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Article ; Online: Amino acid availability acts as a metabolic rheostat to determine the magnitude of ILC2 responses.

Hodge, Suzanne H / Krauss, Maria Z / Kaymak, Irem / King, James I / Howden, Andrew J M / Panic, Gordana / Grencis, Richard K / Swann, Jonathan R / Sinclair, Linda V / Hepworth, Matthew R

The Journal of experimental medicine

2022 Volume 220, Issue 3

Abstract: Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the ... ...

Abstract	Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens-including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 are found to be uniquely preprimed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine-producing capacity of ILC2. Mechanistically, amino acid uptake determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues.
MeSH term(s)	Immunity, Innate ; Lymphocytes/metabolism ; Amino Acids/metabolism ; Cytokines/metabolism ; Mucous Membrane/metabolism
Chemical Substances	Amino Acids ; Cytokines
Language	English
Publishing date	2022-12-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20221073
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Article: Genes for anti-Müllerian hormone and androgen receptor are underexpressed in human cumulus cells surrounding morphologically highly graded oocytes.

Dević Pavlić, Sanja / Tramišak Milaković, Tamara / Panić Horvat, Linda / Čavlović, Kristina / Vlašić, Hrvoje / Manestar, Miljenko / Smiljan Severinski, Neda / Radojčić Badovinac, Anđelka

SAGE open medicine

2019 Volume 7, Page(s) 2050312119865137

Abstract: Objectives: The aim of this study was to investigate the expression of genes crucial for the quality of the oocyte and whether expression levels of these genes in cumulus cells can be biological markers for the quality of the oocyte, zygote or embryo, ... ...

Abstract	Objectives: The aim of this study was to investigate the expression of genes crucial for the quality of the oocyte and whether expression levels of these genes in cumulus cells can be biological markers for the quality of the oocyte, zygote or embryo, or even for achievement of pregnancy after the assisted reproductive technology procedure. We examined the expression profile of the anti-Müllerian hormone (AMH) gene and its respective receptors: anti-Müllerian hormone receptor type 2 (AMHR2), follicle-stimulating hormone receptor (FSHR) and androgen receptor (AR) in cumulus cells (CCs) surrounding the oocyte, as well as AMH concentrations in follicular fluid of the associated follicle. The obtained gene expression levels were correlated with the morphological quality of the associated oocyte, zygote and embryo as well as with assisted reproductive technology outcome following the intracytoplasmic sperm injection procedure. Methods: This study involved 129 cumulus cells and 35 follicular fluid samples, taken from 58 patients undergoing the intracytoplasmic sperm injection procedure. Oocytes, zygotes and embryos were assessed for morphological quality. The relative gene expression of AMH, AMHR2, FSHR and AR was calculated using the delta-delta Ct method. Anti-Müllerian hormone concentrations in follicular fluids were measured by enzyme-linked immunosorbent assay. Results: The results yielded suggest a relationship between AMH, AR and oocyte morphology: AMH and AR gene expression levels in CCs surrounding morphologically optimal oocytes were significantly lower than in CCs surrounding oocytes with suboptimal morphology (p = 0.011 and p = 0.008, respectively). Statistically significant positive correlation was found between mRNA expression levels of AMH and FSHR (p < 0.001), AMH and AR (p = 0.001), AMHR2 and FSHR (p < 0.001), AMHR2 and AR (p < 0.001), as well as between FSHR and AR (p < 0.001). Conclusion: Assessed results point to AMH and AR relation with oocyte maturity, but not with its fertilization potential, or with embryo quality.
Language	English
Publishing date	2019-07-16
Publishing country	England
Document type	Journal Article
ZDB-ID	2735399-0
ISSN	2050-3121
ISSN	2050-3121
DOI	10.1177/2050312119865137
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Article ; Online: Exploring the link between star and planet formation with Ariel.

Turrini, Diego / Codella, Claudio / Danielski, Camilla / Fedele, Davide / Fonte, Sergio / Garufi, Antonio / Guarcello, Mario Giuseppe / Helled, Ravit / Ikoma, Masahiro / Kama, Mihkel / Kimura, Tadahiro / Kruijssen, J M Diederik / Maldonado, Jesus / Miguel, Yamila / Molinari, Sergio / Nikolaou, Athanasia / Oliva, Fabrizio / Panić, Olja / Pignatari, Marco /

Podio, Linda / Rickman, Hans / Schisano, Eugenio / Shibata, Sho / Vazan, Allona / Wolkenberg, Paulina

Experimental astronomy

2021 Volume 53, Issue 2, Page(s) 225–278

Abstract: The goal of the Ariel space mission is to observe a large and diversified population of transiting planets around a range of host star types to collect information on their atmospheric composition. The planetary bulk and atmospheric compositions bear the ...

Abstract	The goal of the Ariel space mission is to observe a large and diversified population of transiting planets around a range of host star types to collect information on their atmospheric composition. The planetary bulk and atmospheric compositions bear the marks of the way the planets formed: Ariel's observations will therefore provide an unprecedented wealth of data to advance our understanding of planet formation in our Galaxy. A number of environmental and evolutionary factors, however, can affect the final atmospheric composition. Here we provide a concise overview of which factors and effects of the star and planet formation processes can shape the atmospheric compositions that will be observed by Ariel, and highlight how Ariel's characteristics make this mission optimally suited to address this very complex problem.
Language	English
Publishing date	2021-10-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2012330-9
ISSN	1572-9508 ; 0922-6435
ISSN (online)	1572-9508
ISSN	0922-6435
DOI	10.1007/s10686-021-09754-4
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Article ; Online: S6-haploinsufficiency activates the p53 tumor suppressor.

Panić, Linda / Montagne, Jacques / Cokarić, Maja / Volarević, Sinisa

Cell cycle (Georgetown, Tex.)

2007 Volume 6, Issue 1, Page(s) 20–24

Abstract: The capacity to detect and appropriately respond to many different stresses that interfere with functional homeostasis is essential for survival. Recent evidence suggests that the nucleolus, the site of ribosome biogenesis, plays a critical role in ... ...

Abstract	The capacity to detect and appropriately respond to many different stresses that interfere with functional homeostasis is essential for survival. Recent evidence suggests that the nucleolus, the site of ribosome biogenesis, plays a critical role in sensing and responding to both external and internal stresses. To understand these processes, we have recently used a genetically defined in vivo mouse model in which ribosome biogenesis could be manipulated during oogenesis and embryo development. In these mice ribosomal biosynthesis is impaired by a conditional deletion of one allele of the gene encoding 40S ribosomal protein S6. Embryos from these animals fail during gastrulation, apparently due to a p53-dependent checkpoint being triggered, rather than a deficit in translational capacity. These findings imply that molecular mechanisms have evolved during mammalian evolution to strongly guard against potential heterozygosity for ribosomal protein genes.
MeSH term(s)	Animals ; Gene Dosage/physiology ; Gene Expression Regulation ; Haplotypes/physiology ; Humans ; Mice ; Ribosomal Protein S6/deficiency ; Ribosomal Protein S6/genetics ; Ribosomal Protein S6/physiology ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Ribosomal Protein S6 ; Tumor Suppressor Protein p53 ; ribosomal protein S6, mouse
Language	English
Publishing date	2007-01-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2146183-1
ISSN	1551-4005 ; 1538-4101 ; 1554-8627
ISSN (online)	1551-4005
ISSN	1538-4101 ; 1554-8627
DOI	10.4161/cc.6.1.3666
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Article ; Online: Follicular fluid anti-Müllerian hormone: a predictive marker of fertilization capacity of MII oocytes.

Tramišak Milaković, Tamara / Panić Horvat, Linda / Čavlović, Kristina / Smiljan Severinski, Neda / Vlašić, Hrvoje / Vlastelić, Ivan / Ljiljak, Dejan / Radojčić Badovinac, Anđelka

Archives of gynecology and obstetrics

2015 Volume 291, Issue 3, Page(s) 681–687

Abstract: Purpose: The present study aimed to correlate anti-Müllerian hormone (AMH) levels in follicular fluid (FF) with oocyte maturity stages, morphological quality of metaphase II (MII) oocyte and fertilization capacity of MII oocytes.: Methods: A total of ...

Abstract	Purpose: The present study aimed to correlate anti-Müllerian hormone (AMH) levels in follicular fluid (FF) with oocyte maturity stages, morphological quality of metaphase II (MII) oocyte and fertilization capacity of MII oocytes. Methods: A total of 92 infertile women undergoing controlled ovarian stimulation and intracytoplasmic sperm injection were analyzed. Patients were divided into two groups according to age: <35 years (n = 43) and ≥35 years (n = 49). An FF sample was obtained from a single dominant follicle in each patient for a total of 92 follicular fluid samples analyzed. AMH levels in serum and follicular fluid were measured by enzyme-linked immunosorbent assay. Mature MII oocytes, zygotes, and embryos were assessed for morphological quality. Results: Serum AMH levels were significantly higher in patients aged <35 years. No correlation was observed between FF AMH level and oocyte maturation stages or morphological quality of MII oocyte. Significantly lower FF AMH levels were observed in fertilized MII oocytes than in non-fertilized MII oocytes in patients aged <35 years (2.56 ± 2.0 ng/ml vs. 4.81 ± 4.14 ng/ml; p = 0.032). Conclusions: The present study revealed no correlation between FF AMH and oocyte maturity stage or morphological quality of MII oocyte. However, FF AMH might be a predictive marker for fertilization capacity of MII oocytes.
MeSH term(s)	Adult ; Age Factors ; Anti-Mullerian Hormone/analysis ; Anti-Mullerian Hormone/metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Fertilization in Vitro ; Follicular Fluid/chemistry ; Follicular Fluid/metabolism ; Humans ; Infertility, Female/therapy ; Metaphase ; Oocytes/cytology ; Oocytes/physiology ; Oogenesis ; Ovarian Follicle/metabolism ; Ovulation Induction ; Predictive Value of Tests ; Pregnancy ; Pregnancy Rate ; Sperm Injections, Intracytoplasmic
Chemical Substances	Anti-Mullerian Hormone (80497-65-0)
Language	English
Publishing date	2015-03
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	896455-5
ISSN	1432-0711 ; 0932-0067
ISSN (online)	1432-0711
ISSN	0932-0067
DOI	10.1007/s00404-014-3460-9
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Article ; Online: Genes for anti-Müllerian hormone and androgen receptor are underexpressed in human cumulus cells surrounding morphologically highly graded oocytes

Sanja Dević Pavlić / Tamara Tramišak Milaković / Linda Panić Horvat / Kristina Čavlović / Hrvoje Vlašić / Miljenko Manestar / Neda Smiljan Severinski / Anđelka Radojčić Badovinac

SAGE Open Medicine, Vol

2019 Volume 7

Abstract	Objectives: The aim of this study was to investigate the expression of genes crucial for the quality of the oocyte and whether expression levels of these genes in cumulus cells can be biological markers for the quality of the oocyte, zygote or embryo, or even for achievement of pregnancy after the assisted reproductive technology procedure. We examined the expression profile of the anti-Müllerian hormone (AMH) gene and its respective receptors: anti-Müllerian hormone receptor type 2 (AMHR2), follicle-stimulating hormone receptor (FSHR) and androgen receptor (AR) in cumulus cells (CCs) surrounding the oocyte, as well as AMH concentrations in follicular fluid of the associated follicle. The obtained gene expression levels were correlated with the morphological quality of the associated oocyte, zygote and embryo as well as with assisted reproductive technology outcome following the intracytoplasmic sperm injection procedure. Methods: This study involved 129 cumulus cells and 35 follicular fluid samples, taken from 58 patients undergoing the intracytoplasmic sperm injection procedure. Oocytes, zygotes and embryos were assessed for morphological quality. The relative gene expression of AMH, AMHR2, FSHR and AR was calculated using the delta–delta Ct method. Anti-Müllerian hormone concentrations in follicular fluids were measured by enzyme-linked immunosorbent assay. Results: The results yielded suggest a relationship between AMH, AR and oocyte morphology: AMH and AR gene expression levels in CCs surrounding morphologically optimal oocytes were significantly lower than in CCs surrounding oocytes with suboptimal morphology (p = 0.011 and p = 0.008, respectively). Statistically significant positive correlation was found between mRNA expression levels of AMH and FSHR (p < 0.001), AMH and AR (p = 0.001), AMHR2 and FSHR (p < 0.001), AMHR2 and AR (p < 0.001), as well as between FSHR and AR (p < 0.001). Conclusion: Assessed results point to AMH and AR relation with oocyte maturity, but not with its fertilization ...
Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	SAGE Publishing
Document type	Article ; Online
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Article: Deregulation of cell growth and malignant transformation.

Sulić, Sanda / Panić, Linda / Dikić, Ivan / Volarević, Sinisa

Croatian medical journal

2005 Volume 46, Issue 4, Page(s) 622–638

Abstract: Cell growth and cell division are fundamental aspects of cell behavior in all organisms. Recent insights from many model organisms have shed light on the molecular mechanisms that control cell growth and cell division. A significant body of evidence has ... ...

Abstract	Cell growth and cell division are fundamental aspects of cell behavior in all organisms. Recent insights from many model organisms have shed light on the molecular mechanisms that control cell growth and cell division. A significant body of evidence has now been accumulated, showing a direct link between deregulation of components of cell cycle machinery and cancer. In addition, defects in one or more steps that control growth are important for malignant transformation, as many tumor suppressors and proto-oncogenes have been found to regulate cell growth. The importance of cell growth in tumor development is further supported by the discovery that rapamycin, an effective anticancer drug, inhibits a key regulator of protein synthetic machinery and cell growth, mammalian target of rapamycin (mTOR). In most cases, cell growth and cell division are coupled, thereby maintaining cell size within physiological limits. We believe that, in a long-term perspective, understanding how these two processes are coordinated in vivo and how their interplay is deregulated in a number of diseases, including cancer, may have a direct impact on the efficiency of modern therapeutics.
MeSH term(s)	Cell Division ; Cell Transformation, Neoplastic ; Germany ; Humans ; Neoplasms/etiology ; Neoplasms/pathology
Language	English
Publishing date	2005-08
Publishing country	Croatia
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1157623-6
ISSN	1332-8166 ; 0353-9504
ISSN (online)	1332-8166
ISSN	0353-9504
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Article ; Online: The p53 tumor suppressor causes congenital malformations in Rpl24-deficient mice and promotes their survival.

Barkić, Martina / Crnomarković, Sladana / Grabusić, Kristina / Bogetić, Ivana / Panić, Linda / Tamarut, Sanda / Cokarić, Maja / Jerić, Ines / Vidak, Sandra / Volarević, Sinisa

Molecular and cellular biology

2009 Volume 29, Issue 10, Page(s) 2489–2504

Abstract: Hypomorphic mutation in one allele of ribosomal protein l24 gene (Rpl24) is responsible for the Belly Spot and Tail (Bst) mouse, which suffers from defects of the eye, skeleton, and coat pigmentation. It has been hypothesized that these pathological ... ...

Abstract	Hypomorphic mutation in one allele of ribosomal protein l24 gene (Rpl24) is responsible for the Belly Spot and Tail (Bst) mouse, which suffers from defects of the eye, skeleton, and coat pigmentation. It has been hypothesized that these pathological manifestations result exclusively from faulty protein synthesis. We demonstrate here that upregulation of the p53 tumor suppressor during the restricted period of embryonic development significantly contributes to the Bst phenotype. However, in the absence of p53 a large majority of Rpl24(Bst/+) embryos die. We showed that p53 promotes survival of these mice via p21-dependent mechanism. Our results imply that activation of a p53-dependent checkpoint mechanism in response to various ribosomal protein deficiencies might also play a role in the pathogenesis of congenital malformations in humans.
MeSH term(s)	Animals ; Apoptosis/physiology ; Cyclin-Dependent Kinase Inhibitor p21/genetics ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Embryo, Mammalian/anatomy & histology ; Embryo, Mammalian/physiology ; Eye Abnormalities/genetics ; Female ; Gene Expression Regulation, Developmental ; Hair Color/genetics ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Musculoskeletal Abnormalities/genetics ; Phenotype ; Pregnancy ; RNA Interference ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Ribosomal Proteins/genetics ; Ribosomal Proteins/metabolism ; Survival Rate ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Cyclin-Dependent Kinase Inhibitor p21 ; RNA, Small Interfering ; Ribosomal Proteins ; Tumor Suppressor Protein p53 ; ribosomal protein L24
Language	English
Publishing date	2009-03-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.01588-08
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Article: Ribosomal protein S6 gene haploinsufficiency is associated with activation of a p53-dependent checkpoint during gastrulation.

Panić, Linda / Tamarut, Sanda / Sticker-Jantscheff, Melanie / Barkić, Martina / Solter, Davor / Uzelac, Miljana / Grabusić, Kristina / Volarević, Sinisa

Molecular and cellular biology

2006 Volume 26, Issue 23, Page(s) 8880–8891

Abstract: Nascent ribosome biogenesis is required during cell growth. To gain insight into the importance of this process during mouse oogenesis and embryonic development, we deleted one allele of the ribosomal protein S6 gene in growing oocytes and generated S6- ... ...

Abstract	Nascent ribosome biogenesis is required during cell growth. To gain insight into the importance of this process during mouse oogenesis and embryonic development, we deleted one allele of the ribosomal protein S6 gene in growing oocytes and generated S6-heterozygous embryos. Oogenesis and embryonic development until embryonic day 5.5 (E5.5) were normal. However, inhibition of entry into M phase of the cell cycle and apoptosis became evident post-E5.5 and led to perigastrulation lethality. Genetic inactivation of p53 bypassed this checkpoint and prolonged development until E12.5, when the embryos died, showing decreased expression of D-type cyclins, diminished fetal liver erythropoiesis, and placental defects. Thus, a p53-dependent checkpoint is activated during gastrulation in response to ribosome insufficiency to prevent improper execution of the developmental program.
MeSH term(s)	Animals ; Blastocyst/cytology ; Cell Cycle/genetics ; Cell Cycle/physiology ; Cells, Cultured ; Female ; Gastrula/physiology ; Immunohistochemistry ; Mice ; Mice, Knockout ; Pregnancy ; Ribosomal Protein S6/genetics ; Ribosomal Protein S6/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Ribosomal Protein S6 ; Tumor Suppressor Protein p53 ; ribosomal protein S6, mouse
Language	English
Publishing date	2006-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	779397-2
ISSN	1098-5549 ; 0270-7306
ISSN (online)	1098-5549
ISSN	0270-7306
DOI	10.1128/MCB.00751-06
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Article: Inactivation of S6 ribosomal protein gene in T lymphocytes activates a p53-dependent checkpoint response.

Sulic, Sanda / Panic, Linda / Barkic, Martina / Mercep, Mladen / Uzelac, Miljana / Volarevic, Sinisa

Genes & development

2005 Volume 19, Issue 24, Page(s) 3070–3082

Abstract: Ribosome biogenesis has been associated with regulation of cell growth and cell division, but the molecular mechanisms that integrate the effect of ribosome biogenesis on these processes in mammalian cells remain unknown. To study the effect of impaired ... ...

Abstract	Ribosome biogenesis has been associated with regulation of cell growth and cell division, but the molecular mechanisms that integrate the effect of ribosome biogenesis on these processes in mammalian cells remain unknown. To study the effect of impaired ribosome functions in vivo, we conditionally deleted one or two alleles of the 40S ribosomal protein S6 gene in T cells in the mouse. While complete deletion of S6 abrogated T-cell development, hemizygous expression did not have any effect on T-cell maturation in the thymus, but inhibited the accumulation of T cells in the spleen and lymph nodes, as a result of their decreased survival in the peripheral lymphoid organs. Additionally, TCR-mediated stimulation of S6-heterozygous T cells induced a normal increase in their size, but cell cycle progression was impaired. Genetic inactivation of p53 tumor suppressor rescued development of S6-homozygous null thymocytes and proliferative defect of S6-heterozygous T cells. These results demonstrate the existence of a p53-dependent checkpoint mechanism that senses changes in the fidelity of the translational machinery to prevent aberrant cell division or eliminate defective T cells in vivo. Failure to activate this checkpoint response could potentially lead to a development of pathological processes such as tumors and autoimmune diseases.
MeSH term(s)	Animals ; Autoimmune Diseases/genetics ; Autoimmune Diseases/metabolism ; Cell Cycle ; Cell Differentiation ; Lymphocyte Activation ; Lymphoid Tissue/cytology ; Lymphoid Tissue/metabolism ; Mice ; Mice, Transgenic ; Neoplasms/genetics ; Neoplasms/metabolism ; Protein Biosynthesis ; Receptors, Antigen, T-Cell/metabolism ; Ribosomal Protein S6/genetics ; Ribosomal Protein S6/metabolism ; Ribosomes/metabolism ; T-Lymphocytes/cytology ; T-Lymphocytes/metabolism ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Receptors, Antigen, T-Cell ; Ribosomal Protein S6 ; Tumor Suppressor Protein p53
Language	English
Publishing date	2005-12-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	806684-x
ISSN	1549-5477 ; 0890-9369
ISSN (online)	1549-5477
ISSN	0890-9369
DOI	10.1101/gad.359305
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