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Article ; Online: Manipulation of fractionalized charge in the metastable topologically entangled state of a doped Wigner crystal.

Mraz, Anze / Diego, Michele / Kranjec, Andrej / Vodeb, Jaka / Karpov, Peter / Gerasimenko, Yaroslav / Ravnik, Jan / Vaskivskyi, Yevhenii / Venturini, Rok / Kabanov, Viktor / Lipovšek, Benjamin / Topič, Marko / Vaskivskyi, Igor / Mihailovic, Dragan

Nature communications

2023 Volume 14, Issue 1, Page(s) 8214

Abstract: Metastability of many-body quantum states is rare and still poorly understood. An exceptional example is the low-temperature metallic state of the layered dichalcogenide 1T- ... ...

Abstract	Metastability of many-body quantum states is rare and still poorly understood. An exceptional example is the low-temperature metallic state of the layered dichalcogenide 1T-TaS
Language	English
Publishing date	2023-12-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43800-3
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Article ; Online: Autolysis Affects the Iron Cargo of Ferritins in Neurons and Glial Cells at Different Rates in the Human Brain.

Sunkara, Sowmya / Radulović, Snježana / Lipovšek, Saška / Birkl, Christoph / Eggenreich, Stefan / Birkl-Toeglhofer, Anna Maria / Schinagl, Maximilian / Funk, Daniel / Stöger-Pollach, Michael / Haybaeck, Johannes / Goessler, Walter / Ropele, Stefan / Leitinger, Gerd

Cellular and molecular neurobiology

2023 Volume 43, Issue 6, Page(s) 2909–2923

Abstract: Iron is known to accumulate in neurological disorders, so a careful balance of the iron concentration is essential for healthy brain functioning. An imbalance in iron homeostasis could arise due to the dysfunction of proteins involved in iron homeostasis. ...

Abstract	Iron is known to accumulate in neurological disorders, so a careful balance of the iron concentration is essential for healthy brain functioning. An imbalance in iron homeostasis could arise due to the dysfunction of proteins involved in iron homeostasis. Here, we focus on ferritin-the primary iron storage protein of the brain. In this study, we aimed to improve a method to measure ferritin-bound iron in the human post-mortem brain, and to discern its distribution in particular cell types and brain regions. Though it is known that glial cells and neurons differ in their ferritin concentration, the change in the number and distribution of iron-filled ferritin cores between different cell types during autolysis has not been revealed yet. Here, we show the cellular and region-wide distribution of ferritin in the human brain using state-of-the-art analytical electron microscopy. We validated the concentration of iron-filled ferritin cores to the absolute iron concentration measured by quantitative MRI and inductively coupled plasma mass spectrometry. We show that ferritins lose iron from their cores with the progression of autolysis whereas the overall iron concentrations were unaffected. Although the highest concentration of ferritin was found in glial cells, as the total ferritin concentration increased in a patient, ferritin accumulated more in neurons than in glial cells. Summed up, our findings point out the unique behaviour of neurons in storing iron during autolysis and explain the differences between the absolute iron concentrations and iron-filled ferritin in a cell-type-dependent manner in the human brain. The rate of loss of the iron-filled ferritin cores during autolysis is higher in neurons than in glial cells.
MeSH term(s)	Humans ; Iron/metabolism ; Ferritins/metabolism ; Neuroglia/metabolism ; Neurons/metabolism ; Brain/metabolism
Chemical Substances	Iron (E1UOL152H7) ; Ferritins (9007-73-2)
Language	English
Publishing date	2023-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	283404-2
ISSN	1573-6830 ; 0272-4340
ISSN (online)	1573-6830
ISSN	0272-4340
DOI	10.1007/s10571-023-01332-w
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Zs.A 1727: Show issues

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Article ; Online: Adnectins: engineered target-binding protein therapeutics.

Lipovsek, D

Protein engineering, design & selection : PEDS

2010 Volume 24, Issue 1-2, Page(s) 3–9

Abstract: ... D, is being evaluated in Phase II clinical trials for efficacy in several oncology indications. ...

Abstract	Adnectins™ are a new family of therapeutic proteins based on the 10th fibronectin type III domain, and designed to bind with high affinity and specificity to therapeutically relevant targets. Adnectins share with antibody variable domains a beta-sheet sandwich fold with diversified loops, but differ from antibodies in primary sequence and have a simpler, single-domain structure without disulfide bonds. As a consequence, Adnectins bind targets with affinity and specificity as high as those of antibodies, but are easier to manipulate genetically and compatible with bacterial expression systems. Adnectins that bind macromolecular targets with nanomolar and picomolar affinity have been selected using in vitro evolution methods, including mRNA display, phage display and yeast display. CT-322, a PEGylated, anti-angiogenic Adnectin that binds vascular endothelial growth factor (VEGF) receptor 2 and blocks its interaction with VEGF A, C and D, is being evaluated in Phase II clinical trials for efficacy in several oncology indications.
MeSH term(s)	Animals ; Fibronectins/chemistry ; Fibronectins/genetics ; Fibronectins/therapeutic use ; Humans ; Models, Molecular ; Protein Binding ; Protein Engineering/methods ; Protein Structure, Tertiary ; Vascular Endothelial Growth Factors/metabolism
Chemical Substances	Fibronectins ; Vascular Endothelial Growth Factors
Language	English
Publishing date	2010-11-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1466729-0
ISSN	1741-0134 ; 1741-0126
ISSN (online)	1741-0134
ISSN	1741-0126
DOI	10.1093/protein/gzq097
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Article ; Online: Analysis and optimization of light outcoupling in OLEDs with external hierarchical textures.

Kovačič, Milan / Samigullina, Dinara / Bouchard, Felix / Krč, Janez / Lipovšek, Benjamin / Soldera, Marcos / Lasagni, Andrés Fabián / Reineke, Sebastian / Topič, Marko

Optics express

2021 Volume 29, Issue 15, Page(s) 23701–23716

Abstract: Hierarchical textures (combining 2D periodic large and small micro textures) as an external outcoupling solution for OLEDs have been researched, both experimentally and by optical simulations. For the case of a red bottom emitting OLED, different ... ...

Abstract	Hierarchical textures (combining 2D periodic large and small micro textures) as an external outcoupling solution for OLEDs have been researched, both experimentally and by optical simulations. For the case of a red bottom emitting OLED, different hierarchical textures were fabricated using laser-based methods and a replication step and applied to the OLED substrate, resulting in an increased light outcoupling. Laboratory-size OLED devices with applied textured foils show a smaller increase in efficiency compared to the final large area devices. The results show that the full exploitation of textured foils in laboratory-size samples is mainly limited by the lateral size of the thin film stack area and by limited light collection area of the measuring equipment. Modeling and simulations are used to further evaluate the full prospective of hierarchical textures in large area OLED devices. Optimization of hierarchical textures is done by simultaneously changing the aspect ratios of the small and large textures and a potential of 57% improvement in EQE compared to devices without applied textures is predicted by simulations. Optimized hierarchical textures show similar outcoupling efficiencies compared to optimized single textures, while on the other hand hierarchical textures require less pronounced features, lower aspect ratios, compared to single textures to achieve the same efficiencies. Hierarchical textures also help in eliminating flat parts that limit outcoupling efficiency. Finally, the limiting factors that prevent higher outcoupling are addressed. We show that the dominant factor is non-ideal reflection from the organic thin film stack due to parasitic absorption. In addition, possible ways to further increase the outcoupling from a thick substrate are indicated.
Language	English
Publishing date	2021-09-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	1491859-6
ISSN	1094-4087 ; 1094-4087
ISSN (online)	1094-4087
ISSN	1094-4087
DOI	10.1364/OE.428021
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Article ; Online: Conformational Assessment of Adnectin and Adnectin-Drug Conjugate by Hydrogen/Deuterium Exchange Mass Spectrometry.

Huang, Richard Y-C / O'Neil, Steven R / Lipovšek, Daša / Chen, Guodong

Journal of the American Society for Mass Spectrometry

2018 Volume 29, Issue 7, Page(s) 1524–1531

Abstract: Higher-order structure (HOS) characterization of therapeutic protein-drug conjugates for comprehensive assessment of conjugation-induced protein conformational changes is an important consideration in the biopharmaceutical industry to ensure proper ... ...

Abstract	Higher-order structure (HOS) characterization of therapeutic protein-drug conjugates for comprehensive assessment of conjugation-induced protein conformational changes is an important consideration in the biopharmaceutical industry to ensure proper behavior of protein therapeutics. In this study, conformational dynamics of a small therapeutic protein, adnectin 1, together with its drug conjugate were characterized by hydrogen/deuterium exchange mass spectrometry (HDX-MS) with different spatial resolutions. Top-down HDX allows detailed assessment of the residue-level deuterium content in the payload conjugation region. HDX-MS dataset revealed the ability of peptide-based payload/linker to retain deuterium in HDX experiments. Combined results from intact, top-down, and bottom-up HDX indicated no significant conformational changes of adnectin 1 upon payload conjugation. Graphical Abstract ᅟ.
MeSH term(s)	Deuterium Exchange Measurement/methods ; Immunoconjugates/analysis ; Immunoconjugates/chemistry ; Mass Spectrometry/methods ; Models, Molecular ; Protein Conformation ; Single-Domain Antibodies/analysis ; Single-Domain Antibodies/chemistry
Chemical Substances	Immunoconjugates ; Single-Domain Antibodies
Language	English
Publishing date	2018-05-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1007/s13361-018-1966-2
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Zs.A 4618: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 241: Show issues

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Article ; Online: Patch-seq: Past, Present, and Future.

Lipovsek, Marcela / Bardy, Cedric / Cadwell, Cathryn R / Hadley, Kristen / Kobak, Dmitry / Tripathy, Shreejoy J

The Journal of neuroscience : the official journal of the Society for Neuroscience

2021 Volume 41, Issue 5, Page(s) 937–946

Abstract: Single-cell transcriptomic approaches are revolutionizing neuroscience. Integrating this wealth of data with morphology and physiology, for the comprehensive study of neuronal biology, requires multiplexing gene expression data with complementary ... ...

Abstract	Single-cell transcriptomic approaches are revolutionizing neuroscience. Integrating this wealth of data with morphology and physiology, for the comprehensive study of neuronal biology, requires multiplexing gene expression data with complementary techniques. To meet this need, multiple groups in parallel have developed "Patch-seq," a modification of whole-cell patch-clamp protocols that enables mRNA sequencing of cell contents after electrophysiological recordings from individual neurons and morphologic reconstruction of the same cells. In this review, we first outline the critical technical developments that enabled robust Patch-seq experimental efforts and analytical solutions to interpret the rich multimodal data generated. We then review recent applications of Patch-seq that address novel and long-standing questions in neuroscience. These include the following: (1) targeted study of specific neuronal populations based on their anatomic location, functional properties, lineage, or a combination of these factors; (2) the compilation and integration of multimodal cell type atlases; and (3) the investigation of the molecular basis of morphologic and functional diversity. Finally, we highlight potential opportunities for further technical development and lines of research that may benefit from implementing the Patch-seq technique. As a multimodal approach at the intersection of molecular neurobiology and physiology, Patch-seq is uniquely positioned to directly link gene expression to brain function.
MeSH term(s)	Animals ; Cells, Cultured ; Electrophysiological Phenomena/physiology ; Forecasting ; Humans ; Neurons/physiology ; Patch-Clamp Techniques/methods ; Patch-Clamp Techniques/trends ; Sequence Analysis, RNA/methods ; Sequence Analysis, RNA/trends ; Single-Cell Analysis/methods ; Single-Cell Analysis/trends ; Transcriptome/physiology
Language	English
Publishing date	2021-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1653-20.2020
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Zs.A 1668: Show issues

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Article ; Online: Design for Solubility May Reveal Induction of Amide Hydrogen/Deuterium Exchange by Protein Self-Association.

Trainor, Kyle / Doyle, Colleen M / Metcalfe-Roach, Avril / Steckner, Julia / Lipovšek, Daša / Malakian, Heather / Langley, David / Krystek, Stanley R / Meiering, Elizabeth M

Journal of molecular biology

2021 Volume 434, Issue 2, Page(s) 167398

Abstract: Structural heterogeneity often constrains the characterization of aggregating proteins to indirect or low-resolution methods, obscuring mechanistic details of association. Here, we report progress in understanding the aggregation of Adnectins, engineered ...

Abstract	Structural heterogeneity often constrains the characterization of aggregating proteins to indirect or low-resolution methods, obscuring mechanistic details of association. Here, we report progress in understanding the aggregation of Adnectins, engineered binding proteins with an immunoglobulin-like fold. We rationally design Adnectin solubility and measure amide hydrogen/deuterium exchange (HDX) under conditions that permit transient protein self-association. Protein-protein binding commonly slows rates of HDX; in contrast, we find that Adnectin association may induce faster HDX for certain amides, particularly in the C-terminal β-strand. In aggregation-prone proteins, we identify a pattern of very different rates of amide HDX for residues linked by reciprocal hydrogen bonds in the native structure. These results may be explained by local loss of native structure and formation of an inter-protein interface. Amide HDX induced by self-association, detected here by deliberate modulation of propensity for such interactions, may be a general phenomenon with the potential to expose mechanisms of aggregation by diverse proteins.
MeSH term(s)	Amides/chemistry ; Amino Acid Sequence ; Deuterium/chemistry ; Hydrogen/chemistry ; Hydrogen Bonding ; Models, Molecular ; Protein Binding ; Proteins/chemistry ; Solubility
Chemical Substances	Amides ; Proteins ; Hydrogen (7YNJ3PO35Z) ; Deuterium (AR09D82C7G)
Language	English
Publishing date	2021-12-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80229-3
ISSN	1089-8638 ; 0022-2836
ISSN (online)	1089-8638
ISSN	0022-2836
DOI	10.1016/j.jmb.2021.167398
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Zs.A 867: Show issues

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Article: Larval morphology of the antlion Myrmecaelurus trigrammus (Pallas, 1771) (Neuroptera, Myrmeleontidae), with notes on larval biology.

Devetak, Dušan / Klokočovnik, Vesna / Lipovšek, Saška / Bock, Elisabeth / Leitinger, Gerd

Zootaxa

2015 Volume 3641, Page(s) 491–500

Abstract: Morphology and behaviour of third instar larvae of the Holomediterranean antlion species Myrmecaelurus trigranunus (Pallas) are described. Larvae are facultative pit-builders, they either ambush their prey at the surface, or dig pitfall traps that prey ... ...

Abstract	Morphology and behaviour of third instar larvae of the Holomediterranean antlion species Myrmecaelurus trigranunus (Pallas) are described. Larvae are facultative pit-builders, they either ambush their prey at the surface, or dig pitfall traps that prey fall in to. Dark brown spots on dorsal and ventral sides of the head and on dorsal side of the thorax are characteristic of the larvae. Eye tubercles are not prominent. Jaws are equipped with long bristles, campaniform sensilla, sensilla coeloconica, and digitiform sensilla. A unique feature is the shape of the tips of all three teeth that is screw-like with a polyhedral surface. The body surface is covered with longitudinally grooved bristles and plumose hairs. On the tip of the antennae and on terminal and subterminal parts of labial palps sensilla basiconica occur. On the 9th abdominal segment there are two bulges, each of them bearing four digging bristles. Non-prominent eye tubercles and numerous mandibular bristles are morphological traits of pit-builders. Most of the behavioural traits are related to pit builders, whereas forward movement, waiting for prey without a pit and frequent changing of ambush location are traits of non-pit builders.
MeSH term(s)	Animal Structures/anatomy & histology ; Animal Structures/growth & development ; Animals ; Body Size ; Catfishes/anatomy & histology ; Catfishes/classification ; Catfishes/growth & development ; Female ; Insecta/anatomy & histology ; Insecta/classification ; Insecta/growth & development ; Larva/anatomy & histology ; Larva/classification ; Larva/growth & development ; Male ; Organ Size
Language	English
Publishing date	2015-07-23
Publishing country	New Zealand
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1175-5326
ISSN	1175-5326
DOI	10.11646/zootaxa.3641.4.14
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Article ; Online: Towards understanding partial adaptation to the subterranean habitat in the European cave spider, Meta menardi: An ecocytological approach.

Lipovšek, Saška / Leitinger, Gerd / Janžekovič, Franc / Kozel, Peter / Dariš, Barbara / Perc, Matjaž / Devetak, Dušan / Weiland, Nina / Novak, Tone

Scientific reports

2019 Volume 9, Issue 1, Page(s) 9121

Abstract: The European cave spider, Meta menardi, is a representative of the troglophiles, i.e. non-strictly subterranean organisms. Our aim was to interpret the cytological results from an ecological perspective, and provide a synthesis of the hitherto knowledge ... ...

Abstract	The European cave spider, Meta menardi, is a representative of the troglophiles, i.e. non-strictly subterranean organisms. Our aim was to interpret the cytological results from an ecological perspective, and provide a synthesis of the hitherto knowledge about M. menardi into a theory of key features marking it a troglophile. We studied ultrastructural changes of the midgut epithelial cells in individuals spending winter under natural conditions in caves, using light microscopy and TEM. The midgut diverticula epithelium consisted of secretory cells, digestive cells and adipocytes. During winter, gradual vacuolization of some digestive cells appeared, and some necrotic digestive cells and necrotic adipocytes appeared. This cytological information completes previous studies on M. menardi starved under controlled conditions in the laboratory. In experimental starvation and natural winter conditions, M. menardi gradually exploit reserve compounds from spherites, protein granules and through autophagy, and energy-supplying lipids and glycogen, as do many overwintering arthropods. We found no special cellular response to living in the habitat. Features that make it partly adapted to the subterranean habitat include starvation hardiness as a possible preadaptation, an extremely opportunistic diet, a partly reduced orb, tracking and capturing prey on bare walls and partly reduced tolerance to below-zero temperatures.
MeSH term(s)	Acclimatization ; Adaptation, Physiological ; Animals ; Ecosystem ; Female ; Male ; Seasons ; Spiders/physiology
Language	English
Publishing date	2019-06-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-45291-z
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Article ; Online: A Selection of Macrocyclic Peptides That Bind STING From an mRNA-Display Library With Split Degenerate Codons.

Lin, Chi-Wang / Harner, Mary J / Douglas, Andrew E / Lafont, Virginie / Yu, Fei / Lee, Ving G / Poss, Michael A / Swain, Joanna F / Wright, Martin / Lipovšek, Daša

Angewandte Chemie (International ed. in English)

2021 Volume 60, Issue 42, Page(s) 22640–22645

Abstract: Recent improvements in mRNA display have enabled the selection of peptides that incorporate non-natural amino acids, thus expanding the chemical diversity of macrocycles beyond what is accessible in nature. Such libraries have incorporated non-natural ... ...

Abstract	Recent improvements in mRNA display have enabled the selection of peptides that incorporate non-natural amino acids, thus expanding the chemical diversity of macrocycles beyond what is accessible in nature. Such libraries have incorporated non-natural amino acids at the expense of natural amino acids by reassigning their codons. Here we report an alternative approach to expanded amino-acid diversity that preserves all 19 natural amino acids (no methionine) and adds 6 non-natural amino acids, resulting in the highest sequence complexity reported to date. We have applied mRNA display to this 25-letter library to select functional macrocycles that bind human STING, a protein involved in immunoregulation. The resulting STING-binding peptides include a 9-mer macrocycle with a dissociation constant (K
MeSH term(s)	Amino Acid Sequence ; Amino Acids/chemistry ; Codon ; Cyclic AMP/chemistry ; Cyclic AMP/metabolism ; Cyclic GMP/chemistry ; Cyclic GMP/metabolism ; Dimerization ; Genetic Engineering ; Humans ; Kinetics ; Membrane Proteins/chemistry ; Membrane Proteins/metabolism ; Peptide Library ; Peptides, Cyclic/chemistry ; Peptides, Cyclic/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism
Chemical Substances	Amino Acids ; Codon ; Membrane Proteins ; Peptide Library ; Peptides, Cyclic ; RNA, Messenger ; STING1 protein, human ; Cyclic AMP (E0399OZS9N) ; Cyclic GMP (H2D2X058MU)
Language	English
Publishing date	2021-09-06
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.202103043
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