| 1. |
- El-Sayed, Najib M., et al.
(författare)
-
The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease.
- 2005
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5733, s. 409-15
-
Tidskriftsartikel (refereegranskat)abstract
- Whole-genome sequencing of the protozoan pathogen Trypanosoma cruzi revealed that the diploid genome contains a predicted 22,570 proteins encoded by genes, of which 12,570 represent allelic pairs. Over 50% of the genome consists of repeated sequences, such as retrotransposons and genes for large families of surface molecules, which include trans-sialidases, mucins, gp63s, and a large novel family (>1300 copies) of mucin-associated surface protein (MASP) genes. Analyses of the T. cruzi, T. brucei, and Leishmania major (Tritryp) genomes imply differences from other eukaryotes in DNA repair and initiation of replication and reflect their unusual mitochondrial DNA. Although the Tritryp lack several classes of signaling molecules, their kinomes contain a large and diverse set of protein kinases and phosphatases; their size and diversity imply previously unknown interactions and regulatory processes, which may be targets for intervention.
|
|
| 2. |
|
|
| 3. |
- Heusermann, W, et al.
(författare)
-
Exosomes surf on filopodia to enter cells at endocytic hot spots, traffic within endosomes, and are targeted to the ER
- 2016
-
Ingår i: The Journal of cell biology. - : Rockefeller University Press. - 1540-8140 .- 0021-9525. ; 213:2, s. 173-184
-
Tidskriftsartikel (refereegranskat)abstract
- Exosomes are nanovesicles released by virtually all cells, which act as intercellular messengers by transfer of protein, lipid, and RNA cargo. Their quantitative efficiency, routes of cell uptake, and subcellular fate within recipient cells remain elusive. We quantitatively characterize exosome cell uptake, which saturates with dose and time and reaches near 100% transduction efficiency at picomolar concentrations. Highly reminiscent of pathogenic bacteria and viruses, exosomes are recruited as single vesicles to the cell body by surfing on filopodia as well as filopodia grabbing and pulling motions to reach endocytic hot spots at the filopodial base. After internalization, exosomes shuttle within endocytic vesicles to scan the endoplasmic reticulum before being sorted into the lysosome as their final intracellular destination. Our data quantify and explain the efficiency of exosome internalization by recipient cells, establish a new parallel between exosome and virus host cell interaction, and suggest unanticipated routes of subcellular cargo delivery.
|
|
| 4. |
|
|
| 5. |
- Aydt, H., et al.
(författare)
-
Preventive what-if analysis in symbiotic simulation
- 2008
-
Ingår i: Proc. Winter Simul. Conf.. - 9781424427086 ; , s. 750-758
-
Konferensbidrag (refereegranskat)abstract
- The what-if analysis process is essential in symbiotic simulation systems. It is responsible for creating a number of alternative what-if scenarios and evaluating their performance by means of simulation. Most applications use a reactive approach for triggering the what-if analysis process. In this paper we describe a preventive triggering approach which is based on the detection of a future critical condition in the forecast of a physical system. With decreasing probability of a critical condition, using preventive what-if analysis becomes undesirable. We introduce the notion of a Gvalue and explain how this metric can be used to decide whether or not to use preventive what-if analysis. In addition, we give an example for a possible application in semiconductor manufacturing.
|
|
| 6. |
- Aydt, Heiko, et al.
(författare)
-
Toward an Evolutionary Computing Modeling Language
- 2011
-
Ingår i: IEEE Transactions on Evolutionary Computation. - 1089-778X .- 1941-0026. ; 15:2, s. 230-247
-
Tidskriftsartikel (refereegranskat)abstract
- The importance of domain knowledge in the design of effective evolutionary algorithms (EAs) is widely acknowledged in the meta-heuristics community. In the last few decades, a plethora of EAs has been manually designed by domain experts for solving domain-specific problems. Specialization has been achieved mainly by embedding available domain knowledge into the algorithms. Although programming libraries have been made available to construct EAs, a unifying framework for designing specialized EAs across different problem domains and branches of evolutionary computing does not exist yet. In this paper, we address this issue by introducing an evolutionary computing modeling language (ECML) which is based on the unified modeling language (UML). ECML incorporates basic UML elements and introduces new extensions that are specially needed for the evolutionary computation domain. Subsequently, the concept of meta evolutionary algorithms (MEAs) is introduced as a family of EAs that is capable of interpreting ECML. MEAs are solvers that are not restricted to a particular problem domain or branch of evolutionary computing through the use of ECML. By separating problem-specific domain knowledge from the EA implementation, we show that a unified framework for evolutionary computation can be attained. We demonstrate our approach by applying it to a number of examples.
|
|
| 7. |
- Gupta, Dhanu, et al.
(författare)
-
Amelioration of systemic inflammation via the display of two different decoy protein receptors on extracellular vesicles
- 2021
-
Ingår i: Nature Biomedical Engineering. - Stockholm : Karolinska Institutet, Dept of Laboratory Medicine. - 2157-846X.
-
Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) can be functionalized to display specific protein receptors on their surface. However, surface-display technology typically labels only a small fraction of the EV population. Here, we show that the joint display of two different therapeutically relevant protein receptors on EVs can be optimized by systematically screening EV-loading protein moieties. We used cytokine-binding domains derived from tumour necrosis factor receptor 1 (TNFR1) and interleukin-6 signal transducer (IL-6ST), which can act as decoy receptors for the pro-inflammatory cytokines tumour necrosis factor alpha (TNF-α) and IL-6, respectively. We found that the genetic engineering of EV-producing cells to express oligomerized exosomal sorting domains and the N-terminal fragment of syntenin (a cytosolic adaptor of the single transmembrane domain protein syndecan) increased the display efficiency and inhibitory activity of TNFR1 and IL-6ST and facilitated their joint display on EVs. In mouse models of systemic inflammation, neuroinflammation and intestinal inflammation, EVs displaying the cytokine decoys ameliorated the disease phenotypes with higher efficacy as compared with clinically approved biopharmaceutical agents targeting the TNF-α and IL-6 pathways.
|
|
| 8. |
|
|
| 9. |
- Nene, Vishvanath, et al.
(författare)
-
Genome sequence of Aedes aegypti, a major arbovirus vector.
- 2007
-
Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5832, s. 1718-23
-
Tidskriftsartikel (refereegranskat)abstract
- We present a draft sequence of the genome of Aedes aegypti, the primary vector for yellow fever and dengue fever, which at approximately 1376 million base pairs is about 5 times the size of the genome of the malaria vector Anopheles gambiae. Nearly 50% of the Ae. aegypti genome consists of transposable elements. These contribute to a factor of approximately 4 to 6 increase in average gene length and in sizes of intergenic regions relative to An. gambiae and Drosophila melanogaster. Nonetheless, chromosomal synteny is generally maintained among all three insects, although conservation of orthologous gene order is higher (by a factor of approximately 2) between the mosquito species than between either of them and the fruit fly. An increase in genes encoding odorant binding, cytochrome P450, and cuticle domains relative to An. gambiae suggests that members of these protein families underpin some of the biological differences between the two mosquito species.
|
|
| 10. |
- Saulnier, DD, et al.
(författare)
-
Staying afloat: community perspectives on health system resilience in the management of pregnancy and childbirth care during floods in Cambodia
- 2020
-
Ingår i: BMJ global health. - : BMJ. - 2059-7908. ; 5:4
-
Tidskriftsartikel (refereegranskat)abstract
- Resilient health systems have the capacity to continue providing health services to meet the community’s diverse health needs following floods. This capacity is related to how the community manages its own health needs and the community and health system’s joined capacities for resilience. Yet little is known about how community participation influences health systems resilience. The purpose of this study was to understand how community management of pregnancy and childbirth care during floods is contributing to the system’s capacity to absorb, adapt or transform as viewed through a framework on health systems resilience.MethodsEight focus group discussions and 17 semi-structured interviews were conducted with community members and leaders who experienced pregnancy or childbirth during recent flooding in rural Cambodia. The data were analysed by thematic analysis and discussed in relation to the resilience framework.ResultsThe theme ‘Responsible for the status quo’ reflected the community’s responsibility to find ways to manage pregnancy and childbirth care, when neither the expectations of the health system nor the available benefits changed during floods. The theme was informed by notions on: i) developmental changes, the unpredictable nature of floods and limited support for managing care, ii) how information promoted by the public health system led to a limited decision-making space for pregnancy and childbirth care, iii) a desire for security during floods that outweighed mistrust in the public health system and iv) the limits to the coping strategies that the community prepared in case of flooding.ConclusionsThe community mainly employed absorptive strategies to manage their care during floods, relieving the burden on the health system, yet restricted support and decision-making may risk their capacity. Further involvement in decision-making for care could help improve the health system’s resilience by creating room for the community to adapt and transform when experiencing floods.
|
|
