TY  - CONF
AU  - Danilović Luković, Jelena
AU  - Radovanovic, Anita
AU  - Milošević, Ivan
AU  - Lužajić, Tijana
AU  - Milanović, Svetlana
AU  - Kovačević Filipović, Milica
AU  - Korać, Aleksandra
PY  - 2018
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2698
AB  - The stimulative effects of thyroid hormones on mitochondria are realized through both non-genomic and genomic mechanisms, affecting respiration, mitochondrial plasticity and biogenesis. The subclinical form of maternal hypothyroidism in rats induces significant reduction of mitochondria number but also an augmentation of their area in neonatal and early infantile offspring dyctiotene oocytes. This study aimed to investigate if this form of subclinical hypothyroidism affects mitochondrial morphology and distribution in the early prophase of meiosis I oocytes. It was performed on newborn control (C) (n=10) and hypothyroid (SCH) (n=10) female rat pups derived from control (n=6) and propylthiouracil treated pregnant dams (n=6), respectively. Ovaries of all pups were removed and processed for transmission electron microscopy. The morphological features of mitochondria in the early prophase I oocytes until dyctiotene were assessed. No substantial differences were found in leptotene and zygotene oocytes in SCH group comparing to control, except just a few mitochondria characterized with shortened cristae, presence of wide pale area centrally positioned and membrane disruption. Pachytene mitochondria in treated pup oocytes were in great extent with disrupted membrane, shortened cristae and wide pale area centrally positioned while these features were rarely observed in control ones. Our results confirm altered mitochondria morphology found in primordial and primary follicles in case of maternal hypothyroidism, indicating their impaired function and possibly, propensity to programmed cell death. Further investigations may indicate to what extent pachytene, as a meiotic checkpoint, appears to be a milestone possibly predetermining the future of the cell.
PB  - Serbian Society for Mitochondrial and Free Radical Physiology Ministry of Education, Science and Technological Development University of Belgrade Faculty of Biology of University of Belgrade
C3  - Fourth Congress "Challenges in redox biology", September 28-30. 2018, Belgrade
T1  - Mitochondria in pachytene: the fragile point of maternal subclinical hypothyroidism affection
EP  - 57
SP  - 57
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2698
ER  - 

@conference{
author = "Danilović Luković, Jelena and Radovanovic, Anita and Milošević, Ivan and Lužajić, Tijana and Milanović, Svetlana and Kovačević Filipović, Milica and Korać, Aleksandra",
year = "2018",
abstract = "The stimulative effects of thyroid hormones on mitochondria are realized through both non-genomic and genomic mechanisms, affecting respiration, mitochondrial plasticity and biogenesis. The subclinical form of maternal hypothyroidism in rats induces significant reduction of mitochondria number but also an augmentation of their area in neonatal and early infantile offspring dyctiotene oocytes. This study aimed to investigate if this form of subclinical hypothyroidism affects mitochondrial morphology and distribution in the early prophase of meiosis I oocytes. It was performed on newborn control (C) (n=10) and hypothyroid (SCH) (n=10) female rat pups derived from control (n=6) and propylthiouracil treated pregnant dams (n=6), respectively. Ovaries of all pups were removed and processed for transmission electron microscopy. The morphological features of mitochondria in the early prophase I oocytes until dyctiotene were assessed. No substantial differences were found in leptotene and zygotene oocytes in SCH group comparing to control, except just a few mitochondria characterized with shortened cristae, presence of wide pale area centrally positioned and membrane disruption. Pachytene mitochondria in treated pup oocytes were in great extent with disrupted membrane, shortened cristae and wide pale area centrally positioned while these features were rarely observed in control ones. Our results confirm altered mitochondria morphology found in primordial and primary follicles in case of maternal hypothyroidism, indicating their impaired function and possibly, propensity to programmed cell death. Further investigations may indicate to what extent pachytene, as a meiotic checkpoint, appears to be a milestone possibly predetermining the future of the cell.",
publisher = "Serbian Society for Mitochondrial and Free Radical Physiology Ministry of Education, Science and Technological Development University of Belgrade Faculty of Biology of University of Belgrade",
journal = "Fourth Congress "Challenges in redox biology", September 28-30. 2018, Belgrade",
title = "Mitochondria in pachytene: the fragile point of maternal subclinical hypothyroidism affection",
pages = "57-57",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2698"
}

Danilović Luković, J., Radovanovic, A., Milošević, I., Lužajić, T., Milanović, S., Kovačević Filipović, M.,& Korać, A.. (2018). Mitochondria in pachytene: the fragile point of maternal subclinical hypothyroidism affection. in Fourth Congress "Challenges in redox biology", September 28-30. 2018, Belgrade
Serbian Society for Mitochondrial and Free Radical Physiology Ministry of Education, Science and Technological Development University of Belgrade Faculty of Biology of University of Belgrade., 57-57.
https://hdl.handle.net/21.15107/rcub_rimsi_2698

Danilović Luković J, Radovanovic A, Milošević I, Lužajić T, Milanović S, Kovačević Filipović M, Korać A. Mitochondria in pachytene: the fragile point of maternal subclinical hypothyroidism affection. in Fourth Congress "Challenges in redox biology", September 28-30. 2018, Belgrade. 2018;:57-57.
https://hdl.handle.net/21.15107/rcub_rimsi_2698 .

Danilović Luković, Jelena, Radovanovic, Anita, Milošević, Ivan, Lužajić, Tijana, Milanović, Svetlana, Kovačević Filipović, Milica, Korać, Aleksandra, "Mitochondria in pachytene: the fragile point of maternal subclinical hypothyroidism affection" in Fourth Congress "Challenges in redox biology", September 28-30. 2018, Belgrade (2018):57-57,
https://hdl.handle.net/21.15107/rcub_rimsi_2698 .

TY  - CONF
AU  - Danilović Luković, Jelena
AU  - Korać, Aleksandra
AU  - Milošević, Ivan
AU  - Lužajić, Tijana
AU  - Kovačević Filipović, Milica
AU  - Radovanovic, Anita
PY  - 2017
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2700
AB  - The ovarian surface epithelium (OSE) is a very dynamic part of the ovary, with an
important role in ovulation during the reproductive period. It represents a source of germ cells in
the fetal period but data regarding the role of the OSE in the postnatal period are contradictory.
Although the OSE has been the subject of research in the past few years, its ultrastructure
in newborn rats has not yet been studied. The aim of this study was to examine rat OSE
ultrastructure features in the first 24h hours after birth.
Six newborn rats were euthanized at 12h±2 hours after birth. Their ovaries were fixed in
4% glutaraldehyde, post-fixed in 1% osmium tetroxide, routinely dehydrated and embedded in
araldite. Semi-thin sections were stained with toluidine blue, and used to select areas of interest.
Ultra-thin sections of selected areas were mounted on copper grids and examined under a
Philips CM12 transmission electron microscope. Ultrastructural analysis revealed the presence
of a typically single-layered OSE with sporadic pseudostratified appearance, both consisting
of cuboidal and/or columnar cells. The OSE cells’ nuclei had irregularly dispersed chromatin,
and a central or apical location. From the surface of the OSE cells numerous microvilli and
cytoplasmic projections extended towards the peritoneal cavity. Continuous tunica albuginea
was not found, but occasionally groups of fibroblast-like cells were present, indicating the onset
of its formation. Numerous oogonia and oocytes were identified between OSE cells or up to
their basal part, suggesting that extrusion (the release of germ cells into the peritoneal cavity)
may be an important mode of germ cell elimination.
In the early postnatal period in rat ovaries massive death takes place of oogonia and
oocytes, mostly via apoptosis and autophagy. Further investigation might reveal the contribution
of extrusion as another form of germ cell elimination for both, maintaining and balancing their
number in the ovary, which is necessary for proper reproductive function.
PB  - Faculty of Veterinary Medicine, University of Zagreb, Croatia
C3  - 7th International Congress Veterinary science and proffesion, October 5th-7th 2017, Zagreb - Book of abstracts
T1  - Ovarian surface epithelium in newborn rats: germ cells warehouse
EP  - 153
SP  - 153
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2700
ER  - 

@conference{
author = "Danilović Luković, Jelena and Korać, Aleksandra and Milošević, Ivan and Lužajić, Tijana and Kovačević Filipović, Milica and Radovanovic, Anita",
year = "2017",
abstract = "The ovarian surface epithelium (OSE) is a very dynamic part of the ovary, with an
important role in ovulation during the reproductive period. It represents a source of germ cells in
the fetal period but data regarding the role of the OSE in the postnatal period are contradictory.
Although the OSE has been the subject of research in the past few years, its ultrastructure
in newborn rats has not yet been studied. The aim of this study was to examine rat OSE
ultrastructure features in the first 24h hours after birth.
Six newborn rats were euthanized at 12h±2 hours after birth. Their ovaries were fixed in
4% glutaraldehyde, post-fixed in 1% osmium tetroxide, routinely dehydrated and embedded in
araldite. Semi-thin sections were stained with toluidine blue, and used to select areas of interest.
Ultra-thin sections of selected areas were mounted on copper grids and examined under a
Philips CM12 transmission electron microscope. Ultrastructural analysis revealed the presence
of a typically single-layered OSE with sporadic pseudostratified appearance, both consisting
of cuboidal and/or columnar cells. The OSE cells’ nuclei had irregularly dispersed chromatin,
and a central or apical location. From the surface of the OSE cells numerous microvilli and
cytoplasmic projections extended towards the peritoneal cavity. Continuous tunica albuginea
was not found, but occasionally groups of fibroblast-like cells were present, indicating the onset
of its formation. Numerous oogonia and oocytes were identified between OSE cells or up to
their basal part, suggesting that extrusion (the release of germ cells into the peritoneal cavity)
may be an important mode of germ cell elimination.
In the early postnatal period in rat ovaries massive death takes place of oogonia and
oocytes, mostly via apoptosis and autophagy. Further investigation might reveal the contribution
of extrusion as another form of germ cell elimination for both, maintaining and balancing their
number in the ovary, which is necessary for proper reproductive function.",
publisher = "Faculty of Veterinary Medicine, University of Zagreb, Croatia",
journal = "7th International Congress Veterinary science and proffesion, October 5th-7th 2017, Zagreb - Book of abstracts",
title = "Ovarian surface epithelium in newborn rats: germ cells warehouse",
pages = "153-153",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2700"
}

Danilović Luković, J., Korać, A., Milošević, I., Lužajić, T., Kovačević Filipović, M.,& Radovanovic, A.. (2017). Ovarian surface epithelium in newborn rats: germ cells warehouse. in 7th International Congress Veterinary science and proffesion, October 5th-7th 2017, Zagreb - Book of abstracts
Faculty of Veterinary Medicine, University of Zagreb, Croatia., 153-153.
https://hdl.handle.net/21.15107/rcub_rimsi_2700

Danilović Luković J, Korać A, Milošević I, Lužajić T, Kovačević Filipović M, Radovanovic A. Ovarian surface epithelium in newborn rats: germ cells warehouse. in 7th International Congress Veterinary science and proffesion, October 5th-7th 2017, Zagreb - Book of abstracts. 2017;:153-153.
https://hdl.handle.net/21.15107/rcub_rimsi_2700 .

Danilović Luković, Jelena, Korać, Aleksandra, Milošević, Ivan, Lužajić, Tijana, Kovačević Filipović, Milica, Radovanovic, Anita, "Ovarian surface epithelium in newborn rats: germ cells warehouse" in 7th International Congress Veterinary science and proffesion, October 5th-7th 2017, Zagreb - Book of abstracts (2017):153-153,
https://hdl.handle.net/21.15107/rcub_rimsi_2700 .

TY  - CONF
AU  - Danilović Luković, Jelena
AU  - Lazarević, Anita
AU  - Bogdanović, Maja
AU  - Abadijeva, Desislava
AU  - Atansasova, Milena
AU  - Gennadiy, Boryaev
AU  - Kistanova, Elena
AU  - Korać, Aleksandra
PY  - 2017
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2604
AB  - The selenium (Se) is an essential microelement included in diet for reproductive swine female. It is known that Se has an important role in antioxidative defense and maintenance of ovarian tissue in pathological conditions (1) though the information how it could be involved in healthy reproduction of female is limited. The present work is aimed to study the effect of injective application of organic compound selenopyran on ultrastructure of antral follicles of the porcine’s ovary. The experiment was conducted with 18 gilts of Danube white breed, ages between 120 - 228 days, divided into two groups each consisting of 9 animals. The animals received equal basal diets without selenium additives (Se content was 15 mg per kg of forage). The experimental gilts (Se-treated) were injected intramuscularly with oil solution of selenopyran (9-phenyl-symmetrical octahydroselenoxanthene) once per month (0.1 mg Se/kg live weight). After euthanasia of animals, tissue from one ovary of each animal was fixed in 4% glutaraldehyde, post-fixed in 1% osmium tetroxide, routinely dehydrated and embedded in Durcupan. Semi-thin sections were stained with Toluidine blue and used to select areas of interest. Ultra-thin sections of selected areas were mounted on copper grids and examined on a Philips CM12 transmission electron microscope. This preliminary study indicates the presence of numerous lipid droplets (LD) (2), as roundish dark structures with electron-lucentstreaks, uniformly distributed and densely packed in the antral follicles oocyte’s cytoplasm in the ovaries of Se-treated group (Figure1). These structures, containing the dark precipitate which was not detected in cytoplasm or other organelles, were placed in the close vicinity of mitochondria and numerous vacuoles. In contrast, these structures in control group appeared quite different, electron-lucent, various in size and randomly distributed in cytoplasm. These results indicate that Se-treatment induce the heterogeneity in size, distribution and lipid composition of LD in the antral follicle oocytes. In the light of the impact of Se-treatment on the serum lipid content (3), our ongoing research should further clarify the impact of potential lipid profile alteration in ovaries on process of oogenesis and folliculogenesis.
PB  - Ruđer Bošković Institute and Croatian Microscopy Society
C3  - 13th Multinational Congress on Microscopy
T1  - Selenium induces accumulation of lipid droplets in antral follicles of porcine ovaries
EP  - 228
SP  - 227
UR  - https://hdl.handle.net/21.15107/rcub_rimsi_2604
ER  - 

@conference{
author = "Danilović Luković, Jelena and Lazarević, Anita and Bogdanović, Maja and Abadijeva, Desislava and Atansasova, Milena and Gennadiy, Boryaev and Kistanova, Elena and Korać, Aleksandra",
year = "2017",
abstract = "The selenium (Se) is an essential microelement included in diet for reproductive swine female. It is known that Se has an important role in antioxidative defense and maintenance of ovarian tissue in pathological conditions (1) though the information how it could be involved in healthy reproduction of female is limited. The present work is aimed to study the effect of injective application of organic compound selenopyran on ultrastructure of antral follicles of the porcine’s ovary. The experiment was conducted with 18 gilts of Danube white breed, ages between 120 - 228 days, divided into two groups each consisting of 9 animals. The animals received equal basal diets without selenium additives (Se content was 15 mg per kg of forage). The experimental gilts (Se-treated) were injected intramuscularly with oil solution of selenopyran (9-phenyl-symmetrical octahydroselenoxanthene) once per month (0.1 mg Se/kg live weight). After euthanasia of animals, tissue from one ovary of each animal was fixed in 4% glutaraldehyde, post-fixed in 1% osmium tetroxide, routinely dehydrated and embedded in Durcupan. Semi-thin sections were stained with Toluidine blue and used to select areas of interest. Ultra-thin sections of selected areas were mounted on copper grids and examined on a Philips CM12 transmission electron microscope. This preliminary study indicates the presence of numerous lipid droplets (LD) (2), as roundish dark structures with electron-lucentstreaks, uniformly distributed and densely packed in the antral follicles oocyte’s cytoplasm in the ovaries of Se-treated group (Figure1). These structures, containing the dark precipitate which was not detected in cytoplasm or other organelles, were placed in the close vicinity of mitochondria and numerous vacuoles. In contrast, these structures in control group appeared quite different, electron-lucent, various in size and randomly distributed in cytoplasm. These results indicate that Se-treatment induce the heterogeneity in size, distribution and lipid composition of LD in the antral follicle oocytes. In the light of the impact of Se-treatment on the serum lipid content (3), our ongoing research should further clarify the impact of potential lipid profile alteration in ovaries on process of oogenesis and folliculogenesis.",
publisher = "Ruđer Bošković Institute and Croatian Microscopy Society",
journal = "13th Multinational Congress on Microscopy",
title = "Selenium induces accumulation of lipid droplets in antral follicles of porcine ovaries",
pages = "228-227",
url = "https://hdl.handle.net/21.15107/rcub_rimsi_2604"
}

Danilović Luković, J., Lazarević, A., Bogdanović, M., Abadijeva, D., Atansasova, M., Gennadiy, B., Kistanova, E.,& Korać, A.. (2017). Selenium induces accumulation of lipid droplets in antral follicles of porcine ovaries. in 13th Multinational Congress on Microscopy
Ruđer Bošković Institute and Croatian Microscopy Society., 227-228.
https://hdl.handle.net/21.15107/rcub_rimsi_2604

Danilović Luković J, Lazarević A, Bogdanović M, Abadijeva D, Atansasova M, Gennadiy B, Kistanova E, Korać A. Selenium induces accumulation of lipid droplets in antral follicles of porcine ovaries. in 13th Multinational Congress on Microscopy. 2017;:227-228.
https://hdl.handle.net/21.15107/rcub_rimsi_2604 .

Danilović Luković, Jelena, Lazarević, Anita, Bogdanović, Maja, Abadijeva, Desislava, Atansasova, Milena, Gennadiy, Boryaev, Kistanova, Elena, Korać, Aleksandra, "Selenium induces accumulation of lipid droplets in antral follicles of porcine ovaries" in 13th Multinational Congress on Microscopy (2017):227-228,
https://hdl.handle.net/21.15107/rcub_rimsi_2604 .

TY  - JOUR
AU  - Danilović Luković, Jelena
AU  - Korać, Aleksandra
AU  - Milošević, Ivan
AU  - Lužajić, Tijana
AU  - Puškaš, Nela
AU  - Kovačević Filipović, Milica
PY  - 2016
UR  - http://rimsi.imsi.bg.ac.rs/handle/123456789/2446
AB  - tThyroid hormones (TH) are one of the key factors for normal prenatal development in mammals. Previ-ously, we showed that subclinical maternal hypothyroidism leads to premature atresia of ovarian folliclesin female rat offspring in the pre-pubertal and pubertal periods. The influence of decreased concentra-tion of TH on primordial follicles pool formation during neonatal and early infantile period of rat pupswas not investigated previously. Maternal hypothyroidism during pregnancy has irreversible negativeinfluence on primordial follicles pool formation and population of resting oocytes in female rat offspring.The study was done on neonatal and early infantile control (n-10) and hypothyroid (n-10) female ratpups derived from control (n-6) and propylthiouracil (PTU) treated pregnant dams (n-6), respectively.Ovaries of all pups were removed and processed for light and transmission electron microscopy (TEM).Number of nests, oogonia and oocytes per nest, primordial, primary, secondary and preantral follicleswere determined. Screening for overall calcium presence in ovarian tissue was done using Alizarin redstaining. Morphology and volume density of nucleus, mitochondria and smooth endoplasmic reticulum(sER) in the oocytes in primordial follicles was also assessed. Caspase-3 and terminal deoxynucleotidyltransferase dUTP nick end labelling (TUNEL), both markers for apoptosis, and proliferating cell nuclearantigen (PCNA) for proliferation were determined in oocytes and granulosa cells in different type of fol-licles. In neonatal period, ovaries of hypothyroid pups had a decreased number of oogonia, oocytes andnests, an increased number of primordial follicles and a decreased number of primary and secondary fol-licles, while in early infantile period, increased number of primary, secondary and preantral follicles werefound. Alizarin red staining was intense in hypothyroid neonatal rats that also had the highest content ofdilated sER. Number of mitochondria with altered morphology in both groups of hypothyroid pups wasincreased. Apoptosis markers have not shown significant difference between groups but PCNA had anincreased expression in the oocytes and granulosa cells in primordial follicles of hypothyroid rats. Lightand electron microscopy analysis indicate that previously detected premature ovarian follicular atresia inpre-pubertal and pubertal hypothyroid rats is preceded with premature formation of primordial folliclesfollowed by slight changes on sER and mitochondria in examined oocytes, and increased expression of PCNA.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Micron
T1  - Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach
EP  - 42
SP  - 33
VL  - 90
DO  - 10.1016/j.micron.2016.08.007
ER  - 

@article{
author = "Danilović Luković, Jelena and Korać, Aleksandra and Milošević, Ivan and Lužajić, Tijana and Puškaš, Nela and Kovačević Filipović, Milica",
year = "2016",
abstract = "tThyroid hormones (TH) are one of the key factors for normal prenatal development in mammals. Previ-ously, we showed that subclinical maternal hypothyroidism leads to premature atresia of ovarian folliclesin female rat offspring in the pre-pubertal and pubertal periods. The influence of decreased concentra-tion of TH on primordial follicles pool formation during neonatal and early infantile period of rat pupswas not investigated previously. Maternal hypothyroidism during pregnancy has irreversible negativeinfluence on primordial follicles pool formation and population of resting oocytes in female rat offspring.The study was done on neonatal and early infantile control (n-10) and hypothyroid (n-10) female ratpups derived from control (n-6) and propylthiouracil (PTU) treated pregnant dams (n-6), respectively.Ovaries of all pups were removed and processed for light and transmission electron microscopy (TEM).Number of nests, oogonia and oocytes per nest, primordial, primary, secondary and preantral follicleswere determined. Screening for overall calcium presence in ovarian tissue was done using Alizarin redstaining. Morphology and volume density of nucleus, mitochondria and smooth endoplasmic reticulum(sER) in the oocytes in primordial follicles was also assessed. Caspase-3 and terminal deoxynucleotidyltransferase dUTP nick end labelling (TUNEL), both markers for apoptosis, and proliferating cell nuclearantigen (PCNA) for proliferation were determined in oocytes and granulosa cells in different type of fol-licles. In neonatal period, ovaries of hypothyroid pups had a decreased number of oogonia, oocytes andnests, an increased number of primordial follicles and a decreased number of primary and secondary fol-licles, while in early infantile period, increased number of primary, secondary and preantral follicles werefound. Alizarin red staining was intense in hypothyroid neonatal rats that also had the highest content ofdilated sER. Number of mitochondria with altered morphology in both groups of hypothyroid pups wasincreased. Apoptosis markers have not shown significant difference between groups but PCNA had anincreased expression in the oocytes and granulosa cells in primordial follicles of hypothyroid rats. Lightand electron microscopy analysis indicate that previously detected premature ovarian follicular atresia inpre-pubertal and pubertal hypothyroid rats is preceded with premature formation of primordial folliclesfollowed by slight changes on sER and mitochondria in examined oocytes, and increased expression of PCNA.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Micron",
title = "Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach",
pages = "42-33",
volume = "90",
doi = "10.1016/j.micron.2016.08.007"
}

Danilović Luković, J., Korać, A., Milošević, I., Lužajić, T., Puškaš, N.,& Kovačević Filipović, M.. (2016). Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach. in Micron
Pergamon-Elsevier Science Ltd, Oxford., 90, 33-42.
https://doi.org/10.1016/j.micron.2016.08.007

Danilović Luković J, Korać A, Milošević I, Lužajić T, Puškaš N, Kovačević Filipović M. Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach. in Micron. 2016;90:33-42.
doi:10.1016/j.micron.2016.08.007 .

Danilović Luković, Jelena, Korać, Aleksandra, Milošević, Ivan, Lužajić, Tijana, Puškaš, Nela, Kovačević Filipović, Milica, "Altered state of primordial follicles in neonatal and early infantile rats due to maternal hypothyroidism: Light and electron microscopy approach" in Micron, 90 (2016):33-42,
https://doi.org/10.1016/j.micron.2016.08.007 . .