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MicroPublication Biology 2024In brightfield and fluorescence microscopy, capturing images that show well-focused and immobile microorganisms can be challenging. An agarose-based gel pad reduces the...
In brightfield and fluorescence microscopy, capturing images that show well-focused and immobile microorganisms can be challenging. An agarose-based gel pad reduces the variability of results, especially in conditions like uneven specimen staging, variable fluid dynamics, and Brownian motion that plague conventional wet mount setups. To correct these discrepancies during image acquisition, we analyzed three micropad preparation setups. We tested the quality and consistency of pads and images resulting from each setup. Our examination reveals that improved gel pad flatness is associated with better image quality. Moreover, we observe increased consistency in gel pad construction connected to the use of a 3D-printed setup. These findings highlight the technical benefits arising from incorporating micropad-generating platforms that increase the consistency of results in imaging pipelines. Additionally, our use of a quantitative approach to examine pad flatness suggests its inclusion in quality control pipelines to reduce variation in gel pad construction and image quality over time and between investigators. Finally, our use of a 3D-printed setup coupled with a quantitative downstream routine suggests their application in microscopy experiments that involve model organisms relevant to human health and disease.
PubMed: 38344063
DOI: 10.17912/micropub.biology.001081 -
Frontiers in Immunology 2024Clinical applications of CAR-T cells are limited by the scarcity of tumor-specific targets and are often afflicted with the same on-target/off-tumor toxicities that...
Clinical applications of CAR-T cells are limited by the scarcity of tumor-specific targets and are often afflicted with the same on-target/off-tumor toxicities that plague other cancer treatments. A new promising strategy to enforce tumor selectivity is the use of logic-gated, two-receptor systems. One well-described application is termed Tmod™, which originally utilized a blocking inhibitory receptor directed towards HLA-I target antigens to create a protective NOT gate. Here we show that the function of Tmod blockers targeting non-HLA-I antigens is dependent on the height of the blocker antigen and is generally compatible with small, membrane-proximal targets. We compensate for this apparent limitation by incorporating modular hinge units to artificially extend or retract the ligand-binding domains relative to the effector cell surface, thereby modulating Tmod activator and blocker function. By accounting for structural differences between activator and blocker targets, we developed a set of simple geometric parameters for Tmod receptor design that enables targeting of blocker antigens beyond HLA-I, thereby broadening the applications of logic-gated cell therapies.
Topics: Humans; T-Lymphocytes; Neoplasms; Antigens
PubMed: 38343543
DOI: 10.3389/fimmu.2024.1304765 -
Molecules (Basel, Switzerland) Feb 2024Drug resistance represents one of the great plagues of our time worldwide. This largely limits the treatment of common infections and requires the development of new...
Drug resistance represents one of the great plagues of our time worldwide. This largely limits the treatment of common infections and requires the development of new antibiotics or other alternative approaches. Noteworthy, the indiscriminate use of antibiotics is mostly responsible for the selection of mutations that confer drug resistance to microbes. In this regard, recently, ozone has been raising interest for its unique biological properties when dissolved in natural oils. Ozonated oils have been reported to act in a non-specific way on microorganisms hindering the acquisition of advantageous mutations that result in resistance. Here, we focused on the antimicrobial effect of two commercial olive (OOO) and sunflower seeds (OSO) oils. Nuclear magnetic resonance spectroscopy and thermal analysis showed the change in the chemical composition of the oils after ozonation treatment. Different ozonated oil concentrations were then used to evaluate their antimicrobial profile against , , , , , and by agar diffusion and broth dilution methods. Cytotoxicity was also evaluated in keratinocytes and epithelial cells. Overall, our results revealed that both OOO and OSO showed a potent microbicidal effect, especially against (IC50 = OOO: 0.3 mg/mL and OSO: 0.2 mg/mL) and (IC50 = OOO: 0.4 mg/mL and OSO: 2.8 mg/mL) albeit exerting a certain effect also against and Moreover, both OOO and OSO do not yield any relevant cytotoxic effect at the active concentrations in both cell lines. This indicates that the ozonated oils studied are not toxic for mammalian cells despite exerting a potent antimicrobial effect on specific microorganisms. Therefore, OOO and OSO may be considered to integrate standard therapies in the treatment of common infections, likely overcoming drug resistance issues.
Topics: Animals; Olea; Helianthus; Staphylococcus aureus; Escherichia coli; Anti-Infective Agents; Plant Oils; Oils, Volatile; Anti-Bacterial Agents; Seeds; Microbial Sensitivity Tests; Mammals
PubMed: 38338423
DOI: 10.3390/molecules29030679 -
BMC Infectious Diseases Feb 2024Spontaneous miscarriage, a leading health concern globally, often occurs due to various factors, including infections. Among these, Coxiella burnetii and Brucella spp....
BACKGROUND
Spontaneous miscarriage, a leading health concern globally, often occurs due to various factors, including infections. Among these, Coxiella burnetii and Brucella spp. may have adverse effects on pregnancy outcomes. While previous research has established a link between infections and spontaneous miscarriage, our study aimed specifically to investigate the presence of these two pathogens in abortion samples from women who experienced spontaneous miscarriages in Iran. Our study can add to the existing knowledge by focusing on Iran, a region with a high prevalence of C. burnetii and Brucella spp. As a result, it could provide a better understanding and unique insights into the relationship of these pathogens with spontaneous miscarriages in endemic regions.
METHODS
From March 2021 to March 2022, a total of 728 abortion samples (including placenta and cotyledon) were collected from 409 women who had experienced spontaneous miscarriages in the provinces of Tehran, Fars, and West Azerbaijan in Iran. The specimens included 467 Formalin-Fixed Paraffin-Embedded (FFPE) and 261 fresh frozen samples. After DNA extraction from abortion samples, the quantitative real-time PCR (qPCR) assay targeted a specific fragment of the IS1111 and IS711 elements for molecular identification of C. burnetii and Brucella spp., respectively. Furthermore, the qPCR assay employing specific primers for different species was used to determine the species of Brucella.
RESULTS
Among the studied women, 1 out of 409 (0.24%) samples tested positive for Brucella spp., specifically Brucella melitensis. There were no positive specimens for C. burnetii.
CONCLUSIONS
Our study contributes to understanding the potential involvement of Brucella species in spontaneous infectious abortion within endemic regions. The identification of B. melitensis in this study highlights the need for further research in this area. However, while our results suggest a relatively low or zero identification of these pathogens in our sample population, this does not rule out the possibility of undetected infections. Therefore, it is critical to acknowledge the limitations of the molecular techniques used (qPCR), which may have potential limitations such as sensitivity and specificity. Moreover, because 64.15% of our samples were FFPE, the sensitivity of the qPCR test may be reduced. These raise concerns about the accuracy of the reported prevalence rates and the potential for false positives or negatives.
Topics: Humans; Pregnancy; Female; Coxiella burnetii; Abortion, Spontaneous; Iran; Brucellosis; Brucella melitensis; Q Fever
PubMed: 38326756
DOI: 10.1186/s12879-024-09041-5 -
Frontiers in Neuroscience 2023Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms...
INTRODUCTION
Gulf War Illness (GWI), also called Chronic Multisymptom Illness (CMI), is a multi-faceted condition that plagues an estimated 250,000 Gulf War (GW) veterans. Symptoms of GWI/CMI include fatigue, pain, and cognitive dysfunction. We previously reported that 12% of a convenience sample of middle aged (median age 52 years) GW veterans met criteria for mild cognitive impairment (MCI), a clinical syndrome most prevalent in older adults (e.g., ≥70 years). The current study sought to replicate and extend this finding.
METHODS
We used the actuarial neuropsychological criteria and the Montreal Cognitive Assessment (MoCA) to assess the cognitive status of 952 GW veterans. We also examined regional brain volumes in a subset of GW veterans ( = 368) who had three Tesla magnetic resonance images (MRIs).
RESULTS
We replicated our previous finding of a greater than 10% rate of MCI in four additional cohorts of GW veterans. In the combined sample of 952 GW veterans (median age 51 years at time of cognitive testing), 17% met criteria for MCI. Veterans classified as MCI were more likely to have CMI, history of depression, and prolonged (≥31 days) deployment-related exposures to smoke from oil well fires and chemical nerve agents compared to veterans with unimpaired and intermediate cognitive status. We also replicated our previous finding of hippocampal atrophy in veterans with MCI, and found significant group differences in lateral ventricle volumes.
DISCUSSION
Because MCI increases the risk for late-life dementia and impacts quality of life, it may be prudent to counsel GW veterans with cognitive dysfunction, CMI, history of depression, and high levels of exposures to deployment-related toxicants to adopt lifestyle habits that have been associated with lowering dementia risk. With the Food and Drug Administration's recent approval of and the VA's decision to cover the cost for anti-amyloid β (Aβ) therapies, a logical next step for this research is to determine if GW veterans with MCI have elevated Aβ in their brains.
PubMed: 38318196
DOI: 10.3389/fnins.2023.1301066 -
China CDC Weekly Jan 2024Plague is a zoonotic disease that occurs naturally in specific geographic areas. Climate change can influence the populations of the plague host or vector, leading to...
INTRODUCTION
Plague is a zoonotic disease that occurs naturally in specific geographic areas. Climate change can influence the populations of the plague host or vector, leading to variations in the occurrence and epidemiology of plague in animals.
METHODS
In this study, we collected meteorological and plague epidemiological data from the plague focus in the Altun Mountains of the Qinghai-Xizang Plateau. The data spanned from 2000 to 2022. We describe the climatic factors and plague epidemic conditions and we describe their analysis by Pearson's correlation.
RESULTS
During the period from 2000 to 2022, the isolation rates of () from marmots and fleas were 9.27% (451/4,864) and 7.17% (118/1,646), respectively. Additionally, we observed a positive rate of F1 antibody of 11.25% (443/3,937) in marmots and 18.16% (142/782) in dogs. With regards to climate, there was little variation, and a decreasing trend in blowing-sand days was observed. The temperature in the previous year showed a negative correlation with the isolation rate in marmots (r=-0.555, =0.011) and the positive rate of F1 antibody in marmots (r=-0.552, =0.012) in the current year. The average annual precipitation in the previous two years showed a positive correlation with marmot density (r=0.514, =0.024), while blowing-sand days showed a negative correlation with marmot density (r=-0.701, =0.001). Furthermore, the average annual precipitation in the previous three years showed a positive correlation with the isolation rate of from marmots (r=0.666, =0.003), and blowing-sand days showed a negative correlation with marmot density (r=-0.597, =0.009).
CONCLUSIONS
The findings of this study indicate that there is a hysteresis effect of climate change on the prevalence of plague. Therefore, monitoring climate conditions can offer significant insights for implementing timely preventive and control measures to combat plague epidemics.
PubMed: 38313817
DOI: 10.46234/ccdcw2024.015 -
Cureus Dec 2023The revised National Tuberculosis (TB) Control Program is an initiative undertaken by the government of India and was active from 1997 to 2020. Later it was renamed as... (Review)
Review
The revised National Tuberculosis (TB) Control Program is an initiative undertaken by the government of India and was active from 1997 to 2020. Later it was renamed as National TB Elimination Program, which eyes the complete eradication of TB by 2025. The revised National Tuberculosis Control Programme (RNTCP) is preceded by the National TB Control Program which was activated when the cases of TB were on the rise in the early 1960s and police intervention was needed. National Tobacco Control Cell (NTCP) guided the efforts until 1997 when various shortcomings, which were registered over the course of time, were addressed and the revised program was launched. It has been a mixed success as beneficiaries belonging to the reachable, urban areas were benefitted, and tribal, and backward areas were lagging behind. Although the RNTCP proved to be effective in containing TB and curing it to a certain extent, the successor of the program, which is NTEP, has set an ambitious goal of eradicating TB by 2025 which needs concerted efforts on behalf of all stakeholders.
PubMed: 38299135
DOI: 10.7759/cureus.51418 -
BioRxiv : the Preprint Server For... Jan 2024, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded...
, one of the deadliest bacterial pathogens ever known, is responsible for three plague pandemics and several epidemics, with over 200 million deaths during recorded history. Due to high genomic plasticity, is amenable to genetic mutations as well as genetic engineering that can lead to the emergence or intentional development of pan-drug resistant strains. The dissemination of such strains could be catastrophic, with public health consequences far more daunting than those caused by the recent COVID-19 pandemic. Thus, there is an urgent need to develop novel, safe, and effective treatment approaches for managing infections. This includes infections by antigenically distinct strains for which vaccines, none FDA approved yet, may not be effective, and those that cannot be controlled by approved antibiotics. Lytic bacteriophages provide one such alternative approach. In this study, we examined post-exposure efficacy of a bacteriophage cocktail, YPP-401, to combat pneumonic plague caused by CO92. YPP-401 is a four-phage preparation with a 100% lytic activity against a panel of 68 genetically diverse strains. Using a pneumonic plague aerosol challenge model in gender-balanced Brown Norway rats, YPP-401 demonstrated ∼88% protection when delivered 18 hours post-exposure for each of two administration routes (i.e., intraperitoneal and intranasal) in a dose-dependent manner. Our studies suggest that YPP-401 could provide an innovative, safe, and effective approach for managing infections, including those caused by naturally occurring or intentionally developed strains that cannot be managed by vaccines in development and antibiotics.
PubMed: 38293171
DOI: 10.1101/2024.01.17.576055 -
Scientific Data Jan 2024Event-based cameras are commonly leveraged to mitigate issues such as motion blur, low dynamic range, and limited time sampling, which plague conventional cameras....
Event-based cameras are commonly leveraged to mitigate issues such as motion blur, low dynamic range, and limited time sampling, which plague conventional cameras. However, a lack of dedicated event-based datasets for benchmarking segmentation algorithms, especially those offering critical depth information for occluded scenes, has been observed. In response, this paper introduces a novel Event-based Segmentation Dataset (ESD), a high-quality event 3D spatial-temporal dataset designed for indoor object segmentation within cluttered environments. ESD encompasses 145 sequences featuring 14,166 manually annotated RGB frames, along with a substantial event count of 21.88 million and 20.80 million events from two stereo-configured event-based cameras. Notably, this densely annotated 3D spatial-temporal event-based segmentation benchmark for tabletop objects represents a pioneering initiative, providing event-wise depth, and annotated instance labels, in addition to corresponding RGBD frames. By releasing ESD, our aim is to offer the research community a challenging segmentation benchmark of exceptional quality.
PubMed: 38272894
DOI: 10.1038/s41597-024-02920-1 -
PLoS Pathogens Jan 2024Subverting the host immune response to inhibit inflammation is a key virulence strategy of Yersinia pestis. The inflammatory cascade is tightly controlled via the...
Subverting the host immune response to inhibit inflammation is a key virulence strategy of Yersinia pestis. The inflammatory cascade is tightly controlled via the sequential action of lipid and protein mediators of inflammation. Because delayed inflammation is essential for Y. pestis to cause lethal infection, defining the Y. pestis mechanisms to manipulate the inflammatory cascade is necessary to understand this pathogen's virulence. While previous studies have established that Y. pestis actively inhibits the expression of host proteins that mediate inflammation, there is currently a gap in our understanding of the inflammatory lipid mediator response during plague. Here we used the murine model to define the kinetics of the synthesis of leukotriene B4 (LTB4), a pro-inflammatory lipid chemoattractant and immune cell activator, within the lungs during pneumonic plague. Furthermore, we demonstrated that exogenous administration of LTB4 prior to infection limited bacterial proliferation, suggesting that the absence of LTB4 synthesis during plague contributes to Y. pestis immune evasion. Using primary leukocytes from mice and humans further revealed that Y. pestis actively inhibits the synthesis of LTB4. Finally, using Y. pestis mutants in the Ysc type 3 secretion system (T3SS) and Yersinia outer protein (Yop) effectors, we demonstrate that leukocytes recognize the T3SS to initiate the rapid synthesis of LTB4. However, several Yop effectors secreted through the T3SS effectively inhibit this host response. Together, these data demonstrate that Y. pestis actively inhibits the synthesis of the inflammatory lipid LTB4 contributing to the delay in the inflammatory cascade required for rapid recruitment of leukocytes to sites of infection.
Topics: Humans; Animals; Mice; Yersinia pestis; Plague; Type III Secretion Systems; Leukotriene B4; Leukocytes; Inflammation; Bacterial Proteins
PubMed: 38271464
DOI: 10.1371/journal.ppat.1011280