Showing papers by "University of Graz published in 2006"

Hyperelastic modelling of arterial layers with distributed collagen fibre orientations

Abstract: Constitutive relations are fundamental to the solution of problems in continuum mechanics, and are required in the study of, for example, mechanically dominated clinical interventions involving soft biological tissues. Structural continuum constitutive models of arterial layers integrate information about the tissue morphology and therefore allow investigation of the interrelation between structure and function in response to mechanical loading. Collagen fibres are key ingredients in the structure of arteries. In the media (the middle layer of the artery wall) they are arranged in two helically distributed families with a small pitch and very little dispersion in their orientation (i.e. they are aligned quite close to the circumferential direction). By contrast, in the adventitial and intimal layers, the orientation of the collagen fibres is dispersed, as shown by polarized light microscopy of stained arterial tissue. As a result, continuum models that do not account for the dispersion are not able to capture accurately the stress–strain response of these layers. The purpose of this paper, therefore, is to develop a structural continuum framework that is able to represent the dispersion of the collagen fibre orientation. This then allows the development of a new hyperelastic free-energy function that is particularly suited for representing the anisotropic elastic properties of adventitial and intimal layers of arterial walls, and is a generalization of the fibre-reinforced structural model introduced by Holzapfel & Gasser (Holzapfel & Gasser 2001 Comput. Meth. Appl. Mech. Eng. 190, 4379–4403) and Holzapfel et al. (Holzapfel et al. 2000 J. Elast. 61, 1–48). The model incorporates an additional scalar structure parameter that characterizes the dispersed collagen orientation. An efficient finite element implementation of the model is then presented and numerical examples show that the dispersion of the orientation of collagen fibres in the adventitia of human iliac arteries has a significant effect on their mechanical response.

Integrating structured biological data by Kernel Maximum Mean Discrepancy

Abstract: Motivation: Many problems in data integration in bioinformatics can be posed as one common question: Are two sets of observations generated by the same distribution? We propose a kernel-based statistical test for this problem, based on the fact that two distributions are different if and only if there exists at least one function having different expectation on the two distributions. Consequently we use the maximum discrepancy between function means as the basis of a test statistic. The Maximum Mean Discrepancy (MMD) can take advantage of the kernel trick, which allows us to apply it not only to vectors, but strings, sequences, graphs, and other common structured data types arising in molecular biology. Results: We study the practical feasibility of an MMD-based test on three central data integration tasks: Testing cross-platform comparability of microarray data, cancer diagnosis, and data-content based schema matching for two different protein function classification schemas. In all of these experiments, including high-dimensional ones, MMD is very accurate in finding samples that were generated from the same distribution, and outperforms its best competitors. Conclusions: We have defined a novel statistical test of whether two samples are from the same distribution, compatible with both multivariate and structured data, that is fast, easy to implement, and works well, as confirmed by our experiments. Availability: Contact: [email protected]

Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase

Abstract: Fat tissue is the most important energy depot in vertebrates. The release of free fatty acids (FFAs) from stored fat requires the enzymatic activity of lipases. We showed that genetic inactivation of adipose triglyceride lipase (ATGL) in mice increases adipose mass and leads to triacylglycerol deposition in multiple tissues. ATGL-deficient mice accumulated large amounts of lipid in the heart, causing cardiac dysfunction and premature death. Defective cold adaptation indicated that the enzyme provides FFAs to fuel thermogenesis. The reduced availability of ATGL-derived FFAs leads to increased glucose use, increased glucose tolerance, and increased insulin sensitivity. These results indicate that ATGL is rate limiting in the catabolism of cellular fat depots and plays an important role in energy homeostasis.

ERD/ERS patterns reflecting sensorimotor activation and deactivation.

Abstract: Oscillations in the alpha and beta band (<35 Hz) show characteristic spatiotemporal patterns during sensorimotor processing. Whereas event-related desynchronization (ERD) during motor preparation, execution, and imagery can be seen as a correlate of an activated cortical area, event-related synchronization (ERS) of frequency components between 10 and 13 Hz may represent a deactivated cortical area or inhibited cortical network, at least under certain conditions. Induced beta rhythms (13–35 Hz, beta ERS) can be found in sensorimotor areas following both voluntary movement and somatosensory stimulation. In a recent study we used different tasks involving execution and imagery of movements of the upper and lower limb to produce activation vs. deactivation/inhibition of the sensorimotor hand area. Sensorimotor interference, as a function of the activation level of the motor cortex, was studied by the use of repetitive median nerve stimulation (MNS) (ISI 1.5 s) in 12 healthy volunteers during the following task conditions: (i) cube manipulation between thumb and fingers of one hand, (ii) imagined cube manipulation, (iii) continuous foot rotation movements, and (iv) imagined foot movements. EEG was recorded from hand and foot representation areas and processed time-locked to MNS (ERD/ERS). In addition, task-related band power changes (TRPD/TRPI) were analyzed. We found a clear-cut suppression of the stimulation-induced beta ERS (indicating an enhanced activity state of the sensorimotor areas) during active cube manipulation and a weaker suppression during cube imagery. Mental imagination of foot movement led to an increase of the hand area mu rhythm, but did not interfere with stimulation-related effects on beta ERS. These findings support that interfering sensorimotor activation and deactivation is reflected in graduated changes of induced mu and beta oscillations.

How social relations and structures can produce happiness and unhappiness: An international comparative analysis.

Abstract: In this paper, subjective well being, as measured by survey questions on happiness and life satisfaction, is investigated from a sociological-comparative point of view. The central thesis is that happiness and satisfaction must be understood as the outcome of an interaction process between individual characteristics and aspirations on the one side, and social relations and macrosocial structures on the other side. A distinction is made between life satisfaction and happiness; the former is more seen as the outcome of an evaluation process including material and social aspirations and achievements, the latter as an outcome of positive experiences, particularly close personal relationships. The focus of this paper is on micro- and macrosocial conditions favouring or inhibiting the emergence of happiness and satisfaction. It is hypothesized that dense and good basic social relations, occupational involvement and success, sociocultural (religious and altruistic) orientations and participation are conducive to happiness and life satisfaction; the same should be true at the macrolevel for economic prosperity, relatively equal social structures, a well-established welfare state and political democracy. The latter conditions, however, should be more important for life satisfaction than for happiness. A comparative, multilevel regression analysis of happiness in 41 nations around the world is carried out (using the World Value Survey 1995–1997). Both our general assumption and most of the specific hypotheses could be confirmed. It turned very clearly that “happiness” and “life satisfaction” are two different concepts. It could be shown that microsocial embedding and sociocultural integration of a person are highly relevant for happiness. However, contrary to earlier studies, we find that macrosocial factors like the economic wealth of nation, the distribution of income, the extent of the welfare state and political freedom are also relevant, particularly for satisfaction. What counts most is the ability to cope with life, including subjective health and financial satisfaction, close social relations, and the economic perspectives for improvement in the future, both at the level of the individual and at that of the society. These abilities are certainly improved by favourable macrosocial conditions and institutions, such as a more equal income distribution, political democracy and a welfare state.

The impact of microwave synthesis on drug discovery.

Abstract: In the past few years, using microwave energy to heat and drive chemical reactions has become increasingly popular in the medicinal chemistry community. First described 20 years ago, this non-classical heating method has matured from a laboratory curiosity to an established technique that is heavily used in academia and industry. One of the many advantages of using rapid 'microwave flash heating' for chemical synthesis is the dramatic reduction in reaction times--from days and hours to minutes and seconds. As will be discussed here, there are good reasons why many pharmaceutical companies are incorporating microwave chemistry into their drug discovery efforts.

Mutations of the TGF-beta type II receptor BMPR2 in pulmonary arterial hypertension.

Abstract: Pulmonary arterial hypertension (PAH) is clinically characterized by a sustained elevation in mean pulmonary artery pressure leading to significant morbidity and mortality. The disorder is typically sporadic, and in such cases the term idiopathic PAH (IPAH) is used. However, cases that occur within families (familial PAH (FPAH)) display similar clinical and histopathological features, suggesting a common etiology. Heterozygous mutations of a type II member of the TGF-beta cell signaling superfamily known as BMPR2 on chromosome 2q33 have been identified in many kindreds with FPAH, yet display both reduced penetrance and sex bias. This report presents the compilation of data for 144 distinct mutations that alter the coding sequence of the BMPR2 gene identified in 210 independent PAH subjects. This large data set characterizes the extent of sequence variation and reveals that the majority (71%) of mutations in FPAH and IPAH comprise nonsense, frameshift, and splice-site defects, and gene rearrangements. These predict premature termination of the transcript with likely loss through the process of nonsense-mediated decay (NMD). A total of 44 missense mutations were identified that substitute amino acid residues at highly conserved sites within recognized functional domains of the mature receptor. We assess this category of mutations in the context of their heterogeneous effects on cell signaling when assayed by in vitro cell-based systems. Disease-causing mutation hot-spots within BMPR2 are summarized. Taken together, these observations are likely to aid in the development of targeted mutation detection strategies relevant for patient management. Finally, we examine the age- and sex-dependent reduced penetrance of BMPR2 mutations by reviewing bmpr2 animal models and the requirement for additional genetic and/or environmental modifiers of disease. In conclusion, these data provide compelling genetic evidence that haploinsufficiency is the predominant molecular mechanism underlying disease predisposition, and support the concept of a critical threshold of signaling activity below which disease may be precipitated.

A five-gene phylogeny of Pezizomycotina

Abstract: Pezizomycotina is the largest subphylum of Ascomycota and includes the vast majority of filamen- tous, ascoma-producing species. Here we report the results from weighted parsimony, maximum likelihood and Bayesian phylogenetic analyses of five nuclear loci (SSU rDNA, LSU rDNA, RPB1, RPB2 and EF-1a) from 191 taxa. Nine of the 10 Pezizomycotina classes currently recognized were represented in the sam- pling. These data strongly supported the monophyly of Pezizomycotina, Arthoniomycetes, Eurotiomycetes, Orbiliomycetes and Sordariomycetes. Pezizomycetes and Dothideomycetes also were resolved as mono- phyletic but not strongly supported by the data. Lecanoromycetes was resolved as paraphyletic in parsimony analyses but monophyletic in maximum likelihood and Bayesian analyses. Leotiomycetes was polyphyletic due to exclusion of Geoglossaceae. The two most basal classes of Pezizomycotina were Orbilio- mycetes and Pezizomycetes, both of which comprise species that produce apothecial ascomata. The seven

Isolation of quiescent and nonquiescent cells from yeast stationary-phase cultures

Abstract: Quiescence is the most common and, arguably, most poorly understood cell cycle state. This is in part because pure populations of quiescent cells are typically difficult to isolate. We report the isolation and characterization of quiescent and nonquiescent cells from stationary-phase (SP) yeast cultures by density-gradient centrifugation. Quiescent cells are dense, unbudded daughter cells formed after glucose exhaustion. They synchronously reenter the mitotic cell cycle, suggesting that they are in a G0 state. Nonquiescent cells are less dense, heterogeneous, and composed of replicatively older, asynchronous cells that rapidly lose the ability to reproduce. Microscopic and flow cytometric analysis revealed that nonquiescent cells accumulate more reactive oxygen species than quiescent cells, and over 21 d, about half exhibit signs of apoptosis and necrosis. The ability to isolate both quiescent and nonquiescent yeast cells from SP cultures provides a novel, tractable experimental system for studies of quiescence, chronological and replicative aging, apoptosis, and the cell cycle.

Impact of White Matter Hyperintensities Scoring Method on Correlations With Clinical Data The LADIS Study

Abstract: Background and Purpose— White matter hyperintensities (WMH) are associated with decline in cognition, gait, mood, and urinary continence. Associations may depend on the method used for measuring WMH. We investigated the ability of different WMH scoring methods to detect differences in WMH load between groups with and without symptoms. Methods— We used data of 618 independently living elderly with WMH collected in the Leukoaraiosis And DISability (LADIS) study. Subjects with and without symptoms of depression, gait disturbances, urinary incontinence, and memory decline were compared with respect to WMH load measured qualitatively using 3 widely used visual rating scales (Fazekas, Scheltens, and Age-Related White Matter Changes scales) and quantitatively with a semiautomated volumetric technique and an automatic lesion count. Statistical significance between groups was assessed with the χ2 and Mann-Whitney tests. In addition, the punctate and confluent lesion type with comparable WMH volume were compared wi...

Coronary artery stenting and non-cardiac surgery—a prospective outcome study

Abstract: Background A 45% complication rate and a mortality of 20% were reported previously in patients undergoing non-cardiac surgery after coronary artery stenting. Discontinuation of antiplatelet drugs appeared to be of major influence on outcome. Therefore we undertook a prospective, observational multicentre study with predefined heparin therapy and antiplatelet medication in patients undergoing non-cardiac procedures after coronary artery stenting. Methods One hundred and three patients from three medical institutions were enrolled prospectively. Patients received coronary artery stents within 1 yr before non-cardiac surgery (urgent, semi-urgent or elective). Antiplatelet drug therapy was not, or only briefly, interrupted. Heparin was administered to all patients. All patients were on an intensive/intermediate care unit after surgery. Main outcome was the combined (cardiac, bleeding, surgical, sepsis) complication rate. Results Of 103 patients, 44.7% (95% CI 34.9–54.8) suffered complications after surgery; 4.9% (95% CI 1.6–11.0) of the patients died. All but two (bleeding only) adverse events were of cardiac nature. The majority of complications occurred early after surgery. The risk of suffering an event was 2.11-fold greater in patients with recent stents ( Conclusions Despite heparin and despite having all patients on intensive/intermediate care units, cardiac events are the major cause for new perioperative morbidity/mortality in patients undergoing non-cardiac surgery after coronary artery stenting. The complication rate exceeds the re-occlusion rate of stents in patients without surgery (usually

Blood monocytes mimic endothelial progenitor cells.

Abstract: The generation of endothelial progenitor cells (EPCs) from blood monocytes has been propagated as a novel approach in the diagnosis and treatment of cardiovascular diseases. Low-density lipoprotein (LDL) uptake and lectin binding together with endothelial marker expression are commonly used to define these EPCs. Considerable controversy exists regarding their nature, in particular, because myelomonocytic cells share several properties with endothelial cells (ECs). This study was performed to elucidate whether the commonly used endothelial marker determination is sufficient to distinguish supposed EPCs from monocytes. We measured endothelial, hematopoietic, and progenitor cell marker expression of monocytes before and after angiogenic culture by fluorescence microscopy, flow cytometry, and real-time reverse transcription-polymerase chain reaction. The function of primary monocytes and monocyte-derived supposed EPCs was investigated during vascular network formation and EC colony-forming unit (CFU-EC) development. Monocytes cultured for 4 to 6 days under angiogenic conditions lost CD14/CD45 and displayed a commonly accepted EPC phenotype, including LDL uptake and lectin binding, CD31/CD105/CD144 reactivity, and formation of cord-like structures. Strikingly, primary monocytes already expressed most tested endothelial genes and proteins at even higher levels than their supposed EPC progeny. Neither fresh nor cultured monocytes formed vascular networks, but CFU-EC formation was strictly dependent on monocyte presence. LDL uptake, lectin binding, and CD31/CD105/CD144 expression are inherent features of monocytes, making them phenotypically indistinguishable from putative EPCs. Consequently, monocytes and their progeny can phenotypically mimic EPCs in various experimental models.

The specific dermatoses of pregnancy revisited and reclassified: results of a retrospective two-center study on 505 pregnant patients.

Abstract: Objectives We sought to evaluate the frequency and clinical characteristics of pruritic dermatoses in pregnancy and to assess a rationalized classification. Methods Data of 505 pregnant patients seen at two university-based dermatologic hospitals (1994-2004) were retrospectively studied. Results Diagnoses included eczema in pregnancy (49.7%), polymorphic eruption of pregnancy (PEP) (21.6%), pemphigoid gestationis (PG) (4.2%), intrahepatic cholestasis of pregnancy (ICP) (3%), prurigo of pregnancy (0.8%), pruritic folliculitis of pregnancy (0.2%), and miscellaneous dermatoses (20.6%). Eczema in pregnancy, prurigo of pregnancy, and pruritic folliculitis of pregnancy showed considerable overlap and were summarized as atopic eruption of pregnancy (AEP). While PEP, PG, and ICP presented in late pregnancy, AEP started significantly earlier. Primigravidae and multiple gestations were characteristic for PEP, abdominal involvement for PEP and PG, and a history of affected pregnancies for ICP. Limitations This was a retrospective study. Conclusion We propose classifying the dermatoses of pregnancy as PG, PEP, AEP, and ICP. Stereotypic immunofluorescence and laboratory findings are diagnostic of PG and ICP, whereas distinct clinical characteristics facilitate discrimination between PEP and AEP.

New insights into classification and evolution of the Lecanoromycetes (Pezizomycotina, Ascomycota) from phylogenetic analyses of three ribosomal RNA- and two protein-coding genes

Abstract: The Lecanoromycetes includes most of the lichen-forming fungal species (>13 500) and is therefore one of the most diverse class of all Fungi in terms of phenotypic complexity. We report phylogeneti...

Short acting insulin analogues versus regular human insulin in patients with diabetes mellitus.

Abstract: Short acting insulin analogue use for diabetic patients is still controversial, as reflected in many scientific debates. The objective of this review is to assess the effects of short acting insulin analogues versus regular human insulin.

Principles- versus rules-based accounting standards: the FASB's standard setting strategy

Abstract: In response to criticism of rules-based accounting standards and Section 108(d) of the Sarbanes-Oxley Act of 2002, the SEC proposed principles-based (or ‘objectives-oriented’) standards. We identify several shortcomings with this approach and focus on two of them. First, the format (type) of a standard is dependent on the contents of what the standard regulates. Given the asset/liability approach combined with fair values, we argue that the combination of this measurement concept with principles-based standards is inconsistent because it requires significant guidance for management judgment. Second, we propose the inclusion of a true-and-fair override as a necessary requirement for any format that is more than ‘principles-only’ to deal with inconsistencies between principles and guidance. We discuss the benefits of this override and present evidence from the United Kingdom's experience.

Somatic symptoms in depression.

Abstract: Both painful and nonpainful somatic symptoms essentially characterize clinical states of depressive mood. So far, this well-established psychopathological knowledge has been appreciated only insufficiently by the official diagnostic systerms of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, Text Revision (DSM-IV TR) and the ICD-10 Classification of Mental and Behavioral Disorders. Clinical Descriptions and Diagnostic Guidelines (ICD-10). From a perspective of primary care services, this unmet diagnostic need is deplorable, as the main mode of presenting a depression is by reporting somatic symptoms. This somatic form of presentation, however, significantly contributes to low rates of recognition in primary care. A diagnostic challenge may be seen in the differentiation of a depression with prevailing somatic symptoms from anxiety, somatoform disorders, and medical conditions. When somatic symptoms, particularly painful physical conditions, accompany the already debilitating psychiatric and behavioral symptoms of depression, the course of the illness may be more severe, implying a higher risk of early relapse, chronicity, suicide, or mortality due to other natural causes, the economic burden increases considerably the functional status may be hampered heavily, and health-related quality of life may be lowered dramatically. The neurobiological underpinnings of somatic symptoms in depression may guide more promising treatment approaches.

MRI and the diagnosis of multiple sclerosis: expanding the concept of "no better explanation".

Abstract: Although the diagnosis of multiple sclerosis relies on the demonstration of disease dissemination in space and time, the exclusion of other neurological disorders is also essential. The limited specificity of abnormalities disclosed by MRI may increase the likelihood of diagnosis of multiple sclerosis in patients affected by other disorders. The available criteria for diagnosis of multiple sclerosis have not taken advantage of the potential of MRI to detect features "not suggestive" of multiple sclerosis. Recognition of such features in the work-up of patients suspected of having multiple sclerosis may reduce the likelihood of a false positive diagnosis of the disorder in some, while suggesting the correct alternative diagnosis in other patients. On the basis of this, a workshop of the European MAGNIMS (Magnetic Resonance Network in Multiple Sclerosis) was held to define a series of MRI red flags in the setting of clinically suspected multiple sclerosis that is derived from evidence-based findings and educated guesses. The presence of such red flags should alert clinicians to reconsider the differential diagnosis more extensively. In this review we will report on the conclusions of this international consensus, which should represent a first step beyond the concept of "no better explanation", and inform future diagnostic criteria for multiple sclerosis.

An Algorithmic Framework for the Exact Solution of the Prize-Collecting Steiner Tree Problem

Abstract: The Prize-Collecting Steiner Tree Problem (PCST) on a graph with edge costs and vertex profits asks for a subtree minimizing the sum of the total cost of all edges in the subtree plus the total profit of all vertices not contained in the subtree. PCST appears frequently in the design of utility networks where profit generating customers and the network connecting them have to be chosen in the most profitable way. Our main contribution is the formulation and implementation of a branch-and-cut algorithm based on a directed graph model where we combine several state-of-the-art methods previously used for the Steiner tree problem. Our method outperforms the previously published results on the standard benchmark set of problems. We can solve all benchmark instances from the literature to optimality, including some of them for which the optimum was not known. Compared to a recent algorithm by Lucena and Resende, our new method is faster by more than two orders of magnitude. We also introduce a new class of more challenging instances and present computational results for them. Finally, for a set of large-scale real-world instances arising in the design of fiber optic networks, we also obtain optimal solution values.

In Vitro Biofilm Formation of Commensal and Pathogenic Escherichia coli Strains: Impact of Environmental and Genetic Factors

Abstract: Our understanding of Escherichia coli biofilm formation in vitro is based on studies of laboratory K-12 strains grown in standard media. However, pathogenic E. coli isolates differ substantially in their genetic repertoire from E. coli K-12 and are subject to heterogeneous environmental conditions. In this study, in vitro biofilm formation of 331 nondomesticated E. coli strains isolated from healthy (n = 105) and diarrhea-afflicted children (n = 68), bacteremia patients (n = 90), and male patients with urinary tract infections (n = 68) was monitored using a variety of growth conditions and compared to in vitro biofilm formation of prototypic pathogenic and laboratory strains. Our results revealed remarkable variation among the capacities of diverse E. coli isolates to form biofilms in vitro. Notably, we could not identify an association of increased biofilm formation in vitro with a specific strain collection that represented pathogenic E. coli strains. Instead, analysis of biofilm data revealed a significant dependence on growth medium composition (P < 0.05). Poor correlation between biofilm formation in the various media suggests that diverse E. coli isolates respond very differently to changing environmental conditions. The data demonstrate that prevalence and expression of three factors known to strongly promote biofilm formation in E. coli K-12 (F-like conjugative pili, aggregative adherence fimbriae, and curli) cannot adequately account for the increased biofilm formation of nondomesticated E. coli isolates in vitro. This study highlights the complexity of genetic and environmental effectors of the biofilm phenotype within the species E. coli.

Impact of TASK-1 in Human Pulmonary Artery Smooth Muscle Cells

Abstract: The excitability of pulmonary artery smooth muscle cells (PASMC) is regulated by potassium (K+) conductances. Although studies suggest that background K+ currents carried by 2-pore domain K+ channels are important regulators of resting membrane potential in PASMC, their role in human PASMC is unknown. Our study tested the hypothesis that TASK-1 leak K+ channels contribute to the K+ current and resting membrane potential in human PASMC. We used the whole-cell patch-clamp technique and TASK-1 small interfering RNA (siRNA). Noninactivating K+ current performed by TASK-1 K+ channels were identified by current characteristics and inhibition by anandamide and acidosis (pH 6.3), each resulting in significant membrane depolarization. Moreover, we showed that TASK-1 is blocked by moderate hypoxia and activated by treprostinil at clinically relevant concentrations. This is mediated via protein kinase A (PKA)-dependent phosphorylation of TASK-1. To further confirm the role of TASK-1 channels in regulation of resting membrane potential, we knocked down TASK-1 expression using TASK-1 siRNA. The knockdown of TASK-1 was reflected by a significant depolarization of resting membrane potential. Treatment of human PASMC with TASK-1 siRNA resulted in loss of sensitivity to anandamide, acidosis, alkalosis, hypoxia, and treprostinil. These results suggest that (1) TASK-1 is expressed in human PASMC; (2) TASK-1 is hypoxia-sensitive and controls the resting membrane potential, thus implicating an important role for TASK-1 K+ channels in the regulation of pulmonary vascular tone; and (3) treprostinil activates TASK-1 at clinically relevant concentrations via PKA, which might represent an important mechanism underlying the vasorelaxing properties of prostanoids and their beneficial effect in vivo.

Cubic membranes: a legend beyond the Flatland* of cell membrane organization

Abstract: Cubic membranes represent highly curved, three-dimensional nanoperiodic structures that correspond to mathematically well defined triply periodic minimal surfaces. Although they have been observed in numerous cell types and under different conditions, particularly in stressed, diseased, or virally infected cells, knowledge about the formation and function of nonlamellar, cubic structures in biological systems is scarce, and research so far is restricted to the descriptive level. We show that the “organized smooth endoplasmic reticulum” (OSER; Snapp, E.L., R.S. Hegde, M. Francolini, F. Lombardo, S. Colombo, E. Pedrazzini, N. Borgese, and J. Lippincott-Schwartz. 2003. J. Cell Biol. 163:257–269), which is formed in response to elevated levels of specific membrane-resident proteins, is actually the two-dimensional representation of two subtypes of cubic membrane morphology. Controlled OSER induction may thus provide, for the first time, a valuable tool to study cubic membrane formation and function at the molecular level.