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- ArticleLi JT, Wang H, Li W, Wang LF, Hou LC, Mu JL, Liu X, Chen HJ, Xie KL, Li NL, Gao CF.Mediators Inflamm. 2013;2013:108928.We investigated the effect of 1.4% isoflurane (ISO) on the development of inflammation and apoptosis caused by zymosan (ZY) in mice. We found that ZY-challenged mice exhibited significant body weight loss, markedly high mortality, and significant lung injury characterized by the deterioration of histopathology, histologic scores, and wet-to-dry ratio after ISO treatment. ISO dramatically attenuated ZY-induced lung neutrophil recruitment and inflammation, as evidenced by the reduced levels of total cells, neutrophils, and proinflammatory cytokines (i.e., tumor necrosis factor- α , interleukin- (IL-) 1 β , IL-6, and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid and of their mRNA expression in lung tissues. ISO also inhibited ZY-induced expression and activation of nuclear factor-kappaB p65 and inducible nitric oxide synthase in pulmonary tissue. ZY administration also resulted in the upregulation of heme oxygenase-1 expression and activity in the lung, which was further enhanced by ISO treatment. Moreover, ISO markedly prevented ZY-induced pulmonary cell apoptosis in mice, as reflected by the decrease in expression of procaspase-8, procaspase-3, cleaved caspase-8, and cleaved caspase-3, as well as in caspase-3 activity and Bcl-2-associated X/B-cell lymphoma 2 ratio. These results indicate that ISO is a potential therapeutic drug for treating ZY-induced lung injury, and further investigations are warranted.
- ArticleStahl AN, Racca JM, Kerley CI, Anderson A, Landman B, Hood LJ, Gifford RH, Rex TS.Hear Res. 2024 01;441:108928.Auditory complaints are frequently reported by individuals with mild traumatic brain injury (mTBI) yet remain difficult to detect in the absence of clinically significant hearing loss. This highlights a growing need to identify sensitive indices of auditory-related mTBI pathophysiology beyond pure-tone thresholds for improved hearing healthcare diagnosis and treatment. Given the heterogeneity of mTBI etiology and the diverse peripheral and central processes required for normal auditory function, the present study sought to determine the audiologic assessments sensitive to mTBI pathophysiology at the group level using a well-rounded test battery of both peripheral and central auditory system function. This test battery included pure-tone detection thresholds, word understanding in quiet, sentence understanding in noise, distortion product otoacoustic emissions (DPOAEs), middle-ear muscle reflexes (MEMRs), and auditory evoked potentials (AEPs), including auditory brainstem responses (ABRs), middle latency responses (MLRs), and late latency responses (LLRs). Each participant also received magnetic resonance imaging (MRI). Compared to the control group, we found that individuals with mTBI had reduced DPOAE amplitudes that revealed a compound effect of age, elevated MEMR thresholds for an ipsilateral broadband noise elicitor, longer ABR Wave I latencies for click and 4 kHz tone burst elicitors, longer ABR Wave III latencies for 4 kHz tone bursts, larger MLR Na and Nb amplitudes, smaller MLR Pb amplitudes, longer MLR Pa latencies, and smaller LLR N1 amplitudes for older individuals with mTBI. Further, mTBI individuals with combined hearing difficulty and noise sensitivity had a greater number of deficits on thalamic and cortical AEP measures compared to those with only one/no self-reported auditory symptoms. This finding was corroborated with MRI, which revealed significant structural differences in the auditory cortical areas of mTBI participants who reported combined hearing difficulty and noise sensitivity, including an enlargement of left transverse temporal gyrus (TTG) and bilateral planum polare (PP). These findings highlight the need for continued investigations toward identifying individualized audiologic assessments and treatments that are sensitive to mTBI pathophysiology.
- ArticleCiceri S, Colombo D, Ferraboschi P, Grisenti P, Iannone M, Mori M, Meneghetti F.Steroids. 2021 12;176:108928.Vecuronium bromide (Piperidinium, 1-[(2β,3α,5α,16β,17β)-3,17-bis(acetyloxy)-2-(1-piperidinyl)androstan-16-yl]-1-methyl-, bromide; Norcuron®) has been extensively used in anesthesiology practice as neuromuscular blocking agent since its launch on the market in 1982. However, a detailed crystallographic and NMR analysis of its advanced synthetic intermediates is still lacking. Hence, with the aim of filling this literature gap, vecuronium bromide was prepared starting from the commercially available 3β-hydroxy-5α-androstan-17-one (epiandrosterone), implementing some modifications to a traditional synthetic procedure. A careful NMR study allowed the complete assignment of the 1H, 13C, and 15N NMR signals of vecuronium bromide and its synthetic intermediates. The structural and stereochemical characterization of 2β,16β-bispiperidino-5α-androstane-3α,17β-diol, the first advanced synthetic intermediate carrying all the stereocenters in the final configuration, was described by means of single-crystal X-ray diffraction and Hirshfeld surface analysis, allowing a detailed conformational investigation.
- ArticleChen T, Langer R, Weaver JC.Bioelectrochemistry. 2025 Feb 13:108928.
- ArticleDowling CV, Cevaal PM, Faria M, Johnston ST.Math Biosci. 2022 12;354:108928.Nanoparticles are increasingly employed as a vehicle for the targeted delivery of therapeutics to specific cell types. However, much remains to be discovered about the fundamental biology that dictates the interactions between nanoparticles and cells. Accordingly, few nanoparticle-based targeted therapeutics have succeeded in clinical trials. One element that hinders our understanding of nanoparticle-cell interactions is the presence of heterogeneity in nanoparticle dosage data obtained from standard experiments. It is difficult to distinguish between heterogeneity that arises from stochasticity in nanoparticle-cell interactions, and that which arises from heterogeneity in the cell population. Mathematical investigations have revealed that both sources of heterogeneity contribute meaningfully to the heterogeneity in nanoparticle dosage. However, these investigations have relied on simplified models of nanoparticle internalisation. Here we present a stochastic mathematical model of nanoparticle internalisation that incorporates a suite of relevant biological phenomena such as multistage internalisation, cell division, asymmetric nanoparticle inheritance and nanoparticle saturation. Critically, our model provides information about nanoparticle dosage at an individual cell level. We perform model simulations to examine the influence of specific biological phenomena on the heterogeneity in nanoparticle dosage in the absence of heterogeneity in the cell population. Under certain modelling assumptions, we derive analytic approximations of the nanoparticle dosage distribution. We demonstrate that the analytic approximations are accurate, and show that nanoparticle dosage can be described by a Poisson mixture distribution with rate parameters that are a function of Beta-distributed random variables. We discuss the implications of the analytic results with respect to parameter estimation and model identifiability from standard experimental data. Finally, we highlight extensions and directions for future research.
- ArticlepiR-27222 mediates PM2.5-induced lung cancer by resisting cell PANoptosis through the WTAP/m6A axis.Ma W, Xu L, Wang Y, Chen S, Li D, Huo X, Li R, Zhu X, Chen N, Jin Y, Luo J, Li C, Zhao K, Zheng Y, Han W, Yu D.Environ Int. 2024 Aug;190:108928.PM2.5 pollution has been associated with the incidence of lung cancer, but the underlying mechanism is still unclear. PIWI-interacting RNAs (piRNAs), initially identified in germline cells, have emerged as a novel class of small non-coding RNAs (26 - 32 nucleotides) with diverse functions in various diseases, including cancer. However, the role and mechanism of piRNAs in the development of PM2.5-induced lung cancer remain to be clarified. In the presented study, we used a PM2.5-induced malignant transformation cell model to analyze the change of piRNA profiles. Among the disturbed piRNAs, piR-27222 was identified as an oncogene that inhibited cell death in a m6A-dependent manner. Mechanistically, we found that piR-27222 could deubiquitinate and stabilize eIF4B by directly binding to eIF4B and reducing its interaction with PARK2. The enhanced expression of eIF4B, in turn, promoted the expression of WTAP, leading to increased m6A modification in the Casp8 transcript. Consequently, the stability of Casp8 transcripts was reduced, rendering lung cancer cells resistant to PANoptosis. Collectively, our findings reveal that PM2.5 exposure up-regulated piR-27222 expression, which could affect EIF4B/WTAP/m6A axis, thereby inhibiting PANoptosis of cells and promoting lung cancer. Our study provides new insights into understanding the epigenetic mechanisms underlining PM2.5-induced lung cancer.
- ArticleLamoureux ES, Islamzada E, Wiens MVJ, Matthews K, Duffy SP, Ma H.Data Brief. 2023 Apr;47:108928.Red blood cell (RBC) deformability is a vital biophysical property that dictates the ability of these cells to repeatedly squeeze through small capillaries in the microvasculature. This capability is known to differ between individuals and degrades due to natural aging, pathology, and cold storage. There is great interest in measuring RBC deformability because this parameter is a potential biomarker of RBC quality for use in blood transfusions. Measuring this property from microscopy images would greatly reduce the effort required to acquire this information, as well as improve standardization across different centers. This dataset consists of live cell microscopy images of RBC samples from 10 healthy donors. Each RBC sample is sorted into fractions based on deformability using the microfluidic ratchet device. Each deformability fraction is imaged in microwell plates using a Nikon CFI S Plan Fluor ELWD 40 × objective and a Nikon DS-Qi2 CMOS camera on a Nikon Ti-2E inverted microscope. This data could be reused to develop deep learning algorithms to associate live cell images with cell deformability.
- ArticleMiao BB, Gao D, Hao JP, Li YL, Li L, Wang JB, Xiao XH, Yang CC, Zhang L.Int Immunopharmacol. 2022 Sep;110:108928.Along with the extensive application of radiation in medical, military and other fields, human beings carry a greater risk of exposure to radiation environment that causes a range of physical injure, particularly to the brain in cognition. However, the radiation-associated cognitive disability is poorly understood and there is no effective prevention or long-term treatment. Here, we demonstrate that neurogenesis and neuroinflammation disorder are primarily involved in the pathophysiological basis of irradiation-induced cognitive decline. Furthermore, we discovered that tetrahydroxy stilbene glucoside (TSG), a natural active ingredient from Heshouwu that has been well known for its unique anti-aging effect as the Chinese herb, can be a promising mitigator to improve learning-memory ability by facilitating the neurogenesis in the proliferation and differentiation of the surviving neural progenitor cells via AMPK/Tet2, and attenuating the neuroinflammation in the microglial NLRP3 inflammasomes activation via AMPK in vivo. Additionally, TSG was also revealed to activate AMPK by molecular docking and kinase enzyme system assay in vitro. Taken together, our findings identify TSG, as the AMPK activator, prevents radiation-induced cognitive dysfunction by regulating neurogenesis and neuroinflammation via AMPK/Tet2 in rodents, and represents a very promising candidate for developing drugs that can be used for radiation-associated brain injury.
- ArticleSzalanczy AM, Key CC, Solberg Woods LC.J Nutr Biochem. 2022 03;101:108928.Although obesity has been a longstanding health crisis, the genetic architecture of the disease remains poorly understood. Genome-wide association studies have identified many genomic loci associated with obesity, with genes being enriched in the brain, particularly in the hypothalamus. This points to the role of the central nervous system (CNS) in predisposition to obesity, and we emphasize here several key genes along the satiety signaling pathway involved in genetic susceptibility. Interest has also risen regarding the chronic, low-grade obesity-associated inflammation, with a growing concern toward inflammation in the hypothalamus as a precursor to obesity. Recent studies have found that genetic variation in inflammatory genes play a role in obesity susceptibility, and we highlight here several key genes. Despite the interest in the genetic variants of these pathways individually, there is a lack of research that investigates the relationship between the two. Understanding the interplay between genetic variation in obesity genes enriched in the CNS and inflammation genes will advance our understanding of obesity etiology and heterogeneity, improve genetic risk prediction analyses, and highlight new drug targets for the treatment of obesity. Additionally, this increased knowledge will assist in physician's ability to develop personalized nutrition and medication strategies for combating the obesity epidemic. Though it often seems to present universally, obesity is a highly individual disease, and there remains a need in the field to develop methods to treat at the individual level.
- ArticleCho E, Lou HJ, Kuruvilla L, Calderwood DA, Turk BE.Cell Rep. 2021 03 30;34(13):108928.Flux through the RAF-MEK-ERK protein kinase cascade is shaped by phosphatases acting on the core components of the pathway. Despite being an established drug target and a hub for crosstalk regulation, little is known about dephosphorylation of MEK, the central kinase within the cascade. Here, we identify PPP6C, a phosphatase frequently mutated or downregulated in melanoma, as a major MEK phosphatase in cells exhibiting oncogenic ERK pathway activation. Recruitment of MEK to PPP6C occurs through an interaction with its associated regulatory subunits. Loss of PPP6C causes hyperphosphorylation of MEK at activating and crosstalk phosphorylation sites, promoting signaling through the ERK pathway and decreasing sensitivity to MEK inhibitors. Recurrent melanoma-associated PPP6C mutations cause MEK hyperphosphorylation, suggesting that they promote disease at least in part by activating the core oncogenic pathway driving melanoma. Collectively, our studies identify a key negative regulator of ERK signaling that may influence susceptibility to targeted cancer therapies.
- ArticleHolman BWB, Bekhit AEA, Mao Y, Zhang Y, Hopkins DL.Meat Sci. 2022 Nov;193:108928.The quality, colour, and shelf-life of wet aged grass and grain-fed beef were compared. Striploins (n = 24) were each divided into 6 portions and were assigned to different ageing periods (0, 3, 5, 8, 11, or 14 weeks). Analysis demonstrated that declines in shear force and particle size occurred within the first 3 weeks of ageing. Extended ageing resulted in increases in beef purge and pH; and decreases in total moisture, drip, and cooking loss. The initial grass-fed beef drip (3.1%) and particle sizes (201.0 μm) were higher than for grain-fed beef (1.8% and 145.2 μm, respectively). Total viable counts were > 7 cfu/g after 5 weeks of ageing. Total volatile basic nitrogen was < 15 mg/100 g, even after 14 weeks of ageing. Product line by ageing period interactions affected vitamin E and colour parameters. In conclusion, wet aged beef maintains 'acceptable' microbial loads for 5-8 weeks, irrespective of product line and without any deterioration in its quality.
- ArticleXiong P, Chen J, Zhang Y, Shu L, Shen Y, Gu Y, Liu Y, Guan D, Zheng B, Yang Y.iScience. 2024 Feb 16;27(2):108928.Eosinophilic chronic rhinosinusitis (ECRS) is a distinct subset of chronic rhinosinusitis characterized by heightened eosinophilic infiltration and increased symptom severity, often resisting standard treatments. Traditional diagnosis requires invasive histological evaluation. This study aims to develop predictive models for ECRS based on patient clinical parameters, eliminating the need for invasive biopsy. Utilizing logistic regression with lasso regularization, random forest (RF), gradient-boosted decision tree (GBDT), and deep neural network (DNN), we trained models on common clinical data. The predictive performance was evaluated using metrics such as area under the curve (AUC) for receiver operator characteristics, decision curves, and feature ranking analysis. In a cohort of 437 eligible patients, the models identified peripheral blood eosinophil ratio, absolute peripheral blood eosinophil, and the ethmoidal/maxillary sinus density ratio (E/M) on computed tomography as crucial predictors for ECRS. This predictive model offers a valuable tool for identifying ECRS without resorting to histological biopsy, enhancing clinical decision-making.
- ArticleZahran S, Mushinski D, McElmurry SP, Keyes C.Environ Res. 2020 02;181:108928.In February of 2016, the City of Flint, Michigan commenced the FAST start initiative with the aim "to get the lead out of Flint" by replacing lead and galvanized steel service lines throughout the city. An estimated 29,100 parcels are scheduled for service line replacement (SLR) at an expected cost of $172 million. The lead exposure benefits of SLR are evaluated by analyzing Sentinel data on hundreds of repeatedly sampled homes in Flint from February 16, 2016 to July 21, 2017, comparing water lead (WL) in homes with and without lead service lines. Samples taken from homes with lead service lines were significantly more likely to exceed specified thresholds of WL than homes without lead service lines. Second, regardless of service line material type, sampled homes experienced significant reductions in WL with elapsed time from Flint's switchback to water provided by the Detroit Water and Sewage Department. Third, the risk of exceedance of WL > 15 μg/L was uncorrelated with service line material type. These results are robust to sample restrictions, period stratification, time operations, reference group definitions, and statistical modeling procedures. On the question of what is gained from SLR over optimal corrosion control techniques, we simulated age-specific lead uptake (μg/day) and blood lead levels (μg/dL) for children in Flint at 16 and 90 weeks of elapsed time from Flint's switchback to Detroit water. At 90 weeks from the switchback in water source, the quantity of water lead consumed by children in homes with lead service lines decreased 93%, as compared to 16 weeks. Lead exposure benefits of SLR have declined in time, with modest differences in lead uptake across homes with different service lines. In light of results, policy considerations for Flint and nationwide are discussed.
- ArticleCamino E, Dorrego A, Carvajal KA, Buendia-Andres A, de Juan L, Dominguez L, Cruz-Lopez F.Vet Parasitol. 2019 Nov;275:108928.Equine piroplasmosis (EP) is a tick-borne protozoan disease caused by Theileria equi and/or Babesia caballi. Clinical signs (fever, pale mucosal membranes, jaundice), anemia and hyperbilirubinemia have been associated with the disease. EP is widespread, has a significant economic impact on the equine industry and remains endemic in Spain. This study was carried out with samples belonging to 140 horses residing in Spain and showing common clinical signs of EP. A blood smear microscopic examination and a comparison between the different results obtained by competitive Enzyme-Linked Immunosorbent Assay (cELISA), real-time Polymerase Chain Reaction (PCR) and hematological and biochemical (direct and total bilirubin) screening were conducted. EP positivity rates by cELISA and PCR were 50.7% and 42.9%, respectively, whereas only 9% of the horses were positive in the microscopic analysis. A significantly higher number of B. caballi-positive horses were detected by cELISA than PCR, and Kappa value was higher for T. equi (k = 0.575) than for B. caballi (k = 0.401). For the first time, an association between a high ELISA inhibition percentage (IP) and a positive PCR result for B. caballi was determined. Although most authors have described T. equi as more pathogenic than B. caballi, we found that horses parasitized by B. caballi showed a more severe hemolytic anemia, whereas T. equi infections were mostly associated with leukocytosis. The hemogram and clinical chemistry could guide the veterinary surgeon towards the diagnosis of T. equi or B. caballi since horses showed a significant leukocytosis or anemia and hyperbilirubinemia, respectively; however PCR would be the test of choice in order to confirm the diagnosis. Information about the importance of a correct diagnosis of EP using a combination of techniques is essential in order to allow the early detection of cases and prevent the spread of the disease, as well as to avoid the common practice of treating horses without a laboratory diagnosis.
- ArticleWu P, Rodríguez YY, Hershey BJ, Tadassa Y, Dodd KA, Jia W.Vet Microbiol. 2021 Jan;252:108928.Binary ethylenimine (BEI) has been widely used as a virucide to inactivate viruses. For regulatory exclusion of a select agent, the United States Federal Select Agent Program (FSAP) requires an inactivation procedure that renders a select agent non-viable but allows the select agent to retain antigenic characteristics for future use must be validated, and the inactivated agent must be confirmed by a viability testing. In this curve-based validation study, we examined impacts of BEI concentration, treatment temperature, and time on our in-house inactivation procedures of Foot-and-Mouth Disease Virus (FMDV), Vesicular Stomatitis Virus (VSV), and Swine Vesicular Disease Virus (SVDV). The inactivation efficacy was confirmed by virus titration and 3 consecutive blind passages on the monolayers of susceptible cells. A linear correlation between the virus titer reduction and BEI concentration, treatment time, and temperature was established. The results confirmed our in-house BEI inactivation procedure of two doses of 1.5 mM BEI treatment at 37 °C, 1st dose for 24 h, then 2nd dose for 6 more hours for a total of 30 h BEI contact time, can ensure complete inactivation of FMDV, VSV, and SVDV.
- ArticleFu B, Wang G, Wu M, Li W, Zheng Y, Chu Z, Lv F.Eur J Radiol. 2020 May;126:108928.PURPOSE: To investigate the effective dose (E) and convolution kernel's effects on the detection of pulmonary nodules in different artificial intelligence (AI) software systems.
METHODS: Simulated nodules of various sizes and densities in the Lungman phantom were CT scanned at different levels of E (3 - 5, 1 - 3, 0.5 - 1, and <0.5 mSv) and were reconstructed with different kernels (B30f, B60f, and B80f). The number of nodules and corresponding volumes in different images were detected by four AI software systems (A, B, C, and D). Sensitivity, false positives (FPs), false negatives (FNs), and relative volume error (RVE) were calculated and compared to the aspects of the E and convolution kernel.
RESULTS: System B had the highest median sensitivity (100 %). The median FPs of systems B (1) and D (1) was lower than A (11.5) and C (5). System D had the smallest RVE (13.12 %). When the E was <0.5 mSv, system D's sensitivity decreased, while the FPs and FNs of systems A and B increased significantly (P < 0.05). When the kernel was changed from B80f to B30f, the FPs of system A decreased, while that of system C increased, and the RVE of systems A, B, and C increased (P < 0.05).
CONCLUSION: AI software systems B and D have high detection efficiency under normal or low dose conditions and show better stability. However, the detection efficiency of systems A and C would be affected by the E or convolution kernel, but the E would not affect the volume measurement of four systems. - ArticleMeyers-Pantele SA, Rendina HJ, Talan AJ, Shalhav O, Lammert S, Horvath KJ.Drug Alcohol Depend. 2021 10 01;227:108928.BACKGROUND: Racially diverse sexual minority men (SMM) are disproportionately impacted by the U.S. HIV epidemic. Substance use, particularly stimulant use, may impact viral suppression for SMM living with HIV. The current study sought to characterize patterns of substance use via latent class analysis (LCA) and test associations between those patterns and future viral load outcomes, among SMM living with HIV.
METHODS: Data were drawn from Thrive With Me (TWM), an RCT of an mHealth intervention targeting ART adherence among SMM living with HIV. LCA was performed with six dichotomous indicators of substance use, derived from validated measures and urinalysis results, to determine substance use classes at baseline. Bivariate and multivariable logistic regression models tested associations between baseline substance use classes and HIV viral load 5-months post-baseline.
RESULTS: Among 383 SMM living with HIV, we identified a three-class model of substance use fit best: low probability substance use (81.3 %), high probability hazardous alcohol, marijuana, and cocaine use (7.5 %), and high probability methamphetamine and amphetamine use (11.2 %). Additionally, the high probability amphetamine use class was less likely to be virally suppressed at 5-month follow-up compared to the low probability substance use class [Adjusted Odds Ratio = 3.34, 95 % Confidence Interval = 1.39-7.99, p = .0069].
CONCLUSION: We identified that some patterns of substance use (i.e., methamphetamine and amphetamine use), but possibly not others (e.g., alcohol, marijuana, and cocaine use), are potentially important intervention targets for improving HIV-related outcomes among racially diverse SMM living with HIV. - ArticleWeng Z, Ma L, Li J, Zhou Q, Peng L, Li H, Chen L, Xin Z, Shi L, Qi S, Lu Y.J Neurosci Methods. 2020 12 01;346:108928.BACKGROUND: Spinal glioma is a nervous system tumor that tends to relapse and has no specific prognostic molecular biomarkers. Thus, a stable and reproduceable animal research model of spinal glioma is urgently needed.
NEW METHOD: We established a new in situ tumor xenograft model of spinal glioma using nude mice. In this study, we implanted tumors into the cervical spinal cord of nude mice to mimic the pathological characteristics of the original tumors.
RESULTS: Through anatomical experiments, we found that the cervical lamina of mice was thinner, the intervertebral space was much wider, and the adhesion muscles were more easily separated. According to the examination of spinal cord sections, the best puncture point we identified was located 0.9 mm lateral to the posterior median line at the level of the line between the midpoints of the scapulae and at a depth of 0.9 mm. In the nude mouse xenograft experiment, the implanted tumor tissue retained the pathological characteristics of the original tumor.
COMPARISON WITH EXISTING METHOD(S): This model used the cervical spinal cord as the puncture site and patient-derived primary tumor cells, which has never been performed before. Tumor cells could be injected directly without damaging the lamina. Thus, we could reduce the risk of man-made spinal cord injury and infection and avoid destroying the stability and integrity of the spine.
CONCLUSIONS: This study established a stable and reliable animal model of spinal glioma for further molecular research and targeted therapy development. - ArticleCosta JCCP, Bolívar A, Valero A, Carrasco E, Zurera G, Pérez-Rodríguez F.Food Res Int. 2020 05;131:108928.In this study, the inhibitory capacity of Lactobacillus sakei strain L115 against Listeria monocytogenes has been assayed at 4, 8, 11, 15 and 20 °C in broth culture. Besides, the use of predictive microbiology models for describing growth of both microorganisms in monoculture and coculture has been proposed. A preliminary inhibitory test confirmed the ability of Lb. sakei strain L115 to prevent the growth of a five-strain cocktail of L. monocytogenes. Next, the growth of microorganisms in isolation, i.e. in monoculture, was monitored and kinetic parameters maximum specific growth rate (μsp;max) and maximum population density (Nmax) were estimated by fitting the Baranyi model to recorded data. Inhibition coefficients (α) were calculated for the two kinetic parameters tested (μsp:max and Nmax) to quantify the percentage of reduction of growth when the microorganisms were in coculture in comparison with monoculture. The kinetic parameters were input into three interaction models, developed based on modifications of the Baranyi growth model, namely Jameson effect, new modified version of the Jameson effect and Lotka-Volterra models. Two approaches were utilized for simulation, one using the monoculture μsp;max, under the hypothesis that the growth potential is similar under monoculture and coculture conditions provided the environmental conditions are not modified, and the other one, based on adjusting the monoculture kinetic parameter by applying the corresponding α to reproduce the observed μsp;max under coculture conditions, assuming, in this approach, that the existence of a heterogeneous population can change the growth potential of each microbial population. It was observed that in coculture, μsp;max of L. monocytogenes decreased (e.g., α = 31% at 4 °C) and the Nmax was much lower than that of monoculture (e.g., α = 36% at 4 °C). The best simulation performance was achieved applying α to adjust the estimated monoculture growth rate, with the modified Jameson and Lotka-Volterra models showing better fit to the observed microbial interaction data as demonstrated by the fact that 100% data points fell within the acceptable simulation zone (±0.5 log CFU/mL from the simulated data). More research is needed to clarify the mechanisms of interaction between the microorganisms as well as the role of temperature.
- ArticleHoffmann M, Enczmann J, Balz V, Kummer S, Reinauer C, Döing C, Förtsch K, Welters A, Kohns Vasconcelos M, Mayatepek E, Meissner T, Jacobsen M, Seyfarth J.Clin Immunol. 2022 02;235:108928.High soluble IL-7 receptor (sIL-7R) serum levels and associated single nucleotide polymorphisms in the IL7RA gene were found in autoimmune diseases including type 1 diabetes. Further determinants on sIL-7R and IL-7 availability as well as changes during type 1 diabetes disease course remain elusive. Here we performed multiparameter analysis to identify influential genetic and disease-associated factors on sIL-7R and IL-7 serum levels during type 1 diabetes disease course (239 children) and in healthy controls (101 children). We found higher sIL-7R serum concentrations at type 1 diabetes onset and decreasing levels during therapy whereas IL-7 was only higher in long term patients as compared to controls. Multiple linear regression analyses revealed several factors, including IL7RA SNP rs6897932 and HLA risk haplotypes, influencing sIL-7R levels but not IL-7, which was solely associated with the sIL-7R. This study revealed unexpected complexity in the regulation of the sIL-7R but not for IL-7.