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Objectives: Treatment of infections caused by Acinetobacter baumannii nosocomial strains has become increasingly problematic owing to their resistance to antibiotics. ppGpp is a secondary messenger involved in growth control and various stress responses in bacteria. The mechanism for inhibition of antibiotic resistance via ppGpp is still unidentified in various pathogenic bacteria including A. baumannii. Here, we investigated the effects of ppGpp on efflux pump (EP)-related genes in A. baumannii.Methods: ppGpp-deficient and -complementary strains were constructed by conjugation and we confirmed (p)ppGpp measurements by thin-layer chromatography. We observed that the ppGpp-deficient strain (ΔA1S_0579) showed abnormal stretching patterns by transmission electron microscopy analysis. The MICs of antimicrobial agents for the WT A. baumannii (ATCC 17978), ppGpp-deficient and complementary strains were determined by the Etest and broth dilution assay methods. The expression levels of EP-related genes were determined by quantitative RT-PCR.Results: We observed morphological differences between a ppGpp-deficient strain (ΔA1S_0579) and the WT strain. Dramatic reductions of MICs in the ppGpp-deficient strain compared with the WT were observed for gentamicin (2.6-fold), tetracycline (3.9-fold), erythromycin (4-fold) and trimethoprim (>4-fold). Expression of the EP-related genes abeB (2.8-fold), tet(A) (2.3-fold), adeB (10.0-fold), adeI (9.9-fold), adeJ (11.8-fold) and adeK (14.4-fold) was also decreased in the ppGpp-deficient strain.Conclusions: This study demonstrates that ppGpp regulates EP-related gene expression in A. baumannii, affecting antibiotic susceptibility. To date, treatment for MDR A. baumannii has had no new antimicrobial agents, so the A1S_0579 gene could be a novel therapeutic target for rational drug design by affecting ppGpp production. [ABSTRACT FROM AUTHOR]

• Multiple particle tracking is challenging in synchrotron X-ray images. • Discriminative appearance and neighbouring topology learning are proposed. • A detection recovery method using multi-frame association is proposed. • Our method achieves tracking errors of 7.03% and association errors of 7.22%. Recent research has introduced a novel method of directly monitoring the effects of potential therapies for Cystic Fibrosis (CF) airway disease by quantifying mucociliary transit (MCT). In this method, micron-sized spherical particles are deposited into rodent airways, and synchrotron X-ray images are obtained to quantify the motion of the particles. However, the accurate tracking of these particles is challenging due to low contrast, image noise, and the presence of overlapping particles. Therefore, this paper proposes a novel method for detecting and tracking circular particles and measuring their dynamics. Accurate particle detection is achieved by applying a convolutional neural network (CNN). For robust multi-object tracking, this paper proposes a confidence model utilizing appearance and neighbouring topology learned by linear discriminant analysis. We also propose a detection recovery method using multi-frame association to restore the missed particles due to overlapping. The proposed method is tested with several different datasets and shows high levels of detection and tracking accuracy. Finally, by offering visual tracking analyses that display merging and splitting events, the proposed method can provide a better understanding of airway MCT behaviour. [ABSTRACT FROM AUTHOR]

Cystic Fibrosis is a genetic disease in which the production of thick sticky mucus compromises the mucociliary transit (MCT) system and causes obstruction of the conducting airways. This results in a cycle of inflammation and infection that dramatically reduces quality of life and causes an early death for most. To directly assess airway health and the effects of potential treatments, synchrotron X-ray imaging techniques have been developed to non-invasively quantify MCT, by visualizing the motion of micron-sized spherical particles deposited into the nasal airways of live mice. Since the level of contrast between the target particles and the background is quite low, and the particles often overlap, most existing methods show a low detection accuracy for the MCT tracking particles in these state-of-the-art PCXI images. This paper proposes a new way to automatically detect the circular shapes of micron-sized particles in these low-contrast X-ray images. The proposed algorithm uses a gradient-directional, sectored ring mask, combined with an edge projection into the ring boundary to identify circular shapes. This new algorithm achieves significantly improved marker particle detection rate, 92.1% precision, 93.9% recall and 92.7% F-measurement, compared to existing methods. It can detect a certain degree of overlapping particles that existing methods struggle to achieve. This algorithm provides automatic MCT particle counting, which significantly reduces the manual labelling process for MCT analysis of living animals. [ABSTRACT FROM AUTHOR]

Background: Several genetic studies have been undertaken to elucidate the intricate interplay between genetics and drug responses in bipolar disorder (BD). However, there has been notably limited research on biomarkers specifically linked to valproate, with only a few studies investigating integrated proteomic and genomic factors in response to valproate treatment. Therefore, this study aimed to identify biological markers for the therapeutic response to valproate treatment in BD. Patients with BD in remission were assessed only at baseline, whereas those experiencing acute mood episodes were evaluated at three points (baseline, 8 ± 2 weeks, and 6 ± 1 months). The response to valproate treatment was measured using the Alda scale, with individuals scoring an Alda A score ≥ 5 categorized into the acute-valproate responder (acute-VPAR) group. We analyzed 158 peptides (92 proteins) from peripheral blood samples using multiple reaction monitoring mass spectrometry, and proteomic result-guided candidate gene association analyses, with 1,627 single nucleotide variants (SNVs), were performed using the Korean chip. Results: The markers of 37 peptides (27 protein) showed temporal upregulation, indicating possible association with response to valproate treatment. A total of 58 SNVs in 22 genes and 37 SNVs in 16 genes showed nominally significant associations with the Alda A continuous score and the acute-VPAR group, respectively. No SNVs reached the genome-wide significance threshold; however, three SNVs (rs115788299, rs11563197, and rs117669164) in the secreted phosphoprotein 2 gene reached a gene-based false discovery rate-corrected significance threshold with response to valproate treatment. Significant markers were associated with the pathophysiological processes of bipolar disorders, including the immune response, acute phase reaction, and coagulation cascade. These results suggest that valproate effectively suppresses mechanisms associated with disease progression. Conclusions: The markers identified in this study could be valuable indicators of the underlying mechanisms associated with response to valproate treatment. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii, a major nosocomial pathogen, survives in diverse hospital environments, and its multidrug resistance is a major concern. The ppGpp-dependent stringent response mediates the reprogramming of genes with diverse functions in several bacteria. We investigated whether ppGpp is involved in A. baumannii's pathogenesis by examining biofilm formation, surface motility, adhesion, invasion, and mouse infection studies. Transcriptome analysis of early stationary phase cultures revealed 498 differentially-expressed genes (≥ 2-fold change) in a ppGpp-deficient A. baumannii strain; 220 and 278 genes were up and downregulated, respectively. Csu operon expression, important in pilus biosynthesis during early biofilm formation, was significantly reduced in the ppGpp-deficient strain. Our findings suggest that ppGpp signaling influences A. baumannii biofilm formation, surface motility, adherence, and virulence. We showed the association between ppGpp and pathogenicity in A. baumannii for the first time; ppGpp may be a novel antivirulence target in A. baumannii. [ABSTRACT FROM AUTHOR]

Lactobacillus reuteri AN417 is a newly characterized probiotic strain. The activity of AN417 against oral pathogenic bacteria is unknown. We investigated the antibacterial activity of cell-free L. reuteri AN417 culture supernatant (LRS) against three oral pathogens: Porphyromonas gingivalis, Fusobacterium nucleatum, and Streptococcus mutans. P. gingivalis and F. nucleatum have been implicated in periodontal disease, whereas S. mutans causes dental caries. Exposing these oral pathogenic bacteria to LRS significantly reduced their growth rates, intracellular ATP levels, cell viability, and time-to-kill. The minimal inhibitory volume of LRS was 10% (v/v) against P. gingivalis, 20% (v/v) for F. nucleatum, and 30% (v/v) for S. mutans. LRS significantly reduced the integrity of biofilms and significantly suppressed the expression of various genes involved in P. gingivalis biofilm formation. The L. reuteri AN417 genome lacked genes encoding reuterin, reuteran, and reutericyclin, which are major antibacterial compounds produced in L. reuteri strains. LRS treated with lipase and α-amylase displayed decreased antibacterial activity against oral pathogens. These data suggest that the antibacterial substances in LRS are carbohydrates and/or fatty acid metabolites. Our results demonstrate that LRS has antimicrobial activity against dental pathogenic bacteria, highlighting its potential utility for the prevention and treatment of P. gingivalis periodontal disease. [ABSTRACT FROM AUTHOR]

• Design and prototyping of a multispectral imaging system for industrial food application. • Low cost high speed multispectral imaging system design. • Validation of the process of frequency transfer between hyperspectral and multispectral cameras. The design of a multispectral camera system to replace hyperspectral cameras used in chemometrics laboratory for food research is a challenging task in the field of machine vision. In this paper, the process of designing and prototyping a low cost multispectral camera to measure aflatoxin B 1 in almonds is described. A multispectral system with a Goldeye G-008 TEC1 SWIR is developed to replace a hyperspectral system with a Specim FX17 line scanner. Using R-squared and RMSE values of multiple linear regression, the performance of a hyperspectral camera system with a multispectral camera system were compared for measuring aflatoxin B 1 . The results show that a high speed multispectral system can replace an equivalent hyperspectral imaging system with much lower cost with an acceptable processing performance of 20 datacubes per seconds. [ABSTRACT FROM AUTHOR]