Reconstructing the TIR side of the Myddosome: a paradigm for TIR-TIR interactions?

Members of the Toll-like receptor and interleukin-1 (IL-1) receptor families all signal via Toll/IL-1R (TIR) domain-driven assemblies with adaptors such as MyD88. We here combine the mammalian two-hybrid system MAPPIT and saturation mutagenesis to complement and extend crystallographic and nuclear magnetic resonance data, and reveal how TIR domains interact. We fully delineate the interaction sites on the MyD88 TIR domain for homo-oligomerization and for interaction with Mal and TLR4. Interactions between three sites drive MyD88 homo-oligomerization. The BB-loop interacts with the alpha E-helix, explaining how BB-loop mimetics inhibit MyD88 signaling. The alpha C'-helix interacts symmetrically. The MyD88 TIR domains thus assemble into a left-handed helix, compatible with the Myddosome death domain crystal structure. This assembly explains activation of MyD88 by Mal and by an oncogenic mutation, and regulation by phosphorylation. These findings provide a paradigm for the interaction of mammalian TIR domains

Cell Size Control in Yeast

Cell size is an important adaptive trait that influences nearly all aspects of cellular physiology. Despite extensive characterization of the cell-cycle regulatory network, the molecular mechanisms coupling cell growth to division, and thereby controlling cell size, have remained elusive. Recent work in yeast has reinvigorated the size control field and suggested provocative mechanisms for the distinct functions of setting and sensing cell size. Further examination of size-sensing models based on spatial gradients and molecular titration, coupled with elucidation of the pathways responsible for nutrient-modulated target size, may reveal the fundamental principles of eukaryotic cell size control

A low energy house

PFC del programa Erasmus EPS elaborat a Copenhagen University College of EngineeringTreball desenvolupat dins el marc del programa 'European Project Semester'.As international students taking part in the European Project Semester – EPS, we were asked to participate in a project called A Low Energy House, in collaboration with a Danish consulting engineering company, Cenergia. The motivation to develop this project has been the present concern of climate change, and depletion of fossil energy resources available. Among some other solutions, a good way to face this problem is to approach the house consumption more efficiently. The main aim of the project is to design the installations for a real block apartment, which will be soon built in the Copenhagen area, to certify it as a Class 1 building, meaning that its annual energy consumption must be less than 35’4 kWh/m2 To reach our goal we worked on two differentiated parts: passive solutions and active solutions. The first one involves insulation, ventilation, glazing and day lighting. While the second one deal with heating systems, solar systems, electric lighting and home automation. . After implementing all our solutions in the building, and try to change the occupants’ behaviour through guidelines, we can say we reach a global consumption of 33’5kWh/m²/year for the whole building

Effect of the (n +1) residue on peptide deamidation

Deamidation occurs spontaneously in peptides and proteins [1]. Many reports show that deamidation has a substantial effect on protein structure, function and stability. An experimental study on pentapeptides [2] shows that Asn deamidation rates are directly related to primary structure near Asn, with a prominent effect from the carboxyl-side (Yyy). We explore the correlation between experimental deamidation rates and primary structure for two pentapeptides (Yyy=Gly, Ile), to identify the factors causing this dependence. A pentapeptide in a water box is subject to Replica-Exchange Molecular Dynamics (REMD) calculations performed with GROMACS 4 software. Furthermore, a succinimide-mediated reaction [3] is investigated with QM/MM calculations utilizing the CP2K code using Nudged-Elastic-Band (NEB) calculations.[p] [p] [p][1] Robinson, NE, Robinson, AB Proc. Natl. Acad. Sci. USA 2001 , 98, 944.[p][2] Robinson, NE J. Peptide Res. 2004 , 63, 426.[p][3] Catak, S., Monard, G., Aviyente, V., Ruiz-López, MF J. Phys. Chem. A 2009 , 113, 1111

Penerapan Pendekatan Kontekstual untuk Meningkatkan Prestasi Belajar Matematika pada Materi Lingkaran Bagi Siswa Kelas VIII C SMP Negeri 1 Karangawen Demak Tahun Pelajaran 2008/2009

Sampai saat ini, pendidikan masih memegang peranan yang sangat penting. Dengan adanya pendidikan, sumber daya manusia dapat berkembang menuju ke arah yang lebih baik dan salah satunyanya adalah dapat dilihat dari prestasi belajar yang telah dicapai oleh peserta didik. Dalam perkembangannya, guru harus memiliki keahlian untuk memilih dan menggunakan metode pengajaran yang sesuai dengan mata pelajaran khususnya matematika serta mengetahui kondisi peserta didik disamping penguasaan keterampilan yang lain karena matematika merupakan mata pelajaran yang dianggap sulit oleh sebagian besar peserta didik. Untuk mengatasi permasalahan tersebut, diperlukan suatu metode pembelajaran yang berguna untuk meningkatkan minat agar aktivitas dan prestasi belajar peserta didik optimal yaitu dengan menggunakan pendekatan kontekstual. Penelitian ini ditempuh melalui 3 siklus, tiap siklus terdiri atas 4 tahapan, yaitu perencanaan, pelaksanaan/tindakan, pengamatan/observasi, dan refleksi. Metode pengambilan data dengan pemanfaatan Lembar Kerja, tes tertulis (evaluasi), lembar pengamatan guru dan lembar pengamatan peserta didik serta angket refleksi peserta didik. Hasil penelitian menunjukkan persentase ketuntasan belajar mengalami peningkatan yaitu dari 86,55 % pada siklus I menjadi 87,14 % pada siklus II dan meningkat lagi menjadi 90,81 % pada siklus III. Aktivitas peserta didik mengalami peningkatan dari persentase 72,5 % pada siklus I menjadi 88,75 % pada siklus II dan meningkat lagi menjadi 90 % pada siklus III. Aktivitas guru yang diperoleh lembar pengamatan aktivitas guru mengalami peningkatan dari persentase 71,6 % pada siklus I menjadi 87,5 % pada siklus II dan meningkat lagi menjadi 92 % pada siklus III. Dari hasil yang diperoleh dapat disimpulkan bahwa dengan penerapan pendekatan kontekstual pada materi lingkaran dapat meningkatkan prestasi belajar dan aktivitas peserta didik kelas VIII?é?á C SMP Negeri 1 Karangawen Demak sesuai dengan indikator yang ditentukan. ?é?

Normal cycles and curvature measures of sets with d.c. boundary

We show that for every compact domain in a Euclidean space with d.c. (delta-convex) boundary there exists a unique Legendrian cycle such that the associated curvature measures fulfil a local version of the Gauss-Bonnet formula. This was known in dimensions two and three and was open in higher dimensions. In fact, we show this property for a larger class of sets including also lower-dimensional sets. We also describe the local index function of the Legendrian cycles and we show that the associated curvature measures fulfill the Crofton formula.Comment: 22 pp, corrected versio