1. |
- van der Oost, John, et al.
(author)
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Bacillus subtilis cytochrome oxidase mutants: biochemical analysis and genetic evidence for two aa3-type oxidases
- 1991
-
In: Molecular Microbiology. - : Wiley. - 1365-2958 .- 0950-382X. ; 5:8, s. 2063-2072
-
Journal article (peer-reviewed)abstract
- The ctaBCDEF genes coding for cytochrome c oxidase were found to reside adjacent to a regulatory gene ctaA at 127-degrees on the Bacillus subtilis chromosome. The structural genes for subunits I and II, ctaD and ctaC, were deleted by gene-replacement using a phleomycin-resistance marker. The mutant was unable to oxidize N,N,N',N'-tetramethyl-p-phenylenediamine and oxidized cytochrome c at a significantly lower rate. Absorption spectra of the mutant and wild-type membranes confirmed the presence of two haem A-containing enzymes in B. subtilis. Another mutant, with a spontaneous deletion upstream from ctaC, was found to express neither of these enzymes. Radioactive haem-labelling was used to identify subunit 11, which contains a haem C, and cytochrome c-550 among the membrane-bound c-type cytochromes of B. subtilis.
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2. |
- Axelson, H, et al.
(author)
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A new variant 15; 16 translocation in mouse plasmacytoma leads to the juxtaposition of c-myc and immunoglobulin lambda
- 1991
-
In: Oncogene. - 0950-9232. ; 6:12, s. 70-2263
-
Journal article (peer-reviewed)abstract
- Mouse plasmacytomas (MPCs) induced by pristane oil, or by a combination of pristane oil and Abelson virus, carry one of two chromosomal translocations. The typical 12; 15 translocation leads to the juxtaposition of c-myc and immunoglobulin heavy-chain sequences, whereas the 6; 15 translocation links the kappa light-chain locus with the pvt-1 (plasmacytoma variant translocation) locus, located at least 75kb 3' of c-myc [Cory, S., Graham, M., Webb, E., Corcoran, L. & Adams, J. (1985). EMBO J., 4, 675-681]. Unlike the human Burkitt's lymphoma-associated translocation, the lambda/myc juxtaposed variant translocation has not been found previously in MPCs. Using unconventional MPC induction systems in which the tumor precursor cell was induced to proliferate in a secondary host, we have recently identified a 15; 16 translocation in six of the derived MPCs [Wiener, F., Silva, S., Sugiyama, H., Babonits, M. & Klein, G. (1990). Genes Chromosomes Cancer, 2, 36-43]. Chromosome 16 harbors the lambda light-chain gene. To explore whether the 15; 16 translocation represents the lambda/myc juxtaposition, we have mapped the breakpoints on chromosomes 15 and 16 by pulsed-field gel electrophoresis (PFGE). The pvt-1 region was mapped to approximately 220 kb 3' of c-myc. The breakpoint on chromosome 15 in ABPC-Ch-163-10, one of the six 15; 16 translocation-carrying MPCs, was situated approximately 80 kb 3' of c-myc and 140 kb 5' of pvt-1b, the major breakpoint cluster region of the previously analysed 6; 15 variant MPCs. The breakpoint on chromosome 16 was found to cut between the V1 and C3 regions of the lambda locus. Co-migration experiments showed that the C3 and the myc gene were juxtaposed head to tail on the 15; 16 translocation chromosome. On the reciprocal product V1 was juxtaposed to pvt-1.
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3. |
- Bengtsson, Henrik, et al.
(author)
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A population based screening of abdominal aortic aneurysms (AAA)
- 1991
-
In: European Journal of Vascular Surgery. - 0950-821X. ; 5:1, s. 53-57
-
Journal article (peer-reviewed)abstract
- The prevalence of abdominal aortic aneurysm (AAA) in a defined population of elderly men and its correlation to some risk factors were studied in the population cohort "men born in 1914 from Malmo". A total of 499 were invited to attend and 375 (75%) did so. The aorta could be visualised with ultrasound in 364 patients, 39 (10.7%) of whom had aneurysmal changes. The presence of an AAA was related to the findings at a general health examination undertaken 5 years previously. Tobacco and alcohol consumption, impaired lung function and a history of angina pectoris were related to the presence of an AAA. No relationship was found between an AAA and hypertension, hyperlipidaemia or hyperglycaemia. A decreased tissue elasticity as a common denominator for the lung function impairment and development of AAA is discussed.
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4. |
- Hughes, Diarmaid, 1956-
(author)
-
Error-prone EF-Tu reduces in vivo enzyme activity and cellular growth rate
- 1991
-
In: Molecular Microbiology. - 0950-382X .- 1365-2958. ; 5:3, s. 623-630
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Journal article (peer-reviewed)abstract
- Mutations in Salmonella typhimurium encoding error-prone EF-Tu (tufA8, tufB103) enhance translational error levels and also cause a reduced growth rate. The relative changes in error level and growth rate are inversely related and dependent on the status of the two tuf genes. Possible causes of the reduced growth rate were investigated. Several important parameters with the potential to alter growth rate (the EF-Tu-ribosome interaction, the in vivo elongation rate and the processivity of translation), are all relatively unaffected by the tuf mutations. The small reduction in processivity observed in some strains is not quantitatively related to the growth rate reduction. Instead, the error-enhancing mutations are associated with a large reduction in the specific activity of a test protein, β-galactosidase, suggesting by inference that the reduced growth rate is a consequence of the synthesis of error-containing proteins.
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5. |
- Lundgren, Birgit, et al.
(author)
-
Extruded wheat flour: Flavour and texture-comparison of evaluations by two laboratories
- 1991
-
In: Food Quality and Preference. - 0950-3293 .- 1873-6343. ; 3:1, s. 1-12
-
Journal article (peer-reviewed)abstract
- Intensities of flavour and texture attributes of 23 extruded wheat flour samples were evaluated by two laboratory panels in Sweden and in the UK. For most attributes good agreement between the two panels was obtained. Discrepancies were considered to be caused by inadequate definition of the terms. © 1992.
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6. |
- Andersson, Hanna, 1991-, et al.
(author)
-
Anchoring effect in judgments of objective fact and subjective preference
- 2021
-
In: Food Quality and Preference. - : Elsevier. - 0950-3293 .- 1873-6343. ; 88
-
Journal article (peer-reviewed)abstract
- The way by which various sources of external information interact in their effects on judgment is rarely investigated. Here, we report two experiments that examine how two sources of external information—an anchor (a reference price) and an eco-label—influence judgments of an objective fact (product price) and a subjective preference (willingness-to-pay for the product). Participants’ price judgments were drawn in the direction of the anchor point, whereas the eco-label resulted in higher judgments of objective fact (Experiment 1) but did not influence subjective preference (Experiment 2). Interestingly, the eco-label seemed to strengthen the effect of the high anchor in judgments of objective fact. Further, participants with higher environmental concern answered a higher price on the subjective preference questions when they received a high anchor, as well as a lower price when they received a low anchor in comparison to the low environmental concern group. This study demonstrates that various external information sources can strengthen each other’s effects on consumer belief about products, while the effects are weaker for consumers’ preferences. The implications of the results for decision making are discussed.
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7. |
- Podraza-Farhanieh, Agnieszka, 1991, et al.
(author)
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A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.
- 2023
-
In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 150:6
-
Journal article (peer-reviewed)abstract
- Neuropeptides, including insulin, are important regulators of physiological functions of the organisms. Trafficking through the Golgi is crucial for the regulation of secretion of insulin-like peptides. ASNA-1 (TRC40) and ENPL-1 (GRP94) are conserved insulin secretion regulators in Caenorhabditis elegans (and mammals), and mouse Grp94 mutants display type 2 diabetes. ENPL-1/GRP94 binds proinsulin and regulates proinsulin levels in C. elegans and mammalian cells. Here, we have found that ASNA-1 and ENPL-1 cooperate to regulate insulin secretion in worms via a physical interaction that is independent of the insulin-binding site of ENPL-1. The interaction occurs in DAF-28/insulin-expressing neurons and is sensitive to changes in DAF-28 pro-peptide levels. Consistently, ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The chaperone form of ASNA-1 was likely the interaction partner of ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization to the Golgi was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed the ASNA-1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 that is necessary to maintain proper insulin secretion in C. elegans and provides insights into how their loss might cause diabetes in mammals.
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8. |
- Wang, Y. J., et al.
(author)
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Cyclic AMP in oocytes controls meiotic prophase I and primordial folliculogenesis in the perinatal mouse ovary
- 2015
-
In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 142:2, s. 343-351
-
Journal article (peer-reviewed)abstract
- In mammalian ovaries, a fixed population of primordial follicles forms during the perinatal stage and the oocytes contained within are arrested at the dictyate stage of meiotic prophase I. In the current study, we provide evidence that the level of cyclic AMP ( cAMP) in oocytes regulates oocyte meiotic prophase I and primordial folliculogenesis in the perinatal mouse ovary. Our results show that the early meiotic development of oocytes is closely correlated with increased levels of intra-oocyte cAMP. Inhibiting cAMP synthesis in fetal ovaries delayed oocyte meiotic progression and inhibited the disassembly and degradation of synaptonemal complex protein 1. In addition, inhibiting cAMP synthesis in in vitro cultured fetal ovaries prevented primordial follicle formation. Finally, using an in situ oocyte chromosome analysis approach, we found that the dictyate arrest of oocytes is essential for primordial follicle formation under physiological conditions. Taken together, these results suggest a role for cAMP in early meiotic development and primordial follicle formation in the mouse ovary.
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9. |
- Wolfstetter, Georg, et al.
(author)
-
Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system patterning
- 2019
-
In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 146:2
-
Journal article (peer-reviewed)abstract
- Basement membranes (BMs) are specialized layers of extracellular matrix (ECM) mainly composed of Laminin, type IV Collagen, Perlecan and Nidogen/entactin (NDG). Recent in vivo studies challenged the initially proposed role of NDG as a major ECM linker molecule by revealing dispensability for viability and BM formation. Here, we report the characterization of the single Ndg gene in Drosophila. Embryonic Ndg expression was primarily observed in mesodermal tissues and the chordotonal organs, whereas NDG protein localized to all BMs. Although loss of Laminin strongly affected BM localization of NDG, Ndg-null mutants exhibited no overt changes in the distribution of BM components. Although Drosophila Ndg mutants were viable, loss of NDGled to ultrastructural BM defects that compromised barrier function and stability in vivo. Moreover, loss of NDG impaired larval crawling behavior and reduced responses to vibrational stimuli. Further morphological analysis revealed accompanying defects in the larval peripheral nervous system, especially in the chordotonal organs and the neuromuscular junction (NMJ). Taken together, our analysis suggests that NDG is not essential for BM assembly but mediates BM stability and ECM-dependent neural plasticity during Drosophila development.
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10. |
- Galozy, Alexander, 1991-, et al.
(author)
-
Information-gathering in latent bandits
- 2023
-
In: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 260
-
Journal article (peer-reviewed)abstract
- In the latent bandit problem, the learner has access to reward distributions and – for the non-stationary variant – transition models of the environment. The reward distributions are conditioned on the arm and unknown latent states. The goal is to use the reward history to identify the latent state, allowing for the optimal choice of arms in the future. The latent bandit setting lends itself to many practical applications, such as recommender and decision support systems, where rich data allows the offline estimation of environment models with online learning remaining a critical component. Previous solutions in this setting always choose the highest reward arm according to the agent’s beliefs about the state, not explicitly considering the value of information-gathering arms. Such information-gathering arms do not necessarily provide the highest reward, thus may never be chosen by an agent that chooses the highest reward arms at all times.In this paper, we present a method for information-gathering in latent bandits. Given particular reward structures and transition matrices, we show that choosing the best arm given the agent’s beliefs about the states incurs higher regret. Furthermore, we show that by choosing arms carefully, we obtain an improved estimation of the state distribution, and thus lower the cumulative regret through better arm choices in the future. Through theoretical analysis we show that the proposed method retains the sub-linear regret rate of previous methods while having much better problem dependent constants. We evaluate our method on both synthetic and real-world data sets, showing significant improvement in regret over state-of-the-art methods. © 2022 The Author(s).
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11. |
- Hansson, Josef, 1991, et al.
(author)
-
Novel nanostructured thermal interface materials: a review
- 2018
-
In: International Materials Reviews. - : Informa UK Limited. - 0950-6608 .- 1743-2804. ; 63:1, s. 22-45
-
Research review (peer-reviewed)abstract
- The trend of continuing miniaturisation of microelectronics leads to new thermal management challenges. A key point in the heat removal process development is to improve the heat conduction across interfaces through improved thermal interface materials (TIMs). We identify the key areas for state-of-the art TIM research and investigate the current state of the field together with possible future advances.
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12. |
- Henriksson, Jens, 1991, et al.
(author)
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Performance analysis of out-of-distribution detection on trained neural networks
- 2020
-
In: Information and Software Technology. - : Elsevier B.V.. - 0950-5849 .- 1873-6025.
-
Journal article (peer-reviewed)abstract
- Context: Deep Neural Networks (DNN) have shown great promise in various domains, for example to support pattern recognition in medical imagery. However, DNNs need to be tested for robustness before being deployed in safety critical applications. One common challenge occurs when the model is exposed to data samples outside of the training data domain, which can yield to outputs with high confidence despite no prior knowledge of the given input. Objective: The aim of this paper is to investigate how the performance of detecting out-of-distribution (OOD) samples changes for outlier detection methods (e.g., supervisors) when DNNs become better on training samples. Method: Supervisors are components aiming at detecting out-of-distribution samples for a DNN. The experimental setup in this work compares the performance of supervisors using metrics and datasets that reflect the most common setups in related works. Four different DNNs with three different supervisors are compared during different stages of training, to detect at what point during training the performance of the supervisors begins to deteriorate. Results: Found that the outlier detection performance of the supervisors increased as the accuracy of the underlying DNN improved. However, all supervisors showed a large variation in performance, even for variations of network parameters that marginally changed the model accuracy. The results showed that understanding the relationship between training results and supervisor performance is crucial to improve a model's robustness. Conclusion: Analyzing DNNs for robustness is a challenging task. Results showed that variations in model parameters that have small variations on model predictions can have a large impact on the out-of-distribution detection performance. This kind of behavior needs to be addressed when DNNs are part of a safety critical application and hence, the necessary safety argumentation for such systems need be structured accordingly.
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13. |
- Wang, Shunfeng, 1991, et al.
(author)
-
Co-utilization of quarry tailings and fly ash for non-sintered ultra-lightweight aggregates (ULWAs) by autoclave technology
- 2022
-
In: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 346
-
Journal article (peer-reviewed)abstract
- Quarry tailings as solid waste with large output bring a heavy environmental and economic burden. The main objective of this study is to investigate the feasibility of co-utilizing quarry tailings and fly ash (FA) as the main sources in preparing the lightweight aggregates (LWAs). The expand perlite powder (characterized with low density and high surface area) and two chemical foaming agents (ammonium carbonate and Al powder) was added to reduce the density of LWAs furtherly and fabricate a type of ultra-lightweight aggregates (ULWAs) through autoclave curing. In spite of the basic properties (compressive strength, 1 h of water absorption, loose bulk density and apparent particle density), the evolution of pore structures in relation to the type of foaming agents were also determined by combining scanning electron microscope (SEM), mercury intrusion porosimetry (MIP) and Nuclear Magnetic Resonance (NMR). The results show that increasing the expand perlite content could increases the compressive strength and water absorption, decreases the loose bulk density, apparent density and the total porosity. The pores wall gradually reduces with the increase of chemical foaming agents. Isolated pores will transform into connected pores, which also increase the most probable pore diameter and total porosity. The loose bulk density of specimens with 3 wt% (NH4)2CO3 and Al powder are 873 kg/m3 and 798 kg/m3 compared to blank (1132 kg/m3). This work lays a solid foundation for the design and preparation of ULWAs from solid wastes.
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14. |
- Wang, Shunfeng, 1991, et al.
(author)
-
Resourceful utilization of quarry tailings in the preparation of non-sintered high-strength lightweight aggregates
- 2022
-
In: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 334
-
Journal article (peer-reviewed)abstract
- Quarry tailings are usually stockpiled due to stable crystalline structures below 100 °C and abundant sources, which lead to a serious environmental impacts and high ecological risks. This paper presents a study of transforming the fly ash and quarry tailings as the main raw materials into lightweight aggregates (LWAs) for using in civil engineering. A novel curing regime (autoclave technology) has been proposed to obtain higher compressive strength of LWAs. The effects of curing parameters (including temperature and steam pressure) on the properties (compressive strength, water absorption, loose bulk density, phase composition, pore structure and microstructure) of LWAs were systematically evaluated. On the other hand, this research also studies the effect of cement content on the basic properties of LWAs, which was decreased from 30 to 10 wt% for declining the CO2 emission. Results show that the strength sharply increases from 2.48 to 11.95 MPa and the water absorption decreases from 11.2 to 2.09% with increasing the elevated curing temperature from 25 to 190 °C. The LWA prepared with 70 wt% solid wastes (fly ash and quarry tailings) at 190 °C achieved the highest strength (11.95 MPa) and the lower loose bulk density (1160 kg/m3), which could meet the requirement of Chinese LWAs standard (GB/T 17431.1-2010). The water absorption of LWAs is below 5% except sample T25. The total porosity of LWAs decreases from 39.65% to 26.32% at 150 °C and from 42.54% to 27.24% at 190 °C while the cement content increases form 10 wt% to 30 wt%. At the same time, the percentage of pores (>50 nm) also gradually decreases. While the curing temperature, pressure and cement usage are above 150 °C, 1.00 MPa and 10 wt% respectively, will promote the formation of new phase composition (analcime). That also further increases the strength and percentage of harmless pores and few harmful pores. Therefore, this research offers a new curing method for producing LWAs from 70 to 90 wt% solid waste and is a rapid and sustainable solution for the large-scale recycling of quarry tailings.
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15. |
- Wang, Shunfeng, 1991, et al.
(author)
-
The toxic leaching behavior of MSWI fly ash made green and non-sintered lightweight aggregates
- 2023
-
In: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 373
-
Journal article (peer-reviewed)abstract
- With the rapid development of urbanization and the economy, the amount of municipal solid waste incineration fly ash (MSWI fly ash) dramatically increases and stacks up. Declining the leaching concentration of hazardous heavy metals in municipal solid waste incineration fly ash and enlarging the application range in wastewater and biosorption of non-sintered LWAs have always got more attention from more and more researchers. Green and non-sintered LWAs were prepared by using the waste solids (MSWI fly ash and coal fly ash) as raw materials through autoclave technology. In the meantime, the effect of severe leaching environment (pH = 1, 3, 5 and 7) on the stabilization of heavy metals in the LWAs with MSWI fly ash and extra heavy metals were systematically investigated by means of Inductively Coupled Plasma Optical Emission Spectrometer, X-ray diffraction, Fourier Transform Infrared Spectrometer, X-ray photoelectron spectra and Scanning electron microscope. The results revealed that the heavy metals are well immobilized in the LWA matrix through physical encapsulation and adsorption by hydration products (C-S-H). The leaching rate (LR) and cumulative leaching rate (CLR) of heavy metals, phase compositions and chemical structures in LWAs with heavy metals at pH of 1 are significantly changed, but the cumulative leaching rate of Pb2+ is lower than that of Zn2+ and Cu2+. The structure of hydration products in the matrix will be broken and reformed to gypsum under an acid environment (pH = 1). The leaching rate and cumulative leaching rate of heavy metals in LWAs with heavy metals under various leaching environments are much lower when the pH is above 1, which could meet the leaching requirement. This research could provide theoretical support for the application of non-sintered and municipal solid waste incineration fly ash based LWAs in concrete.
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16. |
- Mason, Elliot C., 1991-
(author)
-
Phillis Wheatley Peters’ fugitive poetics of freedom
- 2023
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In: Textual Practice. - : Routledge. - 0950-236X .- 1470-1308. ; 37:12, s. 1912-1931
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Journal article (peer-reviewed)abstract
- The enslaved eighteenth-century poet Phillis Wheatley Peters has often beenunderstood as a mimetic mouthpiece for her white enslavers. Here, throughclose readings of her poetry and letters, I understand her work through thefugitive imaginings of freedom in contemporary Black studies scholarship,finding in her complex poetics textual catachresis and irony that elude theunderstanding of her audience. Through subtle references to an alternativeAfrican past, subsumed in the American regime of slavery and yet ongoing ina fugitive poetic imaginary, Wheatley Peters constructs a way out of herenslavement without reference to the future, but rather to the opening of analternative past. Living during the US Revolutionary War, in a period ofintense belief in the political establishment of an ideal future, WheatleyPeters’ability toflee into a catachrestic past constitutes a radical movementagainst the homogenising operation of America’s foundation. TracingWheatley Peters’ movements through Fred Moten, Saidiya Hartman, andAlexander Weheliye as pushing beyond the limitations of freedom astheorised by Jean-Luc Nancy, I define Wheatley Peters’ poetics as ‘freedom from Freedom’. This essay redefines the very beginning of Black Americanliterature through a poetic philosophy of freedom from Freedom.
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17. |
- Alhede, Andreas, 1996, et al.
(author)
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A two-stage study of steel corrosion and internal cracking revealed by multimodal tomography
- 2023
-
In: Construction and Building Materials. - 0950-0618. ; 394
-
Journal article (peer-reviewed)abstract
- Modeling of corrosion-induced cracking is limited by lacking knowledge on the behavior of corrosion products. In this work, the corrosion and cracking processes were experimentally investigated in 3D at two different stages. The processes were measured at micro-structural scale, applying nondestructive neutron and X-ray computed tomography in two scans at different stages in the corrosion process. A method to evaluate the average volumetric strain of the compressed corrosion layer was proposed and displacements in the concrete matrix were measured. Strain localization revealed cracks not directly visible in the images. Multimodal tomography demonstrated to be an effective method for investigating steel corrosion in reinforced concrete.
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18. |
- Deshmukh, Shradha, et al.
(author)
-
Explainable quantum clustering method to model medical data
- 2023
-
In: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 267, s. 1-13
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Journal article (peer-reviewed)abstract
- Medical experts are often skeptical of data-driven models due to the lack of their explainability. Several experimental studies commence with wide-ranging unsupervised learning and precisely with clustering to obtain existing patterns without prior knowledge of newly acquired data. Explainable Artificial Intelligence (XAI) increases the trust between virtual assistance by Machine Learning models and medical experts. Awareness about how data is analyzed and what factors are considered during the decision-making process can be confidently answered with the help of XAI. In this paper, we introduce an improved hybrid classical-quantum clustering (improved qk-means algorithm) approach with the additional explainable method. The proposed model uses learning strategies such as the Local Interpretable Model-agnostic Explanations (LIME) method and improved quantum k-means (qk-means) algorithm to diagnose abnormal activities based on breast cancer images and Knee Magnetic Resonance Imaging (MRI) datasets to generate an explanation of the predictions. Compared with existing algorithms, the clustering accuracy of the generated clusters increases trust in the model-generated explanations. In practice, the experiment uses 600 breast cancer (BC) patient records with seven features and 510 knee MRI records with five features. The result shows that the improved hybrid approach outperforms the classical one in the BC and Knee MRI datasets. © 2023 Elsevier B.V.
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19. |
- Guo, Xiaoyi, et al.
(author)
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Subspace projection-based weighted echo state networks for predicting therapeutic peptides
- 2023
-
In: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 263
-
Journal article (peer-reviewed)abstract
- Detection of therapeutic peptide is a major research direction in the current biopharmaceutical field. However, traditional biochemical experimental detection methods take a lot of time. As supplementary methods for biochemical experiments, the computational methods can improve the efficiency of therapeutic peptide detection. Currently, most machine learning-based therapeutic peptide identification algorithms do not consider the processing of noisy samples. We propose a therapeutic peptide classifier, called weighted echo state networks based on subspace projection (WESN-SP), which reduces the bias caused by high-dimensional noisy features and noisy samples. WESN-SP is trained by sparse Bayesian learning algorithm (SBL) and introduces a weight coefficient for each sample by kernel dependence maximization-based subspace projection. The experimental results show that WESN-SP has better performance than other existing methods. © 2023 The Author(s). Published by Elsevier B.V.
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20. |
- Huang, Liming, 1993, et al.
(author)
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Influence of calcination temperature on the structure and hydration of MgO
- 2020
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In: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 262
-
Journal article (peer-reviewed)abstract
- The performance of magnesium oxide-based cements and expansion agent closely relates to the reactivity of MgO. This paper systematically investigates the structure and hydration properties of MgO calcined from amorphous magnesite at a wide range of temperatures from 400 to 1150 ℃. XRD, SEM, BET and PSD tests were carried out to determine the structure and particle properties of MgO. The hydration reactivity of MgO was indexed with isothermal calorimeter, DTG, XRD and TEM test. Increasing temperature augments the crystallinity and size of MgO nanograins from about 23.85 nm to 86.37 nm, decreases the specific surface area but makes the particles agglomerate into smaller size. The increasing temperature prolongs the induction period and retards the hydration rate of main peak. The total cumulative heat from complete hydration of MgO is with a similar value of about 800 J/g. The hydration reactivity of MgO can be accurately indexed by its heat release. MgO calcined at 700 ℃ has high reactivity and it dissolves quickly leading to the precipitation of needle Mg(OH)2 initially. The needle brucite has poor crystallinity but it transforms into flake and clavate shape. MgO calcined at 1150 ℃ has very low dissolving rate. The dissolution starts from the (1 1 0) truncation at <1 0 0> edges, and then the cuts at (1 1 1) occur to create an octahedron shape. Some clavate brucite initially precipitates instead of needle brucite during the hydration of low reactive MgO.
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21. |
- Li, Ping, et al.
(author)
-
Sparse regularized joint projection model for identifying associations of non-coding RNAs and human diseases
- 2022
-
In: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 258
-
Journal article (peer-reviewed)abstract
- Current human biomedical research shows that human diseases are closely related to non-coding RNAs, so it is of great significance for human medicine to study the relationship between diseases and non-coding RNAs. Current research has found associations between non-coding RNAs and human diseases through a variety of effective methods, but most of the methods are complex and targeted at a single RNA or disease. Therefore, we urgently need an effective and simple method to discover the associations between non-coding RNAs and human diseases. In this paper, we propose a sparse regularized joint projection model (SRJP) to identify the associations between non-coding RNAs and diseases. First, we extract information through a series of ncRNA similarity matrices and disease similarity matrices and assign average weights to the similarity matrices of the two sides. Then we decompose the similarity matrices of the two spaces into low-rank matrices and put them into SRJP. In SRJP, we innovatively use the projection matrix to combine the ncRNA side and the disease side to identify the associations between ncRNAs and diseases. Finally, the regularization term in SRJP effectively improves the robustness and generalization ability of the model. We test our model on different datasets involving three types of ncRNAs: circRNA, microRNA and long non-coding RNA. The experimental results show that SRJP has superior ability to identify and predict the associations between ncRNAs and diseases. © 2022 The Author(s)
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22. |
- Li, Zhen, et al.
(author)
-
Using alumina-rich sludge and phosphogypsum manufactures low-CO 2 cement
- 2021
-
In: Construction and Building Materials. - : Elsevier BV. - 0950-0618. ; 288
-
Journal article (peer-reviewed)abstract
- Calcium sulfoaluminate-belite (CŜAB) cement has been proposed as a low-CO cement for substituting ordinary Portland cement (OPC). The aim of this work was to study synthesis of CŜAB cement from two industrial wastes, namely Alumina-rich sludge (AS) and phosphogypsum (PG). The main phases of the synthesized cement were ye'elimite, larnite, ternesite and anhydrite. The properties of CŜAB cement were investigated through the test of compressive strength, setting time and hydration products. We found that the optimal procedure was burning at 1150 °C for 1 h which needs much lower energy than traditional production. CŜAB cement could reach 39.4 MPa at 28 d hydration, when basicity factor, the ratio of aluminum to sulfur and aluminum to silicon ratio were 0.8, 2.5 and 3 respectively. Blending phosphogypsum into clinker, made paste get a much higher compressive strength (53.2 MPa at 28 d). Adding phosphogypsum to CŜAB cement hindered hydration process of cement and decreased hydration products except for ettringite. Production of this cement is beneficial to recycle industrial wastes and reduce CO emission. This is meaningful for further development of cement industry. 2 2
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23. |
- Liu, Dongyun, et al.
(author)
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A review of concrete properties under the combined effect of fatigue and corrosion from a material perspective
- 2023
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In: Construction and Building Materials. - : Elsevier. - 0950-0618 .- 1879-0526. ; 369
-
Research review (peer-reviewed)abstract
- When in use, reinforced concrete bridge structures not only experience high-frequency fatigue loading caused by passing vehicles, but also suffer from the effects of a corrosive environment. In addition to fatigue damage to reinforcement, long-term fatigue loading also causes concrete cracking and deterioration of pore structures, thereby accelerating the ingress of external corrosive substances and reducing concrete durability. Long-term exposure to a corrosive environment also reduces the performance of concrete and causes corrosion of reinforcement materials, affecting the fatigue performance of the structure. Therefore, there is a combined effect between fatigue loads and corrosion on concrete. This paper is a review of the current literature from a material perspective on the performance degradation of concrete under the combined action of fatigue loading and corrosion, that is, carbonation, chloride ion attack, freeze–thaw cycles, and sulphate attack. The paper includes (1) a description of a test method for examining the combined action of fatigue loading and corrosion, (2) a summary of performance degradation of concrete under the combined effect of fatigue loading and corrosion, and (3) an introduction to durability deterioration models considering fatigue damage, and fatigue models that can account for corrosion. Finally, potential future research on concrete under the combined effect of fatigue loading and corrosion is described.
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24. |
- Liu, Junkai, et al.
(author)
-
AMDGT : Attention aware multi-modal fusion using a dual graph transformer for drug–disease associations prediction
- 2024
-
In: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 284
-
Journal article (peer-reviewed)abstract
- Identification of new indications for existing drugs is crucial through the various stages of drug discovery. Computational methods are valuable in establishing meaningful associations between drugs and diseases. However, most methods predict the drug–disease associations based solely on similarity data, neglecting valuable biological and chemical information. These methods often use basic concatenation to integrate information from different modalities, limiting their ability to capture features from a comprehensive and in-depth perspective. Therefore, a novel multimodal framework called AMDGT was proposed to predict new drug associations based on dual-graph transformer modules. By combining similarity data and complex biochemical information, AMDGT understands the multimodal feature fusion of drugs and diseases effectively and comprehensively with an attention-aware modality interaction architecture. Extensive experimental results indicate that AMDGT surpasses state-of-the-art methods in real-world datasets. Moreover, case and molecular docking studies demonstrated that AMDGT is an effective tool for drug repositioning. Our code is available at GitHub: https://github.com/JK-Liu7/AMDGT. © 2023 The Author(s)
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25. |
- Min, Xinzhe, et al.
(author)
-
A nonlinear prediction model of the debonding process of an FRP-concrete interface under fatigue loading
- 2023
-
In: Construction and Building Materials. - : Elsevier Ltd. - 0950-0618 .- 1879-0526. ; 369
-
Journal article (peer-reviewed)abstract
- Externally bonded Fiber Reinforced Polymer (FRP) strengthening has been proven to be an efficient and reliable method for structural strengthening of reinforced concrete (RC) members. However, the beneficial effects of this method can be diminished due to the debonding of the FRP laminates. The mechanism of FRP debonding still requires further research, especially for strengthened members under fatigue loading. To understand and predict the FRP fatigue debonding process better, eleven FRP-concrete joint specimens were tested under static or fatigue loading. Both the theoretical derivation and the experimental study indicated that the debonding growth rate of the FRP laminate depended not only on the mean level (), but also the amplitude () of the applied fatigue load. In addition, the debonded portion of the FRP laminate had a significant impact on the following debonding process due to the friction and mechanical interaction between the debonded FRP and the concrete surface. Therefore, a new nonlinear prediction model is proposed in this paper. The proposed model explicitly took into account the amplitude and the mean level of the fatigue loading, which enabled the effect of both to be modelled. Meanwhile, a correction term was also introduced into the model to account for the influence of the previously debonded FRP laminate. The predicted results of the debonding growth rate and the debonding length agreed well with the experimental results.
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26. |
- Rani, Sita, et al.
(author)
-
Federated learning for secure IoMT-applications in smart healthcare systems : A comprehensive review
- 2023
-
In: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 274
-
Research review (peer-reviewed)abstract
- Recent developments in the Internet of Things (IoT) and various communication technologies have reshaped numerous application areas. Nowadays, IoT is assimilated into various medical devices and equipment, leading to the progression of the Internet of Medical Things (IoMT). Therefore, various IoMT-based healthcare applications are deployed and used in the day-to-day scenario. Traditionally, machine learning (ML) models use centralized data compilation and learning that is impractical in pragmatic healthcare frameworks due to rising privacy and data security issues. Federated Learning (FL) has been observed as a developing distributed collective paradigm, the most appropriate for modern healthcare framework, that manages various stakeholders (e.g., patients, hospitals, laboratories, etc.) to carry out training of the models without the actual exchange of sensitive medical data. Consequently, in this work, the authors present an exhaustive survey on the security of FL-based IoMT applications in smart healthcare frameworks. First, the authors introduced IoMT devices, their types, applications, datasets, and the IoMT security framework in detail. Subsequently, the concept of FL, its application domains, and various tools used to develop FL applications are discussed. The significant contribution of FL in deploying secure IoMT systems is presented by focusing on FL-based IoMT applications, patents, real-world FL-based healthcare projects, and datasets. A comparison of FL-based security techniques with other schemes in the smart healthcare ecosystem is also presented. Finally, the authors discussed the challenges faced and potential future research recommendations to deploy secure FL-based IoMT applications in smart healthcare frameworks. © 2023 The Author(s)
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27. |
- Saberi-Movahed, Farid, et al.
(author)
-
Dual Regularized Unsupervised Feature Selection Based on Matrix Factorization and Minimum Redundancy with application in gene selection
- 2022
-
In: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 256
-
Journal article (peer-reviewed)abstract
- Gene expression data have become increasingly important in machine learning and computational biology over the past few years. In the field of gene expression analysis, several matrix factorization-based dimensionality reduction methods have been developed. However, such methods can still be improved in terms of efficiency and reliability. In this paper, an innovative approach to feature selection, called Dual Regularized Unsupervised Feature Selection Based on Matrix Factorization and Minimum Redundancy (DR-FS-MFMR), is introduced. The major focus of DR-FS-MFMR is to discard redundant features from the set of original features. In order to reach this target, the primary feature selection problem is defined in terms of two aspects: (1) the matrix factorization of data matrix in terms of the feature weight matrix and the representation matrix, and (2) the correlation information related to the selected features set. Then, the objective function is enriched by employing two data representation characteristics along with an inner product regularization criterion to perform both the redundancy minimization process and the sparsity task more precisely. To demonstrate the proficiency of the DR-FS-MFMR method, a large number of experimental studies are conducted on nine gene expression datasets. The obtained computational results indicate the efficiency and productivity of DR-FS-MFMR for the gene selection task. © 2022 The Author(s)
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28. |
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29. |
- Yu, Zaiyang, et al.
(author)
-
MV-ReID : 3D Multi-view Transformation Network for Occluded Person Re-Identification
- 2024
-
In: Knowledge-Based Systems. - Amsterdam : Elsevier. - 0950-7051 .- 1872-7409. ; 283
-
Journal article (peer-reviewed)abstract
- Re-identification (ReID) of occluded persons is a challenging task due to the loss of information in scenes with occlusions. Most existing methods for occluded ReID use 2D-based network structures to directly extract representations from 2D RGB (red, green, and blue) images, which can result in reduced performance in occluded scenes. However, since a person is a 3D non-grid object, learning semantic representations in a 2D space can limit the ability to accurately profile an occluded person. Therefore, it is crucial to explore alternative approaches that can effectively handle occlusions and leverage the full 3D nature of a person. To tackle these challenges, in this study, we employ a 3D view-based approach that fully utilizes the geometric information of 3D objects while leveraging advancements in 2D-based networks for feature extraction. Our study is the first to introduce a 3D view-based method in the areas of holistic and occluded ReID. To implement this approach, we propose a random rendering strategy that converts 2D RGB images into 3D multi-view images. We then use a 3D Multi-View Transformation Network for ReID (MV-ReID) to group and aggregate these images into a unified feature space. Compared to 2D RGB images, multi-view images can reconstruct occluded portions of a person in 3D space, enabling a more comprehensive understanding of occluded individuals. The experiments on benchmark datasets demonstrate that the proposed method achieves state-of-the-art results on occluded ReID tasks and exhibits competitive performance on holistic ReID tasks. These results also suggest that our approach has the potential to solve occlusion problems and contribute to the field of ReID. The source code and dataset are available at https://github.com/yuzaiyang123/MV-Reid. © 2023 Elsevier B.V.
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30. |
- Abdusselamoglu, MD, et al.
(author)
-
Dynamics of activating and repressive histone modifications in Drosophila neural stem cell lineages and brain tumors
- 2019
-
In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 146:23
-
Journal article (peer-reviewed)abstract
- During central nervous system (CNS) development, spatiotemporal gene expression programs mediate specific lineage decisions to generate neuronal and glial cell types from neural stem cells (NSCs). However, little is known about the epigenetic landscape underlying these highly complex developmental events. Here, we perform ChIP-seq on distinct subtypes of Drosophila FACS- purified neural stem cells (NSCs) and their differentiated progeny to dissect the epigenetic changes accompanying the major lineage decisions in vivo. By analyzing active and repressive histone modifications, we show that stem cell identity genes are silenced during differentiation by loss of their activating marks and not via repressive histone modifications. Our analysis also uncovers a new set of genes specifically required for altering lineage patterns in type II neuroblasts, one of the two main Drosophila NSC identities. Finally, we demonstrate that this subtype specification in NBs, unlike NSC differentiation, requires Polycomb-group (PcG)-mediated repression.
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31. |
- Acosta, Helena, et al.
(author)
-
The serpin PN1 is a feedback regulator of FGF signaling in germ layer and primary axis formation.
- 2015
-
In: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 1477-9129. ; 142:6, s. 1146-1158
-
Journal article (peer-reviewed)abstract
- Germ layer formation and primary axis development rely on Fibroblast growth factors (FGFs). In Xenopus, the secreted serine protease HtrA1 induces mesoderm and posterior trunk/tail structures by facilitating the spread of FGF signals. Here, we show that the serpin Protease nexin-1 (PN1) is transcriptionally activated by FGF signals, suppresses mesoderm and promotes head development in mRNA-injected embryos. An antisense morpholino oligonucleotide against PN1 has the opposite effect and inhibits ectodermal fate. However, ectoderm and anterior head structures can be restored in PN1-depleted embryos when HtrA1 and FGF receptor activities are diminished, indicating that FGF signals negatively regulate their formation. We show that PN1 binds to and inhibits HtrA1, prevents degradation of the proteoglycan Syndecan 4 and restricts paracrine FGF/Erk signaling. Our data suggest that PN1 is a negative-feedback regulator of FGF signaling and has important roles in ectoderm and head development.
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32. |
- Adam, GIR, et al.
(author)
-
Allele-specific in situ hybridization (ASISH) analysis: a novel technique which resolves differential allelic usage of H19 within the same cell lineage during human placental development
- 1996
-
In: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 122:3, s. 839-847
-
Journal article (peer-reviewed)abstract
- Precursory studies of H19 transcription during human foetal development have demonstrated maternally derived monoallelic expression. Analyses in extra-embryonic tissues, however, have been more equivocal, with discernible levels of expression of the paternal allele of H19 documented in the first trimester placenta. By refining the in situ hybridization technique we have developed an assay to enable the functional imprinting status of H19 to be determined at the cellular level. This assay involves the use of oligonucleotide DNA probes that are able to discriminate between allelic RNA transcripts containing sequence polymorphisms. Biallelic expression of H19 is confined to a subpopulation of cells of the trophoblast lineage, the extravillous cytotrophoblast, while the mesenchymal stroma cells maintain the imprinted pattern of monoallelic expression of H19 throughout placental development. This data demonstrates that the low level of paternal H19 expression previously detected in normal human placenta is not due to a random loss of functional imprinting, but appears to result from a developmentally regulated cell type-specific activation of the paternal allele. In addition, biallelic expression of H19 does not seem to affect the functional imprinting of the insulin-like growth factor II gene, which is monoallelically expressed at relatively high levels in the extra-villous cytotrophoblasts. These results imply that the allelic usage of these two genes in normal human placental development may not be directly analogous to the situation previously documented in the mouse embryo.
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33. |
- Adameyko, I, et al.
(author)
-
Sox2 and Mitf cross-regulatory interactions consolidate progenitor and melanocyte lineages in the cranial neural crest
- 2012
-
In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 139:2, s. 397-410
-
Journal article (peer-reviewed)abstract
- The cellular origin and molecular mechanisms regulating pigmentation of head and neck are largely unknown. Melanocyte specification is controlled by the transcriptional activity of Mitf, but no general logic has emerged to explain how Mitf and progenitor transcriptional activities consolidate melanocyte and progenitor cell fates. We show that cranial melanocytes arise from at least two different cellular sources: initially from nerve-associated Schwann cell precursors (SCPs) and later from a cellular source that is independent of nerves. Unlike the midbrain-hindbrain cluster from which melanoblasts arise independently of nerves, a large center of melanocytes in and around cranial nerves IX-X is derived from SCPs, as shown by genetic cell-lineage tracing and analysis of ErbB3-null mutant mice. Conditional gain- and loss-of-function experiments show genetically that cell fates in the neural crest involve both the SRY transcription factor Sox2 and Mitf, which consolidate an SCP progenitor or melanocyte fate by cross-regulatory interactions. A gradual downregulation of Sox2 in progenitors during development permits the differentiation of both neural crest- and SCP-derived progenitors into melanocytes, and an initial small pool of nerve-associated melanoblasts expands in number and disperses under the control of endothelin receptor B (Ednrb) and Wnt5a signaling.
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34. |
- Agerman, K, et al.
(author)
-
BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development
- 2003
-
In: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 130:8, s. 1479-1491
-
Journal article (peer-reviewed)abstract
- Neurotrophins have multiple functions during peripheral nervous system development such as controlling neuronal survival, target innervation and synaptogenesis. Neurotrophin specificity has been attributed to the selective expression of the Trk tyrosine kinase receptors in different neuronal subpopulations. However, despite overlapping expression of TrkB and TrkC in many sensory ganglia, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) null mutant mice display selective losses in neuronal subpopulations. In the present study we have replaced the coding part of theBDNF gene in mice with that of NT3 (BDNFNT3/NT3)to analyse the specificity and selective roles of BDNF and NT3 during development. Analysis of BDNFNT3/NT3 mice showed striking differences in the ability of NT3 to promote survival, short-range innervation and synaptogenesis in different sensory systems. In the cochlea, specificity is achieved by a tightly controlled spatial and temporal ligand expression. In the vestibular system TrkB or TrkC activation is sufficient to promote vestibular ganglion neuron survival, while TrkB activation is required to promote proper innervation and synaptogenesis. In the gustatory system, NT3 is unable to replace the actions of BDNF possibly because of a temporally selective expression of TrkB in taste neurons. We conclude that there is no general mechanism by which neurotrophin specificity is attained and that specificity is achieved by (i) a tightly controlled spatial and temporal expression of ligands, (ii) different Trk receptors playing distinct roles within the same neuronal subpopulation, or (iii) selective receptor expression in sensory neuron subpopulations.
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35. |
- Aguado, F, et al.
(author)
-
BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2
- 2003
-
In: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 130:7, s. 1267-1280
-
Journal article (peer-reviewed)abstract
- Spontaneous neural activity is a basic property of the developing brain,which regulates key developmental processes, including migration, neural differentiation and formation and refinement of connections. The mechanisms regulating spontaneous activity are not known. By using transgenic embryos that overexpress BDNF under the control of the nestin promoter, we show here that BDNF controls the emergence and robustness of spontaneous activity in embryonic hippocampal slices. Further, BDNF dramatically increases spontaneous co-active network activity, which is believed to synchronize gene expression and synaptogenesis in vast numbers of neurons. In fact, BDNF raises the spontaneous activity of E18 hippocampal neurons to levels that are typical of postnatal slices.We also show that BDNF overexpression increases the number of synapses at much earlier stages (E18) than those reported previously. Most of these synapses were GABAergic, and GABAergic interneurons showed hypertrophy and a 3-fold increase in GAD expression. Interestingly, whereas BDNF does not alter the expression of GABA and glutamate ionotropic receptors, it does raise the expression of the recently cloned K+/Cl- KCC2 co-transporter, which is responsible for the conversion of GABA responses from depolarizing to inhibitory, through the control of the Cl-potential. Together, results indicate that both the presynaptic and postsynaptic machineries of GABAergic circuits may be essential targets of BDNF actions to control spontaneous activity. The data indicate that BDNF is a potent regulator of spontaneous activity and co-active networks, which is a new level of regulation of neurotrophins. Given that BDNF itself is regulated by neuronal activity, we suggest that BDNF acts as a homeostatic factor controlling the emergence, complexity and networking properties of spontaneous networks.
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36. |
- Ahmed, M, et al.
(author)
-
Laminin α2 controls mouse and human stem cell behaviour during midbrain dopaminergic neuron development
- 2019
-
In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 146:16
-
Journal article (peer-reviewed)abstract
- The development of the central nervous system requires the coordination of proliferation and differentiation of neural stem cells. Here, we show that laminin alpha 2 (lm-α2) is a component of the midbrain dopaminergic (mDA) progenitor niche in the ventral midbrain (VM) and identify a concentration-dependent role for lm211 in regulating mDA progenitor proliferation and survival via distinct set of receptors. At high-concentrations, lm211 rich environments maintain mDA progenitors in a proliferative state via integrins α6β1 and α7β1. Whereas low concentrations of lm211 support mDA lineage survival via dystroglycan receptors. We confirmed our findings in vivo where, in the absence of lm-α2, the VM was smaller, with increased apoptosis, and the progenitor pool depleted through premature differentiation resulting in fewer mDA neurons. In examining mDA neuron subtype composition we found a reduction in later-born mDA neurons of the ventral tegmental area, which control a range of cognitive behaviours. Our results identify a novel role for lm in neural development and provide a possible mechanism for autism-like behaviours and brainstem hypoplasia seen in some patients with mutations of the human lm-α2 gene.
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37. |
- Ai, Xingbin, et al.
(author)
-
SULF1 and SULF2 regulate heparan sulfate-mediated GDNF signaling for esophageal innervation
- 2007
-
In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 134:18, s. 3327-3338
-
Journal article (peer-reviewed)abstract
- Heparan sulfate (HS) plays an essential role in extracellular signaling during development. Biochemical studies have established that HS binding to ligands and receptors is regulated by the fine 6-O-sulfated structure of HS; however, mechanisms that control sulfated HS structure and associated signaling functions in vivo are not known. Extracellular HS 6-O-endosulfatases, SULF1 and SULF2, are candidate enzymatic regulators of HS 6-O-sulfated structure and modulate HS-dependent signaling. To investigate Sulf regulation of developmental signaling, we have disrupted Sulf genes in mouse and identified redundant functions of Sulfs in GDNF-dependent neural innervation and enteric glial formation in the esophagus, resulting in esophageal contractile malfunction in Sulf1(-/ -); Sulf2(-/ -) mice. SULF1 is expressed in GDNF-expressing esophageal muscle and SULF2 in innervating neurons, establishing their direct functions in esophageal innervation. Biochemical and cell signaling studies show that Sulfs are the major regulators of HS 6-O-desulfation, acting to reduce GDNF binding to HS and to enhance GDNF signaling and neurite sprouting in the embryonic esophagus. The functional specificity of Sulfs in GDNF signaling during esophageal innervation was established by showing that the neurite sprouting is selectively dependent on GDNF, but not on neurotrophins or other signaling ligands. These findings provide the first in vivo evidence that Sulfs are essential developmental regulators of cellular HS 6-O-sulfation for matrix transmission and reception of GDNF signal from muscle to innervating neurons.
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38. |
- Alenius, Mattias, et al.
(author)
-
Differential function of RNCAM isoforms in precise target selection of olfactory sensory neurons
- 2003
-
In: Development. - : Company of Biologists Ltd. - 0950-1991 .- 1477-9129. ; 130:5, s. 917-927
-
Journal article (peer-reviewed)abstract
- Olfactory sensory neurons (OSNs) are individually specified to express one odorant receptor (OR) gene among similar to1000 different and project with precision to topographically defined convergence sites, the glomeruli, in the olfactory bulb. Although ORs partially determine the location of convergence sites, the mechanism ensuring that axons with different OR identities do not co-converge is unknown. RNCAM (OCAM, NCAM2) is assumed to regulate a broad zonal segregation of projections by virtue of being a homophilic cell adhesion molecule that is selectively expressed on axons terminating in a defined olfactory bulb region. We have identified NADPH diaphorase activity as being an independent marker for RNCAM-negative axons. Analyses of transgenic mice that ectopically express RNCAM in NADPH diaphorasepositive OSNs show that the postulated function of RNCAM in mediating zone-specific segregation of axons is unlikely. Instead, analyses of one OR-specific OSN subpopulation (P2) reveal that elevated RNCAM levels result in an increased number of P2 axons that incorrectly co-converge with axons of other OR identities. Both Gpianchored and transmembrane-bound RNCAM isoforms are localized on axons in the nerve layer, while the transmembrane-bound RNCAM is the predominant isoform on axon terminals within glomeruli. Overexpressing transmembrane-bound RNCAM results in co-convergence events close to the correct target glomeruli. By contrast, overexpression of Gpi-anchored RNCAM results in axons that can bypass the correct target before co-converging on glomeruli located at a distance. The phenotype specific for Gpi-anchored RNCAM is suppressed in mice overexpressing both isoforms, which suggests that two distinct RNCAM isoform-dependent activities influence segregation of OR-defined axon subclasses.
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39. |
- Almeida, Alexandra D, et al.
(author)
-
Spectrum of Fates : a new approach to the study of the developing zebrafish retina.
- 2014
-
In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 141:9, s. 1971-80
-
Journal article (peer-reviewed)abstract
- The ability to image cells live and in situ as they proliferate and differentiate has proved to be an invaluable asset to biologists investigating developmental processes. Here, we describe a Spectrum of Fates approach that allows the identification of all the major neuronal subtypes in the zebrafish retina simultaneously. Spectrum of Fates is based on the combinatorial expression of differently coloured fluorescent proteins driven by the promoters of transcription factors that are expressed in overlapping subsets of retinal neurons. Here, we show how a Spectrum of Fates approach can be used to assess various aspects of neural development, such as developmental waves of differentiation, neuropil development, lineage tracing and hierarchies of fates in the developing zebrafish retina.
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40. |
- Andersson, Elin, et al.
(author)
-
Development of the mesencephalic dopaminergic neuron system is compromised in the absence of neurogenin 2.
- 2006
-
In: Development: For advances in developmental biology and stem cells. - : The Company of Biologists. - 1477-9129. ; 133:3, s. 507-516
-
Journal article (peer-reviewed)abstract
- Neurogenin 2 (Ngn2) is a proneural gene involved in neuronal differentiation and subtype specification in various regions of the nervous system. In the ventral midbrain, Ngn2 is expressed in a spatiotemporal pattern that correlates with the generation of mesencephalic dopaminergic (mesDA) neurons. We show here that lack of Ngn2 impairs the development of mesDA neurons, such that less than half of the normal mesDA neuron number remain in Ngn2 mutant mice at postnatal stages. Analysis of Ngn2 mutant mice during mesDA neurogenesis show that medially located precursors are formed but are arrested in their differentiation at a stage when they have not yet acquired the characteristics of mesDA neuron precursors. Loss of Ngn2 function appears to specifically affect the generation of DA neurons, as the development of other types of neurons within the ventral midbrain is unaltered. Ngn2 is the first example of a gene expressed in progenitors in the ventricular zone of the mesDA neuron domain that is essential for proper mesDA neuron differentiation, and whose loss of function causes impaired mesDA neurogenesis without other major abnormalities in the ventral midbrain.
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41. |
- Andersson, ER, et al.
(author)
-
Notch signaling: simplicity in design, versatility in function
- 2011
-
In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 138:17, s. 3593-3612
-
Journal article (peer-reviewed)abstract
- Notch signaling is evolutionarily conserved and operates in many cell types and at various stages during development. Notch signaling must therefore be able to generate appropriate signaling outputs in a variety of cellular contexts. This need for versatility in Notch signaling is in apparent contrast to the simple molecular design of the core pathway. Here, we review recent studies in nematodes, Drosophila and vertebrate systems that begin to shed light on how versatility in Notch signaling output is generated, how signal strength is modulated, and how cross-talk between the Notch pathway and other intracellular signaling systems, such as the Wnt, hypoxia and BMP pathways, contributes to signaling diversity.
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42. |
- Ando, Koji, et al.
(author)
-
Peri-arterial specification of vascular mural cells from naive mesenchyme requires Notch signaling
- 2019
-
In: Development. - : COMPANY BIOLOGISTS LTD. - 0950-1991 .- 1477-9129. ; 146:2
-
Journal article (peer-reviewed)abstract
- Mural cells (MCs) are essential for blood vessel stability and function; however, the mechanisms that regulate MC development remain incompletely understood, in particular those involved in MC specification. Here, we investigated the first steps of MC formation in zebrafish using transgenic reporters. Using pdgfrb and abcc9 reporters, we show that the onset of expression of abcc9, a pericyte marker in adult mice and zebrafish, occurs almost coincidentally with an increment in pdgfrb expression in peri-arterial mesenchymal cells, suggesting that these transcriptional changes mark the specification of MC lineage cells from naive pdgfrb(low) mesenchymal cells. The emergence of peri-arterial pdgfrb(high) MCs required Notch signaling. We found that pdgfrb-positive cells express notch2 in addition to notch3, and although depletion of notch2 or notch3 failed to block MC emergence, embryos depleted of both notch2 and notch3 lost mesoderm- as well as neural crest-derived pdgfrb(high) MCs. Using reporters that read out Notch signaling and Notch2 receptor cleavage, we show that Notch activation in the mesenchyme precedes specification into pdgfrb(high) MCs. Taken together, these results show that Notch signaling is necessary for peri-arterial MC specification.
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43. |
- Anjard, Christophe, et al.
(author)
-
Requirements for the adenylyl cyclases in the development of Dictyostelium
- 2001
-
In: Development. - 0950-1991 .- 1477-9129. ; 128:18, s. 3649-3654
-
Journal article (peer-reviewed)abstract
- It has been suggested that all intracellular signaling by cAMP during development of Dictyostelium is mediated by the cAMP-dependent protein kinase, PKA, since cells carrying null mutations in the acaA gene that encodes adenylyl cyclase can develop so as to form fruiting bodies under some conditions if PKA is made constitutive by overexpressing the catalytic subunit. However, a second adenylyl cyclase encoded by acrA has recently been found that functions in a cell autonomous fashion during late development. We have found that expression of a modified acaA gene rescues acrA- mutant cells indicating that the only role played by ACR is to produce cAMP. To determine whether cells lacking both adenylyl cyclase genes can develop when PKA is constitutive we disrupted acrA in a acaA- PKA-C(over) strain. When developed at high cell densities, acrA- acaA- PKA-C(over) cells form mounds, express cell type-specific genes at reduced levels and secrete cellulose coats but do not form fruiting bodies or significant numbers of viable spores. Thus, it appears that synthesis of cAMP is required for spore differentiation in Dictyostelium even if PKA activity is high.
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44. |
- Arenas, E, et al.
(author)
-
How to make a midbrain dopaminergic neuron
- 2015
-
In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 142:11, s. 1918-1936
-
Journal article (peer-reviewed)abstract
- Midbrain dopaminergic (mDA) neuron development has been an intense area of research during recent years. This is due in part to a growing interest in regenerative medicine and the hope that treatment for diseases affecting mDA neurons, such as Parkinson's disease (PD), might be facilitated by a better understanding of how these neurons are specified, differentiated and maintained in vivo. This knowledge might help to instruct efforts to generate mDA neurons in vitro, which holds promise not only for cell replacement therapy, but also for disease modeling and drug discovery. In this Primer, we will focus on recent developments in understanding the molecular mechanisms that regulate the development of mDA neurons in vivo, and how they have been used to generate human mDA neurons in vitro from pluripotent stem cells or from somatic cells via direct reprogramming. Current challenges and future avenues in the development of a regenerative medicine for PD will be identified and discussed.
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45. |
- Arnold, TD, et al.
(author)
-
Excessive vascular sprouting underlies cerebral hemorrhage in mice lacking αVβ8-TGFβ signaling in the brain
- 2014
-
In: Development (Cambridge, England). - : The Company of Biologists. - 1477-9129 .- 0950-1991. ; 141:23, s. 4489-4499
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Journal article (peer-reviewed)abstract
- Vascular development of the central nervous system and blood-brain barrier (BBB) induction are closely linked processes. The role of factors that promote endothelial sprouting and vascular leak, such as vascular endothelial growth factor A, are well described, but the factors that suppress angiogenic sprouting and their impact on the BBB are poorly understood. Here, we show that integrin αVβ8 activates angiosuppressive TGFβ gradients in the brain, which inhibit endothelial cell sprouting. Loss of αVβ8 in the brain or downstream TGFβ1-TGFBR2-ALK5-Smad3 signaling in endothelial cells increases vascular sprouting, branching and proliferation, leading to vascular dysplasia and hemorrhage. Importantly, BBB function in Itgb8 mutants is intact during early stages of vascular dysgenesis before hemorrhage. By contrast, Pdgfbret/ret mice, which exhibit severe BBB disruption and vascular leak due to pericyte deficiency, have comparatively normal vascular morphogenesis and do not exhibit brain hemorrhage. Our data therefore suggest that abnormal vascular sprouting and patterning, not BBB dysfunction, underlie developmental cerebral hemorrhage.
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46. |
- Aspock, G, et al.
(author)
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The Caenorhabditis elegans ems class homeobox gene ceh-2 is required for M3 pharynx motoneuron function
- 2003
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In: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 130:15, s. 3369-3378
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Journal article (peer-reviewed)abstract
- Several homeobox genes, for example those of the ems class, play important roles in animal head development. We report on the expression pattern and function of ceh-2, the Caenorhabditis elegans ems/Emx ortholog. CEH-2 protein is restricted to the nuclei of one type of small muscle cell, one type of epithelial cell, and three types of neurons in the anterior pharynx in the head. We have generated a deletion allele of ceh-2 that removes the homeobox. Animals homozygous for this deletion are viable and fertile, but grow slightly slower and lay fewer eggs than wild type. We assayed the function of two types of pharynx neurons that express ceh-2, the pairs M3 and NSM. M3 activity is substantially reduced in electropharyngeograms of ceh-2 deletion mutants; this defect can account for the observed retardation in larval development, as M3 activity is known to be necessary for effective feeding. NSM function and metabolism are normal based on the assays used. All cells that express ceh-2 in wild type are present in the ceh-2mutant and have normal morphologies. Therefore, unlike other ems/Emxgenes, ceh-2 seems to be important for a late differentiation step and not for neuron specification or regional patterning. Because the CEH-2 homeodomain is well conserved, we tested whether ceh-2 can rescue ems- brain defects in Drosophila, despite the apparent differences in biological roles. We found that the C. elegans ems ortholog is able to substitute for fly ems in brain development, indicating that sequence conservation rather than conservation of biological function is important.
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47. |
- Astorga, Jeanette, 1976, et al.
(author)
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Hedgehog induction of murine vasculogenesis is mediated by Foxf1 and Bmp4
- 2007
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In: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 134:20, s. 3753-61
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Journal article (peer-reviewed)abstract
- The first vasculature of the developing vertebrate embryo forms by assembly of endothelial cells into simple tubes from clusters of mesodermal angioblasts. Maturation of this vasculature involves remodeling, pruning and investment with mural cells. Hedgehog proteins are part of the instructive endodermal signal that triggers the assembly of the first primitive vessels in the mesoderm. We used a combination of genetic and in vitro culture methods to investigate the role of hedgehogs and their targets in murine extraembryonic vasculogenesis. We show that Bmps, in particular Bmp4, are crucial for vascular tube formation, that Bmp4 expression in extraembryonic tissues requires the forkhead transcription factor Foxf1 and that the role of hedgehog proteins in this process is to activate Foxf1 expression in the mesoderm. We show in the allantois that genetic disruption of hedgehog signaling (Smo(-/-)) has no effect on Foxf1 expression, and neither Bmp4 expression nor vasculogenesis are disturbed. By contrast, targeted inactivation of Foxf1 leads to loss of allantoic Bmp4 and vasculature. In vitro, the avascular Foxf1(-/-) phenotype can be rescued by exogenous Bmp4, and vasculogenesis in wild-type tissue can be blocked by the Bmp antagonist noggin. Hedgehogs are required for activation of Foxf1, Bmp4 expression and vasculogenesis in the yolk sac. However, vasculogenesis in Smo(-/-) yolk sacs can be rescued by exogenous Bmp4, consistent with the notion that the role of hedgehog signaling in primary vascular tube formation is as an activator of Bmp4, via Foxf1.
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48. |
- Baudet, C, et al.
(author)
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Positive and negative interactions of GDNF, NTN and ART in developing sensory neuron subpopulations, and their collaboration with neurotrophins
- 2000
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In: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 127:20, s. 4335-4344
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Journal article (peer-reviewed)abstract
- Glial cell line-derived neurotrophic factor (GDNF), neurturin (NTN) and neublastin/artemin (ART) are distant members of the transforming growth factor β; family, and have been shown to elicit neurotrophic effects upon several classes of peripheral and central neurons. Limited information from in vitro and expression studies has also substantiated a role for GDNF family ligands in mammalian somatosensory neuron development. Here, we show that although dorsal root ganglion (DRG) sensory neurons express GDNF family receptors embryonically, they do not survive in response to their ligands. The regulation of survival emerges postnatally for all GDNF family ligands. GDNF and NTN support distinct subpopulations that can be separated with respect to their expression of GDNF family receptors, whereas ART supports neurons in populations that are also responsive to GDNF or NTN. Sensory neurons that coexpress GDNF family receptors are medium sized, whereas small-caliber nociceptive cells preferentially express a single receptor. In contrast to brain-derived neurotrophic factor (BDNF)-dependent neurons, embryonic nerve growth factor (NGF)-dependent nociceptive neurons switch dependency to GDNF, NTN and ART postnatally. Neurons that survive in the presence of neurotrophin 3 (NT3) or neurotrophin 4 (NT4), including proprioceptive afferents, Merkel end organs and D-hair afferents, are also supported by GDNF family ligands neonatally, although at postnatal stages they lose their dependency on GDNF and NTN. At late postnatal stages, ART prevents survival elicited by GDNF and NTN. These data provide new insights on the roles of GDNF family ligands in sensory neuron development.
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49. |
- Beatus, P, et al.
(author)
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The notch 3 intracellular domain represses notch 1-mediated activation through Hairy/Enhancer of split (HES) promoters
- 1999
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In: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 126:17, s. 3925-3935
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Journal article (peer-reviewed)abstract
- The Notch signaling pathway is important for cellular differentiation. The current view is that the Notch receptor is cleaved intracellularly upon ligand activation. The intracellular Notch domain then translocates to the nucleus, binds to Suppressor of Hairless (RBP-Jk in mammals), and acts as a transactivator of Enhancer of Split (HES in mammals) gene expression. In this report we show that the Notch 3 intracellular domain (IC), in contrast to all other analysed Notch ICs, is a poor activator, and in fact acts as a repressor by blocking the ability of the Notch 1 IC to activate expression through the HES-1 and HES-5 promoters. We present a model in which Notch 3 IC interferes with Notch 1 IC-mediated activation at two levels. First, Notch 3 IC competes with Notch 1 IC for access to RBP-Jk and does not activate transcription when positioned close to a promoter. Second, Notch 3 IC appears to compete with Notch 1 IC for a common coactivator present in limiting amounts. In conclusion, this is the first example of a Notch IC that functions as a repressor in Enhancer of Split/HES upregulation, and shows that mammalian Notch receptors have acquired distinct functions during evolution.
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50. |
- Benito-Sipos, Jonathan, et al.
(author)
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A genetic cascade involving klumpfuss, nab and castor specifies the abdominal leucokinergic neurons in the Drosophila CNS
- 2010
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In: DEVELOPMENT. - : Company of Biologists Ltd. - 0950-1991 .- 1477-9129. ; 137:19, s. 3327-3336
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Journal article (peer-reviewed)abstract
- Identification of the genetic mechanisms underlying the specification of large numbers of different neuronal cell fates from limited numbers of progenitor cells is at the forefront of developmental neurobiology. In Drosophila, the identities of the different neuronal progenitor cells, the neuroblasts, are specified by a combination of spatial cues. These cues are integrated with temporal competence transitions within each neuroblast to give rise to a specific repertoire of cell types within each lineage. However, the nature of this integration is poorly understood. To begin addressing this issue, we analyze the specification of a small set of peptidergic cells: the abdominal leucokinergic neurons. We identify the progenitors of these neurons, the temporal window in which they are specified and the influence of the Notch signaling pathway on their specification. We also show that the products of the genes klumpfuss, nab and castor play important roles in their specification via a genetic cascade.
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