Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression

Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled, or heuristic approximations of the underlying regulatory mechanisms. We have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence, as a function of transcription factor concentrations and their DNA-binding specificities. It uses statistical thermodynamics theory to model not only protein-DNA interaction, but also the effect of DNA-bound activators and repressors on gene expression. In addition, the model incorporates mechanistic features such as synergistic effect of multiple activators, short range repression, and cooperativity in transcription factor-DNA binding, allowing us to systematically evaluate the significance of these features in the context of available expression data. Using this model on segmentation-related enhancers in Drosophila, we find that transcriptional synergy due to simultaneous action of multiple activators helps explain the data beyond what can be explained by cooperative DNA-binding alone. We find clear support for the phenomenon of short-range repression, where repressors do not directly interact with the basal transcriptional machinery. We also find that the binding sites contributing to an enhancer's function may not be conserved during evolution, and a noticeable fraction of these undergo lineage-specific changes. Our implementation of the model, called GEMSTAT, is the first publicly available program for simultaneously modeling the regulatory activities of a given set of sequences

Transposable elements have rewired the core regulatory network of human embryonic stem cells

10.1038/ng.600Nature Genetics427631-634NGEN

ANALISIS PEMANFAATAN SENAYAN LIBRARY MANAGEMENT SYSTEM (SLiMS) DI KANTOR PERPUSTAKAAN DAN ARSIP DAERAH KOTA SALATIGA

Tujuan penelitian ini adalah untuk menganalisis pemanfaatan Senayan Library Management System (SLiMS) di Kantor Perpustakaan dan Arsip Daerah Kota Salatiga berdasarkan aspek kemanfaatan dan kemudahan dalam teori Technology Acceptance Model (TAM). Dalam penelitian ini peneliti menggunakan metode deskriptif kualitatif. Informan dipilih berdasarkan kriteria yang telah peneliti tentukan sebelumnya sejumlah 9 orang yang terdiri dari 6 orang pengelola perpustakaan dan 3 pemustaka. Kriteria informan untuk pengelola perpustakaan adalah mereka yang berhubungan langsung dengan SLiMS dalam kegiatan sehari-hari, sedangkan informan pemustaka adalah pemustaka yang menggunakan OPAC minimal 3 kali dalam satu bulan dan sedang melakukan penelusuran dengan OPAC saat peneliti melakukan observasi. Analisis data yang diperoleh selama penelitian menunjukan hasil bahwa pemanfaatan Senayan Library Management System (SLiMS) di Kantor Perpustakaan dan Arsip Daerah Kota Salatiga telah memenuhi dua aspek utama dalam teori Technology Acceptance Model (TAM). SLiMS dinilai bermanfaat untuk membantu pekerjaan di perpustakaan termasuk untuk membantu pemustaka dalam proses penelusuran informasi. Dari penelitian ini diketahui pula bahwa pemanfaatan SLiMS belum maksimal dan masih dapat ditingkatkan dengan mengaktifkan visitor counter dan penggunaan fitur copy cataloging yang akan menambah manfaat dari SLiMS. SLiMS juga perangkat lunak yang mudah, baik dalam hal instalasi dan modifikasi serta mudah dalam hal pemakaian akan tetapi masih perlu adanya usaha untuk meningkatkan kemampuan pengguna untuk memanfaatkan SLiMS

Cold-Water Coral in Aquaria: Advances and Challenges. A Focus on the Mediterranean

Knowledge on basic biological functions of organisms is essential to understand not only the role they play in the ecosystems but also to manage and protect their populations. The study of biological processes, such as growth, reproduction and physiology, which can be approached in situ or by collecting specimens and rearing them in aquaria, is particularly challenging for deep-sea organisms like cold-water corals. Field experimental work and monitoring of deep-sea populations is still a chimera. Only a handful of research institutes or companies has been able to install in situ marine observatories in the Mediterranean Sea or elsewhere, which facilitate a continuous monitoring of deep-sea ecosystems. Hence, today’s best way to obtain basic biological information on these organisms is (1) working with collected samples and analysing them post-mortem and / or (2) cultivating corals in aquaria in order to monitor biological processes and investigate coral behaviour and physiological responses under different experimental treatments. The first challenging aspect is the collection process, which implies the use of oceanographic research vessels in most occasions since these organisms inhabit areas between ca. 150 m to more than 1000 m depth, and specific sampling gears. The next challenge is the maintenance of the animals on board (in situations where cruises may take weeks) and their transport to home laboratories. Maintenance in the home laboratories is also extremely challenging since special conditions and set-ups are needed to conduct experimental studies to obtain information on the biological processes of these animals. The complexity of the natural environment from which the corals were collected cannot be exactly replicated within the laboratory setting; a fact which has led some researchers to question the validity of work and conclusions drawn from such undertakings. It is evident that aquaria experiments cannot perfectly reflect the real environmental and trophic conditions where these organisms occur, but: (1) in most cases we do not have the possibility to obtain equivalent in situ information and (2) even with limitations, they produce relevant information about the biological limits of the species, which is especially valuable when considering potential future climate change scenarios. This chapter includes many contributions from different authors and is envisioned as both to be a practical “handbook” for conducting cold-water coral aquaria work, whilst at the same time offering an overview on the cold-water coral research conducted in Mediterranean laboratories equipped with aquaria infrastructure. Experiences from Atlantic and Pacific laboratories with extensive experience with cold-water coral work have also contributed to this chapter, as their procedures are valuable to any researcher interested in conducting experimental work with cold-water corals in aquaria. It was impossible to include contributions from all laboratories in the world currently working experimentally with cold-water corals in the laboratory, but at the conclusion of the chapter we attempt, to our best of our knowledge, to supply a list of several laboratories with operational cold-water coral aquaria facilities