Signaling pathways as linear transmitters

One challenge in biology is to make sense of the complexity of biological networks. A good system to approach this is signaling pathways, whose well-characterized molecular details allow us to relate the internal processes of each pathway to their input-output behavior. In this study, we analyzed mathematical models of three metazoan signaling pathways: the canonical Wnt, MAPK/ERK, and Tgfβ pathways. We find an unexpected convergence: the three pathways behave in some physiological contexts as linear signal transmitters. Testing the results experimentally, we present direct measurements of linear input-output behavior in the Wnt and ERK pathways. Analytics from each model further reveal that linearity arises through different means in each pathway, which we tested experimentally in the Wnt and ERK pathways. Linearity is a desired property in engineering where it facilitates fidelity and superposition in signal transmission. Our findings illustrate how cells tune different complex networks to converge on the same behavior

Symmetrization in jellyfish: reorganization to regain function, and not lost parts

We recently reported a previously unidentified strategy of self-repair in the moon jellyfish Aurelia aurita. Rather than regenerating lost parts, juvenile Aurelia reorganize remaining parts to regain essential body symmetry. This process that we called symmetrization is rapid and frequent, and is not driven by cell proliferation or cell death. Instead, the swimming machinery generates mechanical forces that drive symmetrization. We found evidence for symmetrization across three other species of jellyfish (Chrysaora pacifica, Mastigias sp., and Cotylorhiza tuberculata). We propose reorganization to regain function without recovery of initial morphology as a potentially broad class of self-repair strategy beyond radially symmetrical animals, and discuss the implications of this finding on the evolution of self-repair strategies in animals

Allosteric proteins as logarithmic sensors

Many sensory systems, from vision and hearing in animals to signal transduction in cells, respond to fold changes in signal relative to background. Responding to fold change requires that the system senses signal on a logarithmic scale, responding identically to a change in signal level from 1 to 3, or from 10 to 30. It is an ongoing search in the field to understand the ways in which a logarithmic sensor can be implemented at the molecular level. In this work, we present evidence that logarithmic sensing can be implemented with a single protein, by means of allosteric regulation. Specifically, we find that mathematical models show that allosteric proteins can respond to stimuli on a logarithmic scale. Next, we present evidence from measurements in the literature that some allosteric proteins do operate in a parameter regime that permits logarithmic sensing. Finally, we present examples suggesting that allosteric proteins are indeed used in this capacity: allosteric proteins play a prominent role in systems where fold-change detection has been proposed. This finding suggests a role as logarithmic sensors for the many allosteric proteins across diverse biological processes

Evidence that fold-change, and not absolute level, of β-catenin dictates Wnt signaling

In response to Wnt stimulation, β-catenin accumulates and activates target genes. Using modeling and experimental analysis, we found that the level of β-catenin is sensitive to perturbations in the pathway, such that cellular variation would be expected to alter the signaling outcome. One unusual parameter was robust: the fold-change in β-catenin level (post-Wnt/pre-Wnt). In Xenopus, dorsal-anterior development and target gene expression are robust to perturbations that alter the final level but leave the fold-change intact. These suggest, first, that despite cellular noise, the cell responds reliably to Wnt stimulation by maintaining a robust fold-change in β-catenin. Second, the transcriptional machinery downstream of the Wnt pathway does not simply read the β-catenin level after Wnt stimulation but computes fold-changes in β-catenin. Analogous to Weber's Law in sensory physiology, some gene transcription networks must respond to fold-changes in signals, rather than absolute levels, which may buffer stochastic, genetic, and environmental variation

Pengaruh Teknik Diskusi Berpasangan dengan Bantuan Media Video Klip terhadap Kemampuan Menulis Naskah Drama Siswa Kelas XI SMA Negeri 90 Jakarta

Tujuan penelitian ini untuk mengetahui pengaruh penggunaan teknik diskusi berpasangan dengan bantuan media video klip terhadap kemampuan menulis naskah drama siswa kelas XI SMA Negeri 90 Jakarta. Populasi penelitian adalah siswa kelas XI SMA Negeri 90 Jakarta. Pengambilan sampel dilakukan random sampling. Sampel yang digunakan, yaitu dari sembilan kelas XI yang ada di SMA 90 Jakarta diambil 2 kelas yang ditentukan secara acak. Satu kelas dijadikan kelompok eksperimen, yaitu kelas XI IPA 2 yang mendapat perlakuan berupa penggunaan teknik diskusi berpasangan dengan bantuan media video klip. Satu kelas lain, yaitu kelas XI IPA 1 dijadikan sebagai kelompok kontrol. Metode yang digunakan pada kelompok kontrol, yaitu metode ceramah dan tanya jawab. Penelitian ini menggunakan instrumen berupa tes menulis naskah drama. Hasil menulis naskah drama siswa diberi skor dengan menggunakan kisi-kisi penilaian mengenai aspek orisinalitas ide, penokohan, teknik penulisan (dialog dan kramagung), alur dan latar. Uji persyaratan analisis data dilakukan terlebih dahulu, yaitu uji normalitas dengan menggunakan uji Liliefors. Dari hasil perhitungan uji normalitas, pada kelas eksperimen diperoleh Lo pretes = 0,1079 dan Lo postes = 0,0709. Sementara itu, di kelas kontrol diperoleh Lo pretes = 0,1001 dan Lo postes = 0,1251. Adapun Lt (Ltabel) sebesar 0,1438 pada taraf signifikansi 0,05. Dengan demikian, sampel penelitian ini berdistribusi normal karena Lo lebih kecil dari Lt. Untuk uji homogenitas, digunakan rumus uji Barlet. Dari hasil penghitungan diperoleh X2 tabel sebesar 3,84 sedangkan X2 hitung sebesar 1,63 dengan derajat kebebasan (dk) = (N-1) = 38– 1 = 37, dan taraf signifikan α = 0,05. Maka diperoleh X2 tabel = 3,84 lebih kecil daripada X2 hitung= 1,63 dengan melihat kriteria pengujian yang telah dijelaskan sebelumnya maka dapat disimpulkan bahwa data tersebut mempunyai varians yang sama atau homogen. Selanjutnya, dilakukan pengujian hipotesis dengan uji-t. berdasarkan hasil perhitungan, diperoleh thitung = 2,679 dan ttabel = 1,665 dalam α = 0,05. Dengan demikian, dapat disimpulkan hipotesis penelitian yang mengatakan bahwa terdapat pengaruh teknik diskusi berpasangan dengan bantuan media video klip terhadap kemampuan menulis naskah drama siswa kelas kelas XI SMA Negeri 90 Jakarta diterima. Berdasarkan hasil penelitian, pengunaan teknik diskusi berpasangan dengan bantuan media video klip dapat diterapkan sebagai salah satu media pengajaran untuk pembelajaran menulis naskah drama. Media ini pada dasarnya memiliki kelebihan dapat membuat siswa lebih termotivasi dalam menulis naskah drama, kreatif dalam mengungkapkan perasaan, dan variatif dalam pembentukkan dialog. Selain itu membantu siswa menuangkan gagasan–gagasan ke dalam sebuah naskah drama dan memberikan pengalaman belajar yang menyenangkan karena pembelajaran tidak berjalan secara individu. Kata kunci: teknik diskusi berpasangan dengan bantuan media video klip, menulis naskah drama

Kemampuan Menulis Puisi Pengaruh Media Pembelajaran dan Penguasaan Diksi

Penelitian ini bertujuan untuk mengetahui media pembelajaran dan penguasaan diksi terhadap kemampuan menulis puisi. Penelitian ini menggunakan metode eksperimen, dengan populasi siswa SMK Negeri di Jakarta Timur sejumlah 796 siswa, dan teknik sampling acak diperoleh sampel sebesar 80 siswa. Teknis analisis statistik yang dipergunakan adalah ANOVA dua jalur pada taraf signifikan ? = 0,05. Hasil penelitian membuktikan bahwa media pembelajaran dan penguasaan diksi berkontribusi terhadap kemampuan menulis puisi.Kata Kunci: Media Pembelajaran, Penguasaan Diksi, Kemampuan Menulis Puis

Sensing relative signal in the Tgf-β/Smad pathway

How signaling pathways function reliably despite cellular variation remains a question in many systems. In the transforming growth factor-β (Tgf-β) pathway, exposure to ligand stimulates nuclear localization of Smad proteins, which then regulate target gene expression. Examining Smad3 dynamics in live reporter cells, we found evidence for fold-change detection. Although the level of nuclear Smad3 varied across cells, the fold change in the level of nuclear Smad3 was a more precise outcome of ligand stimulation. The precision of the fold-change response was observed throughout the signaling duration and across Tgf-β doses, and significantly increased the information transduction capacity of the pathway. Using single-molecule FISH, we further observed that expression of Smad3 target genes (ctgf, snai1, and wnt9a) correlated more strongly with the fold change, rather than the level, of nuclear Smad3. These findings suggest that some target genes sense Smad3 level relative to background, as a strategy for coping with cellular noise

The incoherent feedforward loop can provide fold-change detection in gene regulation

Many sensory systems (e.g., vision and hearing) show a response that is proportional to the fold-change in the stimulus relative to the background, a feature related to Weber's Law. Recent experiments suggest such a fold-change detection feature in signaling systems in cells: a response that depends on the fold-change in the input signal, and not on its absolute level. It is therefore of interest to find molecular mechanisms of gene regulation that can provide such fold-change detection. Here, we demonstrate theoretically that fold-change detection can be generated by one of the most common network motifs in transcription networks, the incoherent feedforward loop (I1-FFL), in which an activator regulates both a gene and a repressor of the gene. The fold-change detection feature of the I1-FFL applies to the entire shape of the response, including its amplitude and duration, and is valid for a wide range of biochemical parameters

Signaling pathways as linear transmitters

One challenge in biology is to make sense of the complexity of biological networks. A good system to approach this is signaling pathways, whose well-characterized molecular details allow us to relate the internal processes of each pathway to their input-output behavior. In this study, we analyzed mathematical models of three metazoan signaling pathways: the canonical Wnt, MAPK/ERK, and Tgfβ pathways. We find an unexpected convergence: the three pathways behave in some physiological contexts as linear signal transmitters. Testing the results experimentally, we present direct measurements of linear input-output behavior in the Wnt and ERK pathways. Analytics from each model further reveal that linearity arises through different means in each pathway, which we tested experimentally in the Wnt and ERK pathways. Linearity is a desired property in engineering where it facilitates fidelity and superposition in signal transmission. Our findings illustrate how cells tune different complex networks to converge on the same behavior