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Article ; Online: Lipidomic analysis links mycobactin synthase K to iron uptake and virulence in M. tuberculosis.

Madigan, Cressida A / Martinot, Amanda Jezek / Wei, Jun-Rong / Madduri, Ashoka / Cheng, Tan-Yun / Young, David C / Layre, Emilie / Murry, Jeffrey P / Rubin, Eric J / Moody, D Branch

PLoS pathogens

2015 Volume 11, Issue 3, Page(s) e1004792

Abstract: The prolonged survival of Mycobacterium tuberculosis (M. tb) in the host fundamentally depends on scavenging essential nutrients from host sources. M. tb scavenges non-heme iron using mycobactin and carboxymycobactin siderophores, synthesized by ... ...

Abstract	The prolonged survival of Mycobacterium tuberculosis (M. tb) in the host fundamentally depends on scavenging essential nutrients from host sources. M. tb scavenges non-heme iron using mycobactin and carboxymycobactin siderophores, synthesized by mycobactin synthases (Mbt). Although a general mechanism for mycobactin biosynthesis has been proposed, the biological functions of individual mbt genes remain largely untested. Through targeted gene deletion and global lipidomic profiling of intact bacteria, we identify the essential biochemical functions of two mycobactin synthases, MbtK and MbtN, in siderophore biosynthesis and their effects on bacterial growth in vitro and in vivo. The deletion mutant, ΔmbtN, produces only saturated mycobactin and carboxymycobactin, demonstrating an essential function of MbtN as the mycobactin dehydrogenase, which affects antigenicity but not iron uptake or M. tb growth. In contrast, deletion of mbtK ablated all known forms of mycobactin and its deoxy precursors, defining MbtK as the essential acyl transferase. The mbtK mutant showed markedly reduced iron scavenging and growth in vitro. Further, ΔmbtK was attenuated for growth in mice, demonstrating a non-redundant role of hydroxamate siderophores in virulence, even when other M. tb iron scavenging mechanisms are operative. The unbiased lipidomic approach also revealed unexpected consequences of perturbing mycobactin biosynthesis, including extreme depletion of mycobacterial phospholipids. Thus, lipidomic profiling highlights connections among iron acquisition, phospholipid homeostasis, and virulence, and identifies MbtK as a lynchpin at the crossroads of these phenotypes.
MeSH term(s)	Animals ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Iron/metabolism ; Mice ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/metabolism ; Mycobacterium tuberculosis/pathogenicity ; Oxazoles/metabolism ; Virulence Factors/genetics ; Virulence Factors/metabolism
Chemical Substances	Bacterial Proteins ; Oxazoles ; Virulence Factors ; mycobactins ; Iron (E1UOL152H7)
Language	English
Publishing date	2015-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7366
ISSN (online)	1553-7374
ISSN	1553-7366
DOI	10.1371/journal.ppat.1004792
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Mitochondrial dynamics: updates and perspectives.

Zhang, Kezhong / Petr, Ježek

Scientific reports

2024 Volume 14, Issue 1, Page(s) 9936

MeSH term(s)	Mitochondrial Dynamics ; Humans ; Mitochondria/metabolism ; Animals
Language	English
Publishing date	2024-04-30
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-59998-1
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Article ; Online: Expression of Androgen and Estrogen Receptors in the Human Lacrimal Gland.

Hat, Koraljka / Planinić, Ana / Ježek, Davor / Kaštelan, Snježana

International journal of molecular sciences

2023 Volume 24, Issue 6

Abstract: Lacrimal gland dysfunction causes dry eye disease (DED) due to decreased tear production. Aqueous-deficient DED is more prevalent in women, suggesting that sexual dimorphism of the human lacrimal gland could be a potential cause. Sex steroid hormones are ...

Abstract	Lacrimal gland dysfunction causes dry eye disease (DED) due to decreased tear production. Aqueous-deficient DED is more prevalent in women, suggesting that sexual dimorphism of the human lacrimal gland could be a potential cause. Sex steroid hormones are a key factor in the development of sexual dimorphism. This study aimed to quantify estrogen receptor (ER) and androgen receptor (AR) expression in the human lacrimal gland and compare it between sexes. RNA was isolated from 35 human lacrimal gland tissue samples collected from 19 cornea donors. AR, ERα, and ERβ mRNA was identified in all samples, and their expression was quantified using qPCR. Immunohistochemical staining was performed on selected samples to evaluate protein expression of the receptors. ERα mRNA expression was significantly higher than the expression of AR and ERβ. No difference in sex steroid hormone (SSH) receptor mRNA expression was observed between sexes, and no correlation was observed with age. If ERα protein expression is found to be concordant with mRNA expression, it should be investigated further as a potential target for hormone therapy of DED. Further research is needed to elucidate the role of sex steroid hormone receptors in sex-related differences of lacrimal gland structure and disease.
MeSH term(s)	Humans ; Female ; Receptors, Estrogen/genetics ; Receptors, Estrogen/metabolism ; Androgens/metabolism ; Lacrimal Apparatus/metabolism ; Estrogen Receptor alpha/genetics ; Estrogen Receptor alpha/metabolism ; Estrogen Receptor beta/metabolism ; Receptors, Androgen/genetics ; Receptors, Androgen/metabolism ; Gonadal Steroid Hormones/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	Receptors, Estrogen ; Androgens ; Estrogen Receptor alpha ; Estrogen Receptor beta ; Receptors, Androgen ; Gonadal Steroid Hormones ; RNA, Messenger
Language	English
Publishing date	2023-03-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24065609
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Article ; Online: Lipidomic analysis links mycobactin synthase K to iron uptake and virulence in M. tuberculosis.

Cressida A Madigan / Amanda Jezek Martinot / Jun-Rong Wei / Ashoka Madduri / Tan-Yun Cheng / David C Young / Emilie Layre / Jeffrey P Murry / Eric J Rubin / D Branch Moody

PLoS Pathogens, Vol 11, Iss 3, p e

2015 Volume 1004792

Abstract	The prolonged survival of Mycobacterium tuberculosis (M. tb) in the host fundamentally depends on scavenging essential nutrients from host sources. M. tb scavenges non-heme iron using mycobactin and carboxymycobactin siderophores, synthesized by mycobactin synthases (Mbt). Although a general mechanism for mycobactin biosynthesis has been proposed, the biological functions of individual mbt genes remain largely untested. Through targeted gene deletion and global lipidomic profiling of intact bacteria, we identify the essential biochemical functions of two mycobactin synthases, MbtK and MbtN, in siderophore biosynthesis and their effects on bacterial growth in vitro and in vivo. The deletion mutant, ΔmbtN, produces only saturated mycobactin and carboxymycobactin, demonstrating an essential function of MbtN as the mycobactin dehydrogenase, which affects antigenicity but not iron uptake or M. tb growth. In contrast, deletion of mbtK ablated all known forms of mycobactin and its deoxy precursors, defining MbtK as the essential acyl transferase. The mbtK mutant showed markedly reduced iron scavenging and growth in vitro. Further, ΔmbtK was attenuated for growth in mice, demonstrating a non-redundant role of hydroxamate siderophores in virulence, even when other M. tb iron scavenging mechanisms are operative. The unbiased lipidomic approach also revealed unexpected consequences of perturbing mycobactin biosynthesis, including extreme depletion of mycobacterial phospholipids. Thus, lipidomic profiling highlights connections among iron acquisition, phospholipid homeostasis, and virulence, and identifies MbtK as a lynchpin at the crossroads of these phenotypes.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2015-03-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: The Effect of High-Pressure Processing on the Survival of Non-O157 Shiga Toxin-Producing

Kameník, Josef / Dušková, Marta / Dorotíková, Kateřina / Hušáková, Markéta / Ježek, František

Microorganisms

2023 Volume 11, Issue 2

Abstract: Samples of steak tartare were artificially contaminated with a cocktail of Shiga toxin- ... ...

Abstract	Samples of steak tartare were artificially contaminated with a cocktail of Shiga toxin-producing
Language	English
Publishing date	2023-02-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11020377
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Article ; Online: Pathohistological features of the aging human lacrimal gland.

Hat, Koraljka / Kaštelan, Snježana / Planinić, Ana / Muller, Danko / Ježek, Davor

Croatian medical journal

2023 Volume 64, Issue 5, Page(s) 307–319

Abstract: Aim: To assess sex-related differences in the pathohistological features of the human lacrimal gland and to investigate age-related and sex-related differences in stereologically measured volume density of the secretory tissue, connective tissue, and ... ...

Abstract	Aim: To assess sex-related differences in the pathohistological features of the human lacrimal gland and to investigate age-related and sex-related differences in stereologically measured volume density of the secretory tissue, connective tissue, and fat. Methods: We performed an observational analysis of acinar atrophy, periacinar fibrosis, periductal fibrosis, ductal dilation, ductal proliferation, fatty infiltration, and lymphocyte infiltration of hematoxylin and eosin-stained lacrimal gland samples from 81 cornea donors. Stereological analysis of the volume density of the secretory tissue, connective tissue, and fat was performed on samples from 66 donors. Results: Up to 69% of all samples showed degenerative changes. Female samples had a higher frequency of all observed degenerative changes, except ductal dilation. While acinar atrophy was significantly more prevalent in women, ductal dilation was significantly more prevalent in men. Stereological analysis indicated lower portions of acini and higher portions of connective tissue and fat, as well as a more pronounced age-related progression of degenerative changes in female samples. Conclusion: Female lacrimal glands are more susceptible to degeneration, and this susceptibility could play an important role in the higher incidence of dry eye disease in older women. A further stereological analysis using more samples from younger age groups is needed to elucidate age-related and sex-related differences in the structure of the human lacrimal gland and their impact on dry eye disease.
MeSH term(s)	Aged ; Female ; Humans ; Male ; Aging ; Atrophy/complications ; Atrophy/pathology ; Dry Eye Syndromes/epidemiology ; Dry Eye Syndromes/etiology ; Dry Eye Syndromes/pathology ; Fibrosis ; Lacrimal Apparatus/pathology
Language	English
Publishing date	2023-11-04
Publishing country	Croatia
Document type	Journal Article ; Observational Study
ZDB-ID	1157623-6
ISSN	1332-8166 ; 0353-9504
ISSN (online)	1332-8166
ISSN	0353-9504
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Article ; Online: Time Spent on Daily Activities and Its Association with Life Satisfaction among Czech Adolescents from 1992 to 2019.

Kvasková, Lucia / Rečka, Karel / Ježek, Stanislav / Macek, Petr

International journal of environmental research and public health

2022 Volume 19, Issue 15

Abstract: Life satisfaction, an important precursor of adolescents' well-being, is linked to daily activities. Substantial changes have been noted in adolescents' daily activities over the years, raising the question of possible consequences for life satisfaction. ...

Abstract	Life satisfaction, an important precursor of adolescents' well-being, is linked to daily activities. Substantial changes have been noted in adolescents' daily activities over the years, raising the question of possible consequences for life satisfaction. This study aimed to explore changes in adolescents' life satisfaction and their time spent on daily activities (sleeping, engaging in sports, online gaming, school commuting, time spent at school) and further investigate the associations between adolescents' life satisfaction and these daily activities. The sample comprised 2715 adolescents from birth cohorts surveyed at four time points between 1992 and 2019. Participants were administered the Daily Activities Inventory and the Berne Questionnaire on Adolescents' Well-Being. Robust ANOVA with post hoc tests and spline regression were employed. We found cohort differences in sleep duration (8.6 h a day on average in 1992 and 7.5 in 2019). Sleep duration of 8 h and 1 h of sports activities had a beneficial effect on life satisfaction, while more than 1 h of online gaming had a negative impact. Neither school attendance nor commuting to school was associated with adolescents' life satisfaction. The results of this study can inform public-health policies to promote sleeping and sports habits in adolescence.
MeSH term(s)	Adolescent ; Czech Republic ; Humans ; Personal Satisfaction ; Schools ; Sleep ; Surveys and Questionnaires
Language	English
Publishing date	2022-08-01
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2175195-X
ISSN	1660-4601 ; 1661-7827
ISSN (online)	1660-4601
ISSN	1661-7827
DOI	10.3390/ijerph19159422
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Book ; Online: Ethereum Data Structures

Jezek, Kamil

2021

Abstract: Ethereum platform operates with rich spectrum of data structures and hashing and coding functions. The main source describing them is the Yellow paper, complemented by a lot of informal blogs. These sources are somehow limited. In particular, the Yellow ... ...

Abstract	Ethereum platform operates with rich spectrum of data structures and hashing and coding functions. The main source describing them is the Yellow paper, complemented by a lot of informal blogs. These sources are somehow limited. In particular, the Yellow paper does not ideally balance brevity and detail, in some parts it is very detail, while too shallow elsewhere. The blogs on the other hand are often too vague and in certain cases contain incorrect information. As a solution, we provide this document, which summarises data structures used in Ethereum. The goal is to provide sufficient detail while keeping brevity. Sufficiently detailed formal view is enriched with examples to extend on clarity.
Keywords	Computer Science - Computation and Language
Publishing date	2021-08-11
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: BCAA metabolism in pancreatic cancer affects lipid balance by regulating fatty acid import into mitochondria.

Gotvaldová, Klára / Špačková, Jitka / Novotný, Jiří / Baslarová, Kamila / Ježek, Petr / Rossmeislová, Lenka / Gojda, Jan / Smolková, Katarína

Cancer & metabolism

2024 Volume 12, Issue 1, Page(s) 10

Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC) has been associated with the host dysmetabolism of branched-chain amino acids (BCAAs), however, the implications for the role of BCAA metabolism in PDAC development or progression are not clear. The ... ...

Abstract	Background: Pancreatic ductal adenocarcinoma (PDAC) has been associated with the host dysmetabolism of branched-chain amino acids (BCAAs), however, the implications for the role of BCAA metabolism in PDAC development or progression are not clear. The mitochondrial catabolism of valine, leucine, and isoleucine is a multistep process leading to the production of short-chain R-CoA species. They can be subsequently exported from mitochondria as short-chain carnitines (SC-CARs), utilized in anabolic pathways, or released from the cells. Methods: We examined the specificities of BCAA catabolism and cellular adaptation strategies to BCAA starvation in PDAC cells in vitro. We used metabolomics and lipidomics to quantify major metabolic changes in response to BCAA withdrawal. Using confocal microscopy and flow cytometry we quantified the fluorescence of BODIPY probe and the level of lipid droplets (LDs). We used BODIPY-conjugated palmitate to evaluate transport of fatty acids (FAs) into mitochondria. Also, we have developed a protocol for quantification of SC-CARs, BCAA-derived metabolites. Results: Using metabolic profiling, we found that BCAA starvation leads to massive triglyceride (TG) synthesis and LD accumulation. This was associated with the suppression of activated FA transport into the mitochondrial matrix. The suppression of FA import into mitochondria was rescued with the inhibitor of the acetyl-CoA carboxylase (ACC) and the activator of AMP kinase (AMPK), which both regulate carnitine palmitoyltransferase 1A (CPT1) activation status. Conclusions: Our data suggest that BCAA catabolism is required for the import of long chain carnitines (LC-CARs) into mitochondria, whereas the disruption of this link results in the redirection of activated FAs into TG synthesis and its deposition into LDs. We propose that this mechanism protects cells against mitochondrial overload with LC-CARs and it might be part of the universal reaction to amino acid perturbations during cancer growth, regulating FA handling and storage.
Language	English
Publishing date	2024-03-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2700141-6
ISSN	2049-3002
ISSN	2049-3002
DOI	10.1186/s40170-024-00335-5
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Article ; Online: Non-blocking programmable delay line with minimal dead time and tens of picoseconds jitter.

Mazin, Glib / Stejskal, Aleš / Dudka, Michal / Ježek, Miroslav

The Review of scientific instruments

2021 Volume 92, Issue 11, Page(s) 114712

Abstract: ... on the temperature with the slope of 0.2 ps K ...

Abstract	We report a non-blocking high-resolution digital delay line based on an asynchronous circuit design. Field-programmable gate array logic primitives were used as a source of delay and optimally arranged using combinatorial optimization. This approach allows for an efficient trade-off of the resolution and a delay range together with a minimized dead time operation. We demonstrate the method by implementing the delay line adjustable from 23 ns up to 1635 ns with a resolution of 10 ps. We present a detailed experimental characterization of the device focusing on thermal instability, timing jitter, and pulse spreading, which represent three main issues of the asynchronous design. We found a linear dependence of the delay on the temperature with the slope of 0.2 ps K
Language	English
Publishing date	2021-12-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	209865-9
ISSN	1089-7623 ; 0034-6748
ISSN (online)	1089-7623
ISSN	0034-6748
DOI	10.1063/5.0056828
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