An ingestible wireless capsule for treatment of obesity.

Intragastric balloon has become a popular method for treatment of obesity due to its less-invasive and non-pharmaceutical procedure. In this method, a gas (or liquid)-filled balloon is inserted into the stomach using endoscopy or surgery. The balloon stays in and partially fills the stomach for a desired period of time to induce the feeling of satiety in the patient. At the end of the treatment period, the balloon is removed from the body using endoscopy or surgery. Although proven effective in treatment of obesity, this method suffers from several drawbacks. Requiring an endoscopic procedure or surgery to insert and exert the balloon from the stomach is the most important disadvantage of this method. These procedures are usually costly and may cause the patient to feel uncomfortable. Here, we propose a non-invasive method to overcome these drawbacks. In this method, an intragastric balloon is introduced into the body using an ingestible capsule. The volume of the capsule can be adjusted wirelessly after being swallowed by the patient. Using this method, a non-invasive and patient-specific treatment is possible.

EM measurements define the dimensions of the "30-nm" chromatin fiber: evidence for a compact, interdigitated structure.

Chromatin structure plays a fundamental role in the regulation of nuclear processes such as DNA transcription, replication, recombination, and repair. Despite considerable efforts during three decades, the structure of the 30-nm chromatin fiber remains controversial. To define fiber dimensions accurately, we have produced very long and regularly folded 30-nm fibers from in vitro reconstituted nucleosome arrays containing the linker histone and with increasing nucleosome repeat lengths (10 to 70 bp of linker DNA). EM measurements show that the dimensions of these fully folded fibers do not increase linearly with increasing linker length, a finding that is inconsistent with two-start helix models. Instead, we find that there are two distinct classes of fiber structure, both with unexpectedly high nucleosome density: arrays with 10 to 40 bp of linker DNA all produce fibers with a diameter of 33 nm and 11 nucleosomes per 11 nm, whereas arrays with 50 to 70 bp of linker DNA all produce 44-nm-wide fibers with 15 nucleosomes per 11 nm. Using the physical constraints imposed by these measurements, we have built a model in which tight nucleosome packing is achieved through the interdigitation of nucleosomes from adjacent helical gyres. Importantly, the model closely matches raw image projections of folded chromatin arrays recorded in the solution state by using electron cryo-microscopy.

A method for the in vitro reconstitution of a defined "30 nm" chromatin fibre containing stoichiometric amounts of the linker histone.

An understanding of the role of higher-order chromatin structure in the regulation of cellular processes such as transcription will require knowledge of the structure of the "30 nm" chromatin fibre and its folding and unfolding pathways. We report an in vitro chromatin reconstitution system, which uses arrays of 12 and 19 copies of a 200 bp repeat of the Widom 601 DNA sequence. Since this DNA sequence binds the histone octamer with much higher affinity than mixed sequence DNA, we have used competitor DNA in the reconstitutions to control the loading of both the histone octamer and linker histone onto the 601 DNA arrays. Using this method we have obtained nucleosome arrays that have one histone octamer and one H5 bound per 200 bp repeat, and hence have the stoichiometric composition of native chromatin. To obtain highly compact 30 nm chromatin fibres, we have investigated a number of folding buffer conditions including varying NaCl or MgCl(2) concentrations. Sedimentation velocity analysis shows that the reconstituted nucleosome arrays have the same folding properties as native chromatin and form highly compact structures in high NaCl concentrations or 1mM MgCl(2). Negative stain and electron cryo-microscopy of the folded arrays show a homogeneous population of folded particles with a uniform diameter of 34 nm. The data presented provide good evidence that the reconstitution method we have developed produces, for the first time, a defined population of folded 30 nm fibres suitable for detailed structural investigation.