Tenuous Tether

In mammalian cells, DNA methylation critically regulates gene expression and thus has pivotal roles in myriad of physiological and pathological processes. Here we report a novel method for targeted DNA demethylation using the widely used clustered regularly interspaced short palindromic repeat (CRISPR)-Cas system. Initially, modified single guide RNAs (sgRNAs) (sgRNA2.0) were constructed by inserting two copies of bacteriophage MS2 RNA elements into the conventional sgRNAs, which would facilitate the tethering of the Tet1 catalytic domain (Tet-CD), in fusion with dCas9 or MS2 coat proteins, to the targeted gene loci...

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While research has steadily begun to explore thoughts and beliefs linked with helplessness and despair in schizophrenia, it is less clearly understood how to account phenomenologically for the related experience of being unable to commit to action in the midst of grave discomfort. To explore this issue, the current paper presents an analysis of the experience of volitional paralysis of two persons over the course of long-term integrative psychotherapy. In particular, we explore the experience of the inability to commit to action and the consequences of the gradual recovery of a sense that one is capable of action...

Solid surfaces are modified by grafting poly(ethylene oxide), PEO, to influence their interaction with indwelling particles, in particular molecules of bovine serum albumin and human plasma proteins. As a rule, the grafted PEO layers suppress protein adsorption. The suppression is most effective when the PEO layer is in a molecular brush conformation having a reciprocal grafting density (area per grafted PEO chain) less than the dimensions of the protein molecules. Nevertheless, the protein molecules may penetrate the PEO brush to some extent...

Micromanipulation of the external bilayers of nonionic surfactant vesicles (niosomes) and liposomes allows the formation of tethers, which are fluid state lipid/surfactant lamellar nanotubes. The technique allows investigation of some of the factors affecting tether formation and vesicle-tether interactions. In this paper the movement of a vesicle along, or more precisely in, tethers derived from the vesicle, has been studied. When a vesicle is supported by bipolar tethers, stretching the tether on one side of the vesicle, initiates the movement of the vesicle in the opposite direction, at velocities ranging up to 2...

OBJECTIVE: We report our experience with a previously undescribed method of myelomeningocele closure, which is the use of bilateral lumbar periosteal flaps as an additional tissue layer in complex cases. These flaps reinforce the dural repair, act to protect the spinal cord, and may help to contain any potential cerebrospinal fluid leak from the primary repair of the cord, thereby preventing pseudomeningocele formation. METHODS: The repair involves the development of bilateral thoracolumbar fascial flaps in conjunction with periosteal flaps, which are elevated from adjacent lumbar pedicles and transverse processes, thus forming a composite tissue flap...

BACKGROUND: The early stages of apoptosis (programmed cell death) are said to be characterized by internucleosomal DNA fragmentation and "condensation of the cytoplasm" in which cells round up, detach, and increase in density. We studied the causation of apoptotic rounding. METHODS: Human Chang liver cells in normal monolayer culture were compared with apoptotic counterparts derived from serum growth factor deprivation. Cell-by-cell analysis using the Coulter EPICS PROFILE II flow cytometer studied 1) the cell cycle from propidium iodide-DNA bindings, 2) uptake of neutral red (NR) dye, a viable cell marker, and 3) cytosolic pH (pHi) modulations from 2',7'-bis(2-carboxyethyl)-5(and-6)-carboxyfluorescein (BCECF) fluorescence ratios with NH4Cl prepulsing and forward scatter bitmapping of cell surface area...