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1.
Proc Natl Acad Sci U S A ; 120(35): e2304294120, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37607226

ABSTRACT

Simulating the properties of many-body fermionic systems is an outstanding computational challenge relevant to material science, quantum chemistry, and particle physics.-5.4pc]Please note that the spelling of the following author names in the manuscript differs from the spelling provided in the article metadata: D. González-Cuadra, D. Bluvstein, M. Kalinowski, R. Kaubruegger, N. Maskara, P. Naldesi, T. V. Zache, A. M. Kaufman, M. D. Lukin, H. Pichler, B. Vermersch, Jun Ye, and P. Zoller. The spelling provided in the manuscript has been retained; please confirm. Although qubit-based quantum computers can potentially tackle this problem more efficiently than classical devices, encoding nonlocal fermionic statistics introduces an overhead in the required resources, limiting their applicability on near-term architectures. In this work, we present a fermionic quantum processor, where fermionic models are locally encoded in a fermionic register and simulated in a hardware-efficient manner using fermionic gates. We consider in particular fermionic atoms in programmable tweezer arrays and develop different protocols to implement nonlocal gates, guaranteeing Fermi statistics at the hardware level. We use this gate set, together with Rydberg-mediated interaction gates, to find efficient circuit decompositions for digital and variational quantum simulation algorithms, illustrated here for molecular energy estimation. Finally, we consider a combined fermion-qubit architecture, where both the motional and internal degrees of freedom of the atoms are harnessed to efficiently implement quantum phase estimation as well as to simulate lattice gauge theory dynamics.

2.
Science ; 376(6598): 1209-1215, 2022 06 10.
Article in English | MEDLINE | ID: mdl-35511943

ABSTRACT

Realizing quantum speedup for practically relevant, computationally hard problems is a central challenge in quantum information science. Using Rydberg atom arrays with up to 289 qubits in two spatial dimensions, we experimentally investigate quantum algorithms for solving the maximum independent set problem. We use a hardware-efficient encoding associated with Rydberg blockade, realize closed-loop optimization to test several variational algorithms, and subsequently apply them to systematically explore a class of graphs with programmable connectivity. We find that the problem hardness is controlled by the solution degeneracy and number of local minima, and we experimentally benchmark the quantum algorithm's performance against classical simulated annealing. On the hardest graphs, we observe a superlinear quantum speedup in finding exact solutions in the deep circuit regime and analyze its origins.

3.
Science ; 374(6572): 1242-1247, 2021 Dec 03.
Article in English | MEDLINE | ID: mdl-34855494

ABSTRACT

Quantum spin liquids, exotic phases of matter with topological order, have been a major focus in physics for the past several decades. Such phases feature long-range quantum entanglement that can potentially be exploited to realize robust quantum computation. We used a 219-atom programmable quantum simulator to probe quantum spin liquid states. In our approach, arrays of atoms were placed on the links of a kagome lattice, and evolution under Rydberg blockade created frustrated quantum states with no local order. The onset of a quantum spin liquid phase of the paradigmatic toric code type was detected by using topological string operators that provide direct signatures of topological order and quantum correlations. Our observations enable the controlled experimental exploration of topological matter and protected quantum information processing.

4.
Hum Reprod ; 36(11): 2871-2882, 2021 10 18.
Article in English | MEDLINE | ID: mdl-34529796

ABSTRACT

STUDY QUESTION: What are the characteristics of patients with conceptions transplanted in childhood and adolescence? SUMMARY ANSWER: Insemination and conception after hematopoietic stem cell transplantation (HCT) in childhood or adolescence was possible, even after myeloablative conditioning regimes, although some patients required reproductive medicine support. WHAT IS KNOWN ALREADY: Preparative regimens of HCT are highly gonadotoxic, which leads to gonadal failure and pubertal development disorders. There are few population-based studies assessing the risk of future infertility in children after HCT. STUDY DESIGN, SIZE, DURATION: We conducted a retrospective study to investigate natural or assisted conceptions and their outcomes in patients <18 years old before their first transplantation who received HCT between 1995 and 2016 and were in the European Society for Blood and Marrow Transplantation (EBMT) registry. Adoptions were excluded from the analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Detailed information concerning pregnancy occurrences and outcomes were obtained by a separate questionnaire. Quantitative variables were presented as medians with their interquartile range (IQR) or range, and categorical variables were presented as frequencies and percentages. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 62 988 pediatric patients received a first HCT in EBMT centers between 1995 and 2016. Pregnancy was reported in 406 patients in the database. The median age at transplantation was 15.7 (range: 0.7-18) years, and the median age at declared conception was 25.0 (range: 16.3-38.8) years. Details concerning the first pregnancy and pregnancy outcome were obtained from 99 patients (24%) from the returned questionnaires. The median age at delivery or pregnancy interruption of the females was 23.0 (IQR: 20.8-27) years, with a median time after transplant of 10.7 (IQR: 6.6-15.4) years. Compared with the mean age of healthy women at their first child's birth (29 years old), the transplanted women delivered 5 years earlier (mean: 24.3 years). In terms of conception modality, 13/25 (52%) females conditioned with total body irradiation (TBI) and 50/52 (96%) of those conditioned without TBI conceived naturally. All seven male patients who had been conditioned with TBI achieved fatherhood but required assisted fertilization or used their cryopreserved sperm. In the females, 63/70 (90%) of all conceptions resulted in a live birth, 49/63 (84.5%) were at term and 43/46 (93%) had normal birthweight. Cesarean delivery was performed in 9/61 (15%) especially in women who had received a myeloablative regimen. LIMITATIONS, REASONS FOR CAUTION: In the EBMT pediatric dataset, the age at last follow-up or death was <17 years for 75% of the patients, therefore a longer follow-up for all patients would be necessary to calculate the cumulative incidence of conception for patients transplanted during childhood and allow all patients to realize their reproductive willingness/potential. WIDER IMPLICATIONS OF THE FINDINGS: Reproductive health surveillance and fertility preservation counseling are important in younger transplanted patients. Our results showed that there is a window of opportunity to conceive naturally or with reproductive medicine support. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by the 'Stiftung für krebskranke Kinder Regio Basiliensis', Basel, Switzerland. All authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Subject(s)
Hematopoietic Stem Cell Transplantation , Pregnancy Outcome , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Live Birth , Male , Pregnancy , Retrospective Studies
5.
Science ; 365(6453): 570-574, 2019 08 09.
Article in English | MEDLINE | ID: mdl-31395778

ABSTRACT

Quantum entanglement involving coherent superpositions of macroscopically distinct states is among the most striking features of quantum theory, but its realization is challenging because such states are extremely fragile. Using a programmable quantum simulator based on neutral atom arrays with interactions mediated by Rydberg states, we demonstrate the creation of "Schrödinger cat" states of the Greenberger-Horne-Zeilinger (GHZ) type with up to 20 qubits. Our approach is based on engineering the energy spectrum and using optimal control of the many-body system. We further demonstrate entanglement manipulation by using GHZ states to distribute entanglement to distant sites in the array, establishing important ingredients for quantum information processing and quantum metrology.

6.
Int J Pharm ; 547(1-2): 169-180, 2018 Aug 25.
Article in English | MEDLINE | ID: mdl-29782971

ABSTRACT

In contact-less printing, such as piezo-electric drop on demand printing used in the study, the drop formation process is independent of the substrate. This means that having developed a printable formulation, printed pharmaceutical dosage forms can be obtained on any pharmaceutical grade substrate, such as polymer-based films. In this work we evaluated eight different oral films based on their suitability as printing substrates for sodium picosulfate. The different polymer films were compared regarding printed spot morphology, chemical stability and dissolution profile. The morphology of printed sodium picosulfate was investigated with scanning electron microscopy and optical coherence tomography. The spreading of the deposited drops was found to be governed by the contact angle of the ink with the substrate. The form of the sodium picosulfate drops changed on microcrystalline cellulose films at ambient conditions over 8 weeks and stayed unchanged on other tested substrates. Sodium picosulfate remained amorphous on all substrates according to small and wide angle X-ray scattering, differential scanning calorimetry and polarized light microscopy measurements. The absence of chemical interactions between the drug and substrates, as indicated by infrared spectroscopy, makes all tested substrates suitable for printing sodium picosulfate onto them.


Subject(s)
Drug Compounding/methods , Drug Delivery Systems , Printing , Administration, Oral , Cellulose/chemistry , Citrates/chemistry , Drug Liberation , Gelatin/chemistry , Hypromellose Derivatives/chemistry , Organometallic Compounds/chemistry , Picolines/chemistry , Titanium/chemistry , Wettability
7.
Phys Rev Lett ; 119(2): 023603, 2017 Jul 14.
Article in English | MEDLINE | ID: mdl-28753358

ABSTRACT

We demonstrate that two-dimensional atomic emitter arrays with subwavelength spacing constitute topologically protected quantum optical systems where the photon propagation is robust against large imperfections while losses associated with free space emission are strongly suppressed. Breaking time-reversal symmetry with a magnetic field results in gapped photonic bands with nontrivial Chern numbers and topologically protected, long-lived edge states. Due to the inherent nonlinearity of constituent emitters, such systems provide a platform for exploring quantum optical analogs of interacting topological systems.

8.
Phys Rev Lett ; 118(13): 133601, 2017 Mar 31.
Article in English | MEDLINE | ID: mdl-28409953

ABSTRACT

We describe a quantum state transfer protocol, where a quantum state of photons stored in a first cavity can be faithfully transferred to a second distant cavity via an infinite 1D waveguide, while being immune to arbitrary noise (e.g., thermal noise) injected into the waveguide. We extend the model and protocol to a cavity QED setup, where atomic ensembles, or single atoms representing quantum memory, are coupled to a cavity mode. We present a detailed study of sensitivity to imperfections, and apply a quantum error correction protocol to account for random losses (or additions) of photons in the waveguide. Our numerical analysis is enabled by matrix product state techniques to simulate the complete quantum circuit, which we generalize to include thermal input fields. Our discussion applies both to photonic and phononic quantum networks.

9.
J Fish Biol ; 90(1): 396-416, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27804138

ABSTRACT

This study investigated whether the fish communities inhabiting shallow non-vegetated habitats in two divergent bays in a subtropical World Heritage Site estuarine system differed according to wet (spring-summer) and dry (autumn-winter) seasons or polyhaline and mesohaline zones, within the broader objective of facilitating spatio-temporal management. Species richness (total of 74 taxa; total length, LT = 11-552 mm) and abundance (51 109 individuals) were mostly greater in the wet than dry season and in polyhaline than mesohaline areas. There was a major effect of rainfall on recruitment, particularly among transient fishes, which could be the result of enhanced survival of young via greater productivity (food resources) and protection from predators (via turbidity reducing visual cues). Salinity had strong interactive effects with rainfall and temperature in one bay, with greater species richness and overall abundances as well as large abundances of four key species [Anchoa januaria and Atherinella brasiliensis (pelagic residents), Cetengraulis edentulus (pelagic transient) and Diapterus rhombeus (demersal transient)] during the wet season in polyhaline areas; possibly reflecting a biodiversity hotspot that might be affected by distance to the estuary mouth and convergence hydrology. Regionally, the results support enforcing spatio-temporal restrictions to minimize anthropogenic activities within statutory (but not always enforced) protected areas. Globally, the data reiterate the need to identify and understand biotic and abiotic effects on estuarine ichthyofaunal distributions and abundances as a precursor to their management.


Subject(s)
Biodiversity , Estuaries , Fishes/physiology , Seasons , Animals , Bays , Behavior, Animal , Salinity , Temperature
10.
Phys Rev Lett ; 117(23): 233001, 2016 Dec 02.
Article in English | MEDLINE | ID: mdl-27982643

ABSTRACT

We discuss the generation of subwavelength optical barriers on the scale of tens of nanometers, as conservative optical potentials for cold atoms. These arise from nonadiabatic corrections to Born-Oppenheimer potentials from dressed "dark states" in atomic Λ configurations. We illustrate the concepts with a double layer potential for atoms obtained from inserting an optical subwavelength barrier into a well generated by an off-resonant optical lattice, and discuss bound states of pairs of atoms interacting via magnetic dipolar interactions. The subwavelength optical barriers represent an optical "Kronig-Penney" potential. We present a detailed study of the band structure in optical Kronig-Penney potentials, including decoherence from spontaneous emission and atom loss to open "bright" channels.

11.
Bone Marrow Transplant ; 51(8): 1093-100, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27042837

ABSTRACT

Flow cytometric routine CD34 analysis enumerates hematopoietic stem and progenitor cells irrespective of their subpopulations although this might predict engraftment dynamics and immune reconstitution. We established a multi-color CD34 assay containing CD133, CD45RA, CD10, CD38 and CD33. We examined PBSC, donor bone marrow (BMd) and BM of patients 1 year after allografting (BM1y) regarding their CD34 subset composition, which differed significantly amongst those materials: the early CD45RA(-)CD133(+)CD38(low) subpopulations were significantly more frequent in PBSC than in BMd, and very low in BM1y. Vice versa, clearly more committed CD34 stages prevailed in BM, particularly in BM1y where the proportion of multi-lymphoid and CD38(++) B-lymphoid precursors was highest (mean 59%). CD33 was expressed at different intensity on CD45RA(±)CD133(±) subsets allowing discrimination of earlier from more committed myeloid precursors. Compared with conventional CD34(+) cell enumeration, the presented multi-color phenotyping is a qualitative approach defining different CD34 subtypes in any CD34 source. Its potential impact to predict engraftment kinetics and immune reconstitution has to be evaluated in future studies.


Subject(s)
Antigens, CD34/analysis , Antigens, CD/analysis , Hematopoietic Stem Cells/immunology , Immunophenotyping , Adolescent , Adult , Aged , Allografts/immunology , Bone Marrow Cells/immunology , Child , Child, Preschool , Female , Flow Cytometry , Hematopoietic Stem Cell Transplantation/methods , Humans , Infant , Male , Middle Aged , Peripheral Blood Stem Cells/immunology , Specimen Handling , Young Adult
12.
Vox Sang ; 111(2): 187-96, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27037580

ABSTRACT

BACKGROUND AND OBJECTIVES: Our post-thaw cell recovery rates differed substantially in interlaboratory comparisons of identical samples, potentially due to different temperatures during cell staining. MATERIALS AND METHODS: Viable CD34(+) cells and leucocyte (WBC) subtypes were quantified by multiparameter single-platform flow cytometry in leucapheresis products collected from 30 adult lymphoma and myeloma patients, and from 10 paediatric patients. After thawing, cells were prepared for analysis within 30 min between thawing and acquisition, at either 4°C or at room temperature. RESULTS: For cell products cryopreserved in conventional freezing medium (10% final DMSO), viable cell recovery was clearly lower after staining at 4°C than at RT. Of all WBC subtypes analysed, CD4(+) T cells showed the lowest median recovery of 4% (4°C) vs. 25% (RT), followed by CD3, CD34 and CD8 cells. The recovery was highest for CD3γδ cells with 44% (4°C) vs. 71% (RT). In the 10 samples cryopreserved in synthetic freezing medium (5% final DMSO), median recovery rates were 89% for viable CD34 (both at 4°C and RT) and 79% (4°C) vs 68% (RT) for WBC. CONCLUSIONS: The post-thaw environment and, potentially, the cryoprotectant impact the outcome of cell enumeration, and results from the analysis tube may not be representative of the cells infused into a patient.


Subject(s)
Leukocytes/cytology , Adult , Antigens, CD34/metabolism , Flow Cytometry , Freezing , Humans , Leukocytes/metabolism , Multiple Myeloma , Staining and Labeling , Temperature
13.
Int J Pharm ; 509(1-2): 518-527, 2016 Jul 25.
Article in English | MEDLINE | ID: mdl-26541301

ABSTRACT

We present our recent advancements in developing a viable manufacturing process for printed medicine. Our approach involves using a non-contact printing system that incorporates both piezoelectric- and solenoid valve-based inkjet printing technologies, to deliver both active and inactive pharmaceutical materials onto medical-graded orodispersible films. By using two complimentary inkjet technologies, we were able to dispense an extensive range of fluids, from aqueous drug solutions to viscous polymer coating materials. Essentially, we demonstrate printing of a wide range of formulations for patient-ready, orodispersible drug dosage forms, without the risk of drug degradation by ink heating and of substrate damages (by contact printing). In addition, our printing process has been optimized to ensure that the drug doses can be loaded onto the orally dissolvable films without introducing defects, such as holes or tears, while retaining a smooth surface texture that promotes patient adherence and allows for uniform post-coatings. Results show that our platform technology can address key issues in manufacturing orodispersible drug dosage forms and bring us closer to delivering personalized and precision medicine to targeted patient populations.


Subject(s)
Pharmaceutical Preparations/chemistry , Printing/methods , Technology, Pharmaceutical/methods , Administration, Oral , Chemistry, Pharmaceutical/methods , Dosage Forms , Drug Delivery Systems/methods , Excipients/chemistry , Pharmaceutical Solutions/chemistry , Precision Medicine/methods , Surface Properties , Viscosity
14.
Phys Rev Lett ; 109(2): 020505, 2012 Jul 13.
Article in English | MEDLINE | ID: mdl-23030143

ABSTRACT

We discuss a scheme to measure the many-body entanglement growth during quench dynamics with bosonic atoms in optical lattices. By making use of a 1D or 2D setup in which two copies of the same state are prepared, we show how arbitrary order Rényi entropies can be extracted by using tunnel coupling between the copies and measurement of the parity of on-site occupation numbers, as has been performed in recent experiments. We illustrate these ideas for a superfluid-Mott insulator quench in the Bose-Hubbard model, and also for hard-core bosons, and show that the scheme is robust against imperfections in the measurements.

15.
Braz J Biol ; 68(1): 37-43, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18470376

ABSTRACT

Tidal creeks are strongly influenced by tides and are therefore exposed to large differences in salinity and depth daily. Here we compare fish assemblages in tidal creeks between day and night in two tidal creeks in southern Brazil. Monthly day and night, simultaneous collections were carried out in both creeks using fyke nets. Clupeiformes tended to be caught more during the day. Cathorops spixii, Genidens genidens and Rypticus randalli tended to be caught at night. Sciaenidae also tended to be caught more during the night. In general, pelagic species were diurnal, while deep water species were nocturnal. These trends are probably due to a variety of causes, such as phylogeny, predation and net avoidance.


Subject(s)
Fishes/classification , Animals , Brazil , Circadian Rhythm , Population Dynamics , Seasons
16.
Braz. j. biol ; 68(1): 37-43, Feb. 2008. graf, tab
Article in English | LILACS | ID: lil-482181

ABSTRACT

Tidal creeks are strongly influenced by tides and are therefore exposed to large differences in salinity and depth daily. Here we compare fish assemblages in tidal creeks between day and night in two tidal creeks in southern Brazil. Monthly day and night, simultaneous collections were carried out in both creeks using fyke nets. Clupeiformes tended to be caught more during the day. Cathorops spixii, Genidens genidens and Rypticus randalli tended to be caught at night. Sciaenidae also tended to be caught more during the night. In general, pelagic species were diurnal, while deep water species were nocturnal. These trends are probably due to a variety of causes, such as phylogeny, predation and net avoidance.


As gamboas são canais com traçado meandrante altamente influenciados pelas marés e sofrem grande variação de salinidade e profundidade em um mesmo dia. O objetivo deste trabalho foi comparar as assembléias de peixes diurna e noturna, e para tanto foram escolhidas duas gamboas no sul do Brasil. Coletas mensais foram feitas simultaneamente na maré vazante da tarde e na maré enchente da noite, com o auxílio de redes fyke. Os clupeiformes exibiram tendência para captura diurna. As espécies: Cathorops spixii, Genidens genidens e Rypticus randalli exibiram forte tendência para captura noturna. A família Sciaenidae também mostrou tendência para captura noturna. De forma geral, espécies pelágicas foram mais capturadas durante o dia, e espécies mais relacionadas ao fundo foram mais capturadas à noite, e isto se deve à ação conjunta de vários fatores, tais como: padrões filogenéticos, fuga do instrumento de coleta e busca de locais mais protegidos contra predação.


Subject(s)
Animals , Fishes/classification , Brazil , Circadian Rhythm , Population Dynamics , Seasons
17.
Eur J Biochem ; 268(8): 2351-61, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11298754

ABSTRACT

Large parts of the endoplasmic reticulum of the yeast, Saccharomyces cerevisiae, are located close to intracellular organelles, i.e. mitochondria and the plasma membrane, as shown by fluorescence and electron microscopy. Here we report the isolation and characterization of the subfraction of the endoplasmic reticulum that is closely associated with the plasma membrane. This plasma membrane associated membrane (PAM) is characterized by its high capacity to synthesize phosphatidylserine and phosphatidylinositol. As such, PAM is reminiscent of MAM, a mitochondria associated membrane fraction of the yeast [Gaigg, B., Simbeni, R., Hrastnik, C., Paltauf, F. & Daum, G. (1995) Biochim. Biophys. Acta 1234, 214-220], although the specific activity of phosphatidylserine synthase and phosphatidylinositol synthase in PAM exceeds several-fold the activity in MAM and also in the bulk endoplasmic reticulum. In addition, several enzymes involved in ergosterol biosynthesis, namely squalene synthase (Erg9p), squalene epoxidase (Erg1p) and steroldelta24-methyltransferase (Erg6p), are highly enriched in PAM. A possible role of PAM in the supply of lipids to the plasma membrane is discussed.


Subject(s)
Cell Membrane/metabolism , Endoplasmic Reticulum/metabolism , Lipids/biosynthesis , Saccharomyces cerevisiae/metabolism , Blotting, Western , Ergosterol/biosynthesis , Farnesyl-Diphosphate Farnesyltransferase/metabolism , Green Fluorescent Proteins , Lipid Metabolism , Luminescent Proteins/metabolism , Methyltransferases/metabolism , Microscopy, Electron , Microscopy, Fluorescence , Microsomes/metabolism , Oxygenases/metabolism , Phosphatidylinositols/metabolism , Phosphatidylserines/metabolism , Plasmids/metabolism , Squalene Monooxygenase , Subcellular Fractions/metabolism
18.
Mycotoxin Res ; 17 Suppl 2: 202-5, 2001 Jun.
Article in English | MEDLINE | ID: mdl-23605872

ABSTRACT

Enzyme-linked immunosorbent assays (ELISA) proved to be a fast and simple method for the detection of mycotoxins and other undesired contaminants in food and feed. The present study is focused on the optimisation and exploitation of the egg yolk antibody technology in order to develop competitive ELISAs for the detection of mycotoxins in cereals. Due to its importance as one of the most relevant Fusarium mycotoxins, the trichothecene deoxynivalenol (DON) was selected as representative. Chickens were immunised with different protein conjugates performing varying booster intervals. The antibodies were isolated by the poly(ethylene glycol) precipitation method according to Polson. By use of these antibodies an indirect competitive ELISA was developed for the detection of DON. First investigations of naturally contaminated wheat samples showed a good correspondence with results obtained by GC-ECD when calibration in blank wheat extracts was performed.

19.
Fresenius J Anal Chem ; 367(1): 98-100, 2000 May.
Article in English | MEDLINE | ID: mdl-11227446

ABSTRACT

An indirect competitive enzyme linked immunoassay (ELISA) for the detection of the Fusarium mycotoxin deoxynivalenol (DON) in wheat was developed. Instead of the much more common antibody isolation from mammal serum, DON specific antibodies were, for the first time, isolated from the eggs of previously immunized hens. The limit of detection was 2 microg/L for standard curves and spiked wheat extracts. Recoveries for naturally contaminated samples (200-525 microg/kg) were between 80 and 125% compared with GC-ECD data. Concentrations for naturally contaminated samples were chosen with regard to current Austrian guidelines concerning DON levels in produce intended for human consumption, recommending a maximum of 500 microg DON/kg.


Subject(s)
Antibodies, Fungal/immunology , Egg Yolk/immunology , Enzyme-Linked Immunosorbent Assay/methods , Fusarium/isolation & purification , Trichothecenes/analysis , Triticum/microbiology , Animals , Antibodies, Fungal/biosynthesis , Antibodies, Fungal/isolation & purification , Austria , Chickens/immunology , Female , Food Microbiology/standards , Fusarium/chemistry , Fusarium/immunology , Immunization , Maximum Allowable Concentration , Molecular Structure , Reference Standards , Sensitivity and Specificity , Trichothecenes/immunology , Trichothecenes/toxicity
20.
Mol Biol Cell ; 10(11): 3943-57, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10564282

ABSTRACT

Sterols are major components of the plasma membrane, but their functions in this membrane are not well understood. We isolated a mutant defective in the internalization step of endocytosis in a gene (ERG2) encoding a C-8 sterol isomerase that acts in the late part of the ergosterol biosynthetic pathway. In the absence of Erg2p, yeast cells accumulate sterols structurally different from ergosterol, which is the major sterol in wild-type yeast. To investigate the structural requirements of ergosterol for endocytosis in more detail, several erg mutants (erg2Delta, erg6Delta, and erg2Deltaerg6Delta) were made. Analysis of fluid phase and receptor-mediated endocytosis indicates that changes in the sterol composition lead to a defect in the internalization step. Vesicle formation and fusion along the secretory pathway were not strongly affected in the ergDelta mutants. The severity of the endocytic defect correlates with changes in sterol structure and with the abundance of specific sterols in the ergDelta mutants. Desaturation of the B ring of the sterol molecules is important for the internalization step. A single desaturation at C-8,9 was not sufficient to support internalization at 37 degrees C whereas two double bonds, either at C-5,6 and C-7,8 or at C-5,6 and C-8,9, allowed internalization.


Subject(s)
Endocytosis/genetics , Steroid Isomerases/genetics , Sterols/metabolism , Yeasts/genetics , Carboxypeptidases/metabolism , Cathepsin A , Cloning, Molecular , Ergosterol/biosynthesis , Glycoside Hydrolases/metabolism , Kinetics , Mating Factor , Microscopy, Phase-Contrast , Molecular Structure , Mutation , Peptides/metabolism , Sterols/chemistry , beta-Fructofuranosidase
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