effects in the D. solani cells, including not only lower levels of secreted virulence factors, but also the induction of stress responses. Finally, the outer membrane barrier seemed to be disturbed by the mutation. Our results clearly demonstrate that the function played by the DsbA oxidoreductase is crucial for D. solani virulence, and a lack of DsbA significantly disturbs cellular physiology.

Orally administered antigen can reduce or exacerbate pathology in an animal model of inflammatory arthritis dependent upon the timing of administration

Currently, treatments for rheumatoid arthritis (RA) are focussed on treatment of disease symptoms rather than addressing the cause of disease, which could lead to remission and cure. Central to disease development is the induction of autoimmunity through a breach of self-tolerance. There is considerable research in RA focussed on antigens and approaches to re-establish antigen specific tolerance. A crucial step in this research is to employ appropriate animal models to test prospective antigen specific immunotherapies, preferably in the context of joint inflammation. In this short communication, we use our previously developed model of antigen specific inflammatory arthritis in which OVA-specific TcR tg T cells drive breach of tolerance to endogenous antigens to determine the impact that the timing of therapy administration has upon disease progression. Using antigen feeding to induce tolerance we demonstrate that administration prior to articular challenge results in a reduced disease score as evidenced by pathology and serum antibody responses. By contrast, feeding antigen after articular challenge had the opposite effect and resulted in the exacerbation of pathology. Although preliminary, these data suggest that the timing of antigen administration may be key to the success of tolerogenic immunotherapies. This has important implications for the timing of potential tolerogenic therapies in patients.

Recognition of Human Face Regions under Adverse Conditions—Face Masks and Glasses—In Thermographic Sanitary Barriers through Learning Transfer from an Object Detector

The COVID-19 pandemic has detrimentally affected people’s lives and the economies of many countries, causing disruption in the health, education, transport, and other sectors. Several countries have implemented sanitary barriers at airports, bus and train stations, company gates, and other shared spaces to detect patients with viral symptoms in an effort to contain the spread of the disease. As fever is one of the most recurrent disease symptoms, the demand for devices that measure skin (body surface) temperature has increased. The thermal imaging camera, also known as a thermal imager, is one such device used to measure temperature. It employs a technology known as infrared thermography and is a noninvasive, fast, and objective tool. This study employed machine learning transfer using You Only Look Once (YOLO) to detect the hottest temperatures in the regions of interest (ROIs) of the human face in thermographic images, allowing the identification of a febrile state in humans. The algorithms detect areas of interest in the thermographic images, such as the eyes, forehead, and ears, before analyzing the temperatures in these regions. The developed software achieved excellent performance in detecting the established areas of interest, adequately indicating the maximum temperature within each region of interest, and correctly choosing the maximum temperature among them.

Oxidative ornithine metabolism supports non-inflammatory C. difficile colonization

The enteric pathogen Clostridioides difficile (Cd) is responsible for a toxin-mediated infection that causes more than 200,000 recorded hospitalizations and 13,000 deaths in the United States every year1. However, Cd can colonize the gut in the absence of disease symptoms. Prevalence of asymptomatic colonization by toxigenic Cd in healthy populations is high; asymptomatic carriers are at increased risk of infection compared to noncolonized individuals and may be a reservoir for transmission of Cd infection2,3. Elucidating the molecular mechanisms by which Cd persists in the absence of disease is necessary for understanding pathogenesis and developing refined therapeutic strategies. Here, we show with gut microbiome metatranscriptomic analysis that mice recalcitrant to Cd infection and inflammation exhibit increased community-wide expression of arginine and ornithine metabolic pathways. To query Cd metabolism specifically, we leverage RNA sequencing in gnotobiotic mice infected with two wild-type strains (630 and R20291) and isogenic toxin-deficient mutants of these strains to differentiate inflammation-dependent versus -independent transcriptional states. A single operon encoding oxidative ornithine degradation is consistently upregulated across non-toxigenic Cd strains. Combining untargeted and targeted metabolomics with bacterial and host genetics, we demonstrate that both diet- and host-derived sources of ornithine provide a competitive advantage to Cd, suggesting a mechanism for Cd persistence within a non-inflammatory, healthy gut.

Diagnosis and monitoring of systemic sclerosis-associated interstitial lung disease using high-resolution computed tomography

Patients with systemic sclerosis are at high risk of developing systemic sclerosis–associated interstitial lung disease. Symptoms and outcomes of systemic sclerosis–associated interstitial lung disease range from subclinical lung involvement to respiratory failure and death. Early and accurate diagnosis of systemic sclerosis–associated interstitial lung disease is therefore important to enable appropriate intervention. The most sensitive and specific way to diagnose systemic sclerosis–associated interstitial lung disease is by high-resolution computed tomography, and experts recommend that high-resolution computed tomography should be performed in all patients with systemic sclerosis at the time of initial diagnosis. In addition to being an important screening and diagnostic tool, high-resolution computed tomography can be used to evaluate disease extent in systemic sclerosis–associated interstitial lung disease and may be helpful in assessing prognosis in some patients. Currently, there is no consensus with regards to frequency and scanning intervals in patients at risk of interstitial lung disease development and/or progression. However, expert guidance does suggest that frequency of screening using high-resolution computed tomography should be guided by risk of developing interstitial lung disease. Most experienced clinicians would not repeat high-resolution computed tomography more than once a year or every other year for the first few years unless symptoms arose. Several computed tomography techniques have been developed in recent years that are suitable for regular monitoring, including low-radiation protocols, which, together with other technologies, such as lung ultrasound and magnetic resonance imaging, may further assist in the evaluation and monitoring of patients with systemic sclerosis–associated interstitial lung disease. A video abstract to accompany this article is available at: https://www.globalmedcomms.com/respiratory/Khanna/HRCTinSScILD

Protective immunity induced by oral vaccination with a recombinant Lactococcus lactis vaccine against H5Nx in chickens

Background The development of an influenza vaccine for poultry that provides broadly protective immunity against influenza H5Nx viruses is a challenging goal. Results Lactococcus lactis (L. lactis)/pNZ8149-HA1-M2 expressing hemagglutinin-1 (HA1) of A/chicken/Vietnam/NCVD-15A59/2015 (H5N6) and the conserved M2 gene of A/Vietnam/1203/2004 (H5N1) was generated. L. lactis/pNZ8149-HA1-M2 could induce significant humoral, mucosal and cell-mediated immune responses, as well as neutralization antibodies. Importantly, L. lactis/pNZ8149-HA1-M2 could prevent disease symptoms without significant weight loss and confer protective immunity in a chicken model against lethal challenge with divergent influenza H5Nx viruses, including H5N6 and H5N1. Conclusions L. lactis/pNZ8149-HA1-M2 can serve as a promising vaccine candidate in poultry industry for providing protection against H5Nx virus infection in the field application.

Plant-based dietary changes may improve symptoms in patients with systemic lupus erythematosus

Introduction Previous studies have reported that patients affected by systemic lupus erythematosus (SLE) are interested in using diet to treat fatigue, cardiovascular disease and other symptoms. However, to date, there is insufficient information regarding the ways for patients to modify their diet to improve SLE symptoms. We investigated the relationship between the eating patterns of SLE patients and their self-reported disease symptoms and general aspects of health. Methods A UK-based, online survey was developed, in which patients with SLE were asked about their attitudes and experiences regarding their SLE symptoms and diet. Results The majority (>80%) of respondents that undertook new eating patterns with increased vegetable intake and/or decreased intake of processed food, sugar, gluten, dairy and carbohydrates reported benefiting from their dietary change. Symptom severity ratings after these dietary changes were significantly lower than before (21.3% decrease, p<0.0001). The greatest decreases in symptom severity were provided by low/no dairy (27.1% decrease), low/no processed foods (26.6% decrease) and vegan (26% decrease) eating patterns (p<0.0001). Weight loss, fatigue, joint/muscle pain and mood were the most cited symptoms that improved with dietary change. Conclusion SLE patients who changed their eating patterns to incorporate more plant-based foods while limiting processed foods and animal products reported improvements in their disease symptoms. Thus, our findings show promises in using nutrition interventions for the management of SLE symptoms, setting the scene for future clinical trials in this area. Randomised studies are needed to further test whether certain dietary changes are effective for improving specific symptoms of SLE.