Cytomegalovirus (CMV) infection has a significant impact in patients after allogeneic hematopoietic stem cell transplantation (HSCT). We investigated natural killer (NK) cell reconstitution and ...cytotoxic/cytokine production in controlling CMV infection, especially severe CMV disease in HSCT patients. Fifty-eight patients with acute myeloid leukemia (AML) who received allo-HSCT were included. We monitored NK reconstitution and NK function at baseline, 30, 60, 90, 120, 150, and 180 days after HSCT, and compared the results in recipients stratified on post-HSCT CMV reactivation (
23), non-reactivation (
24) versus CMV disease (
11) groups. The CMV disease group had a significantly delayed recovery of CD56dim NK cells and expansion of FcRγ-CD3ζ+NK cells started post-HSCT 150 days. Sequential results of NK cytotoxicity, NK cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC), and NK-Interferon-gamma (NK-IFNγ) production for 180 days demonstrated delayed recovery and decreased levels in the CMV disease group compared with the other groups. The results within 1 month after CMV viremia also showed a significant decrease in NK function in the CMV disease group compared to the CMV reactivation group. It suggests that NK cells' maturation and cytotoxic/IFNγ production contributes to CMV protection, thereby revealing the NK phenotype and functional NK monitoring as a biomarker for CMV risk prediction, especially CMV disease.
Milk gangliosides have gained considerable attention because they participate in diverse biological processes, including neural development, pathogen binding, and activation of the immune system. ...Herein, we present a quantitative measurement of the gangliosides present in bovine milk and other dairy products and byproducts. Ultrahigh performance liquid chromatography separation was used for high-throughput analysis and achieved a short running time without sacrificing chromatographic resolution. Dynamic multiple reaction monitoring was conducted for 12 transitions for GM3 and 12 transitions for GD3. Transitions to sialic acid fragments (m/z 290.1) were chosen for the quantitation. There was a considerable amount of gangliosides in day 2 milk (GM3, 0.98 mg/L; GD3, 15.2 mg/L) which dramatically decreased at day 15 and day 90. GM3 and GD3 were also analyzed in pooled colostrum, colostrum cream, colostrum butter, and colostrum buttermilk. The separation and analytical approaches here proposed could be integrated into the dairy industry processing adding value to side-streams.
Alzheimer's disease (AD) is a brain disorder manifested by a gradual decline in cognitive function due to the accumulation of extracellular amyloid plaques, disruptions in neuronal substance ...transport, and the degeneration of neurons. In affected neurons, incomplete clearance of toxic proteins by neighboring microglia leads to irreversible brain inflammation, for which cellular signaling is poorly understood. Through single-cell transcriptomic analysis, we discovered distinct regional differences in the ability of microglia to clear damaged neurites. Specifically, microglia in the septal region of wild type mice exhibited a transcriptomic signature resembling disease-associated microglia (DAM). These lateral septum (LS)-enriched microglia were associated with dense axonal bundles originating from the hippocampus. Further transcriptomic and proteomic approaches revealed that primary cilia, small hair-like structures found on cells, played a role in the regulation of microglial secretory function. Notably, primary cilia were transiently observed in microglia, and their presence was significantly reduced in microglia from AD mice. We observed significant changes in the secretion and proteomic profiles of the secretome after inhibiting the primary cilia gene intraflagellar transport particle 88 (Ift88) in microglia. Intriguingly, inhibiting primary cilia in the septal microglia of AD mice resulted in the expansion of extracellular amyloid plaques and damage to adjacent neurites. These results indicate that DAM-like microglia are present in the LS, a critical target region for hippocampal nerve bundles, and that the primary ciliary signaling system regulates microglial secretion, affecting extracellular proteostasis. Age-related primary ciliopathy probably contributes to the selective sensitivity of microglia, thereby exacerbating AD. Targeting the primary ciliary signaling system could therefore be a viable strategy for modulating neuroimmune responses in AD treatments.
The PE and PPE multigene families of Mycobacterium tuberculosis comprise about 10% of the coding potential of the genome. The function of the proteins encoded by these large gene families remains ...unknown, although they have been proposed to be involved in antigenic variation and disease pathogenesis. Interestingly, some members of the PE and PPE families are associated with the ESAT-6 (esx) gene cluster regions, which are regions of immunopathogenic importance, and encode a system dedicated to the secretion of members of the potent T-cell antigen ESAT-6 family. This study investigates the duplication characteristics of the PE and PPE gene families and their association with the ESAT-6 gene clusters, using a combination of phylogenetic analyses, DNA hybridization, and comparative genomics, in order to gain insight into their evolutionary history and distribution in the genus Mycobacterium.
The results showed that the expansion of the PE and PPE gene families is linked to the duplications of the ESAT-6 gene clusters, and that members situated in and associated with the clusters represent the most ancestral copies of the two gene families. Furthermore, the emergence of the repeat protein PGRS and MPTR subfamilies is a recent evolutionary event, occurring at defined branching points in the evolution of the genus Mycobacterium. These gene subfamilies are thus present in multiple copies only in the members of the M. tuberculosis complex and close relatives. The study provides a complete analysis of all the PE and PPE genes found in the sequenced genomes of members of the genus Mycobacterium such as M. smegmatis, M. avium paratuberculosis, M. leprae, M. ulcerans, and M. tuberculosis.
This work provides insight into the evolutionary history for the PE and PPE gene families of the mycobacteria, linking the expansion of these families to the duplications of the ESAT-6 (esx) gene cluster regions, and showing that they are composed of subgroups with distinct evolutionary (and possibly functional) differences.
Iodine is an essential component of thyroid hormones, but excessive iodine intake can lead to thyroid dysfunction. Traditionally, Korean mothers consume brown seaweed soup (miyeokguk), a high source ...of iodine, after childbirth. There is controversy regarding the effects of excessive postpartum iodine intake on the health of mothers and infants. Thus far, there have been no nationwide large-scale surveys regarding the status of iodine intake among postpartum women in Korea. Therefore, we conducted a nationwide survey of postpartum dietary iodine intake among Korean women. In total, 1054 Korean women aged ≥19 years, at less than 8 weeks postpartum, participated in this survey. Dietary data were collected using self-reported 2-day dietary records, along with before-and-after meal photos. To evaluate the correlation between dietary iodine and urinary iodine excretion (UIE), spot urine, and 24 h urine samples were collected from 98 and 29 participants, respectively. The mean daily iodine intake among all participants was 2945.6 μg, and it gradually decreased over time after childbirth. Dietary iodine intake was significantly correlated with 24 h UIE (r = 0.396, p < 0.05) and spot urine UIE (r = 0.312, p < 0.05). Follow-up studies are required to examine the influence of excessive postpartum iodine intake on thyroid health in mothers and their infants.
•The MicroIDSys Elite system evaluated for mycobacterial identification from liquid medium.•High accuracy (98.4%) for detection of 63 reference strains.•Prospective performance evaluation analyzed ...using 167 paired cultures.•>85% correct identification of isolates from both primary cultures and subcultures.
We evaluated the performance of the MicroIDSys Elite system, a newly developed matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry system for identification of mycobacteria directly from positive MGIT liquid cultures.
Analytical specificity was evaluated with 63 reference strains grown in mycobacteria growth indicator tube media. Prospective performance evaluation was conducted with primary liquid cultures of sputum samples for identification of mycobacteria, and results were compared to multigenerational sequencing as the reference method. Liquid media subcultures were also analyzed.
The accuracy for the 63 reference strains was 98.4% (62/63). A total of 167 paired mycobacterial primary cultures and subcultures in liquid media, comprised of seven Mycobacterium tuberculosis isolates, 109 slowly growing nontuberculous mycobacterial isolates, and 51 rapidly growing nontuberculous mycobacterial isolates, was identified by the MicroIDSys Elite system. Using primary liquid cultures, the MicroIDSys Elite system correctly identified 143 (85.6%) isolates; 21 (12.6%) resulted in “no identification”; and three (1.8%) isolates were misidentified. Using liquid media subcultures with this system, 159 (95.2%) isolates were correctly identified; seven (4.2%) resulted in “no identification”; and one (0.6%) isolate was misidentified.
The MicroIDSys Elite system is a useful routine diagnostic tool for identification of mycobacterial species from liquid culture.
Abstract
Pre- and post-transplantation anti-MICA antibody detection development are associated with an increased rejection risk and low graft survival. We previously generated HLA class I null ...HEK-293T using CRISPR/Cas9, while MICA and MICB genes were removed in this study. A panel of 11 cell lines expressing single MICA alleles was established. Anti-MICA antibody in the sera of kidney transplant patients was determined using flow cytometric method (FCM) and the Luminex method. In the 44 positive sera, the maximum FCM value was 2879 MFI compared to 28,135 MFI of Luminex method. Eleven sera (25%) were determined as positive by FCM and 32 sera (72%) were positive by the Luminex method. The sum of total MICA antigens, MICA*002, *004, *009, *019, and *027 correlation showed a statistically significant between the two methods (
P
= 0.0412,
P
= 0.0476,
P
= 0.0019,
P
= 0.0098,
P
= 0.0467, and
P
= 0.0049). These results demonstrated that HEK-293T-based engineered cell lines expressing single MICA alleles were suitable for measuring specific antibodies against MICA antigens in the sera of transplant patients. Studies of antibodies to MICA antigens may help to understand responses in vivo and increase clinical relevance at the cellular level such as complement-dependent cytotoxicity.
This study describes the epidemiological characteristics of coronavirus disease 2019 (COVID-19) based on reported cases from long-term care facilities. As of April 20
th
, 2020, 3 long-term care ...facilities in a metropolitan area of South Korea had reported cases of COVID-19. These facilities’ employees were presumed to be the sources of infection. There were 2 nursing hospitals that did not report any additional cases. One nursing home had a total of 25 cases, with an attack rate of 51.4% (95% CI 35.6–67.0), and a fatality rate of 38.9% (95% CI 20.3–61.4) among residents. The results from this study suggest that early detection and maintenance of infection control minimizes the risk of rapid transmission.
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