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PubMed1996

Myelin basic protein gene expression in neurons: developmental and regional changes in protein targeting within neuronal nuclei, cell bodies, and processes.

The myelin basic protein (MBP) gene is part of the golli-mbp gene complex. In mouse, the golli-mbp gene produces two families of mRNAs from different transcription start sites that generate either MBPs or golli proteins (which contain MBP sequences in addition to unique peptide sequences). In situ hybridization and immunocytochemical analyses indicate that golli products are expressed in selected neuronal populations in postnatal mouse brain, in addition to oligodendrocytes, as shown earlier. The principal subcellular location of golli proteins in neurons was in axonal and dendritic processes. In a small subset of neurons, golli proteins were located in nuclei. With development and neuronal maturation, golli-mbp expression decreased and/or there was a striking shift in subcellular localization from nuclei and cell soma to the cell processes in specific neuronal populations. Golli protein was localize in neurites of migrating cerebellar granule cells, but it shifted to a nuclear localization when the cells took up residence in the internal granule cell layer. In some regions, (e.g., olfactory bulb and cerebellum) golli proteins were expressed over the entire postnatal period examined (birth to 75 d). The unique patterns of developmental expression within individual populations of neurons, and the unusual shift in subcellular localization of golli proteins with neuronal migration and maturation, suggest a complex regulation of this gene at both the transcriptional and posttranslational levels. The data also suggest that the cellular function(s) of the golli proteins is very different from the structurally related MBPs.

Animals↗
PubMedDate not supplied

[The effect of reflex muscle massage on the body regulatory processes of peptic ulcer patients with concomitant diseases].

Compared to conventional treatment, the proposed method of deep reflex muscular massage for treatment of ulcer patients with associated diseases in combination with exercises for muscle strain, produce stronger positive changes in adaptive-compensatory systems. This may result in prolongation of the remission and in a decreased number of recurrences of ulcer and associated gastrointestinal diseases.

Adaptation, Physiological↗
PubMed2001

Protein refolding for industrial processes.

Inclusion body refolding processes are poised to play a major role in the production of recombinant proteins. Improving renaturation yields by minimizing aggregation and reducing chemical costs are key to the industrial implementation of these processes. Recent developments include solubilization methods that do not rely on high denaturant concentrations and the use of high hydrostatic pressure for simultaneous solubilization and renaturation.

Disulfides↗
PubMed2005

Linking out-of-body experience and self processing to mental own-body imagery at the temporoparietal junction.

The spatial unity of self and body is challenged by various philosophical considerations and several phenomena, perhaps most notoriously the "out-of-body experience" (OBE) during which one's visual perspective and one's self are experienced to have departed from their habitual position within one's body. Although researchers started examining isolated aspects of the self, the neurocognitive processes of OBEs have not been investigated experimentally to further our understanding of the self. With the use of evoked potential mapping, we show the selective activation of the temporoparietal junction (TPJ) at 330-400 ms after stimulus onset when healthy volunteers imagined themselves in the position and visual perspective that generally are reported by people experiencing spontaneous OBEs. Interference with the TPJ by transcranial magnetic stimulation (TMS) at this time impaired mental transformation of one's own body in healthy volunteers relative to TMS over a control site. No such TMS effect was observed for imagined spatial transformations of external objects, suggesting the selective implication of the TPJ in mental imagery of one's own body. Finally, in an epileptic patient with OBEs originating from the TPJ, we show partial activation of the seizure focus during mental transformations of her body and visual perspective mimicking her OBE perceptions. These results suggest that the TPJ is a crucial structure for the conscious experience of the normal self, mediating spatial unity of self and body, and also suggest that impaired processing at the TPJ may lead to pathological selves such as OBEs.

Adult↗
PubMed2003

Ultrasound biomicroscopy of pseudophakic eyes with chronic postoperative inflammation.

PURPOSE: To evaluate the ultrasound biomicroscopy (UBM) findings in pseudophakic eyes with chronic noninfectious postoperative inflammation and discuss the use of the technique in these cases. SETTING: Uveitis Service, Department of Ophthalmology, McGill University, Montréal, Québec, Canada. METHODS: Fifty-four eyes of 51 patients with chronic noninfectious postoperative inflammation were prospectively evaluated between January 1998 and September 2001. Patients with aphakia, a dislocated intraocular lens (IOL) in the posterior segment, and endophthalmitis were excluded. All patients had a UBM examination that comprised locating the IOL position, investigating the presence of lens remnants, and evaluating the anterior segment of the eye. RESULTS: Ultrasound biomicroscopic examination revealed IOL misplacement in 37 eyes (68.5%). Of these, 23 (62.2%) had a sulcus-implanted posterior chamber IOL (PC IOL), 9 (24.3%) an in-the-bag PC IOL, and 5 (13.5%) an anterior chamber IOL. Haptic misplacement was significantly higher with sulcus-implanted PC IOLs than with in-the-bag PC IOLs (P<.01). Other UBM findings included edematous ciliary body processes and hypoechogenic and/or thickened ciliary bodies in 11 eyes (20.4%), peripheral anterior synechias in 8 eyes (14.8%), a significant number of lens remnants (graded as severe) in 6 eyes (11.1%), a thick cyclitic membrane in 3 eyes (5.6%), and an early cyclitic membrane in 2 eyes (3.7%). CONCLUSIONS: Irritation of ocular tissues by an IOL was the main cause of chronic postoperative noninfectious inflammation in pseudophakic eyes. Therefore, detecting the IOL position and its relationships to ocular tissues is very important in planning the treatment. Ultrasound biomicroscopy is a practical method that accurately provides this information.

Adult↗
PubMed2004

Novel conserved domains in proteins with predicted roles in eukaryotic cell-cycle regulation, decapping and RNA stability.

BACKGROUND: The emergence of eukaryotes was characterized by the expansion and diversification of several ancient RNA-binding domains and the apparent de novo innovation of new RNA-binding domains. The identification of these RNA-binding domains may throw light on the emergence of eukaryote-specific systems of RNA metabolism. RESULTS: Using sensitive sequence profile searches, homology-based fold recognition and sequence-structure superpositions, we identified novel, divergent versions of the Sm domain in the Scd6p family of proteins. This family of Sm-related domains shares certain features of conventional Sm domains, which are required for binding RNA, in addition to possessing some unique conserved features. We also show that these proteins contain a second previously uncharacterized C-terminal domain, termed the FDF domain (after a conserved sequence motif in this domain). The FDF domain is also found in the fungal Dcp3p-like and the animal FLJ22128-like proteins, where it fused to a C-terminal domain of the YjeF-N domain family. In addition to the FDF domains, the FLJ22128-like proteins contain yet another divergent version of the Sm domain at their extreme N-terminus. We show that the YjeF-N domains represent a novel version of the Rossmann fold that has acquired a set of catalytic residues and structural features that distinguish them from the conventional dehydrogenases. CONCLUSIONS: Several lines of contextual information suggest that the Scd6p family and the Dcp3p-like proteins are conserved components of the eukaryotic RNA metabolism system. We propose that the novel domains reported here, namely the divergent versions of the Sm domain and the FDF domain may mediate specific RNA-protein and protein-protein interactions in cytoplasmic ribonucleoprotein complexes. More specifically, the protein complexes containing Sm-like domains of the Scd6p family are predicted to regulate the stability of mRNA encoding proteins involved in cell cycle progression and vesicular assembly. The Dcp3p and FLJ22128 proteins may localize to the cytoplasmic processing bodies and possibly catalyze a specific processing step in the decapping pathway. The explosive diversification of Sm domains appears to have played a role in the emergence of several uniquely eukaryotic ribonucleoprotein complexes, including those involved in decapping and mRNA stability.

Amino Acid Sequence↗
PubMed2006

Neural basis of embodiment: distinct contributions of temporoparietal junction and extrastriate body area.

Embodiment, the sense of being localized within one's physical body, is a fundamental aspect of the self. Recently, researchers have started to show that self and body processing require distinct brain mechanisms, suggesting two posterior brain regions as key loci: the temporoparietal junction (TPJ), which is involved in self processing and multisensory integration of body-related information; and the extrastriate body area (EBA), which responds selectively to human bodies and body parts. Here we used evoked potential mapping and a distributed linear inverse solution to show that activations in EBA and TPJ code differentially for embodiment and self location, because the location and timing of brain activation depended on whether mental imagery is performed with mentally embodied (EBA) or disembodied (TPJ) self location. In a second experiment, we showed that only EBA activation, related to embodied self location, but not TPJ activation, related to disembodied self location, was modified by the subjects' body position during task performance (supine or sitting). This suggests that embodied self location and actual body location share neural mechanisms. Collectively, these data show that distributed brain activity at the EBA and TPJ as well as their timing are crucial for the coding of the self as embodied and as spatially situated within the human body.

Adult↗
PubMed2005

A role for the eIF4E-binding protein 4E-T in P-body formation and mRNA decay.

4E-transporter (4E-T) is one of several proteins that bind the mRNA 5'cap-binding protein, eukaryotic initiation factor 4E (eIF4E), through a conserved binding motif. We previously showed that 4E-T is a nucleocytoplasmic shuttling protein, which mediates the import of eIF4E into the nucleus. At steady state, 4E-T is predominantly cytoplasmic and is concentrated in bodies that conspicuously resemble the recently described processing bodies (P-bodies), which are believed to be sites of mRNA decay. In this paper, we demonstrate that 4E-T colocalizes with mRNA decapping factors in bona fide P-bodies. Moreover, 4E-T controls mRNA half-life, because its depletion from cells using short interfering RNA increases mRNA stability. The 4E-T binding partner, eIF4E, also is localized in P-bodies. 4E-T interaction with eIF4E represses translation, which is believed to be a prerequisite for targeting of mRNAs to P-bodies. Collectively, these data suggest that 4E-T interaction with eIF4E is a priming event in inducing messenger ribonucleoprotein rearrangement and transition from translation to decay.

Blotting, Western↗
PubMed1976

[Basic changes in neurons in the peripheral regions of the human nervous system during pathologic processes (electron microscopic study)].

Compensatory-adaptational and reparative reactions were studied in bodies, processes, receptors and synapses of the human peripheral nervous system and in the innervated substrate (myocardium, kidney, liver) by means of electron microscopy. An extreme increase of the electron density of macromolecular protein formations of specific elementary particles was revealed, in particular, in the outer layers of the hypertrophid mitochondria cryst membranes at 50000.000 magnification. These particles are considered as mitochondria precursors.

Cell Nucleus↗
PubMed2002

Effect of operating variables on the yield of recombinant trypsinogen for a pulse-fed dilution-refolding reactor.

The inclusion body process route for manufacturing proteins offers distinct process advantages in terms of expression levels and the ease of initial inclusion body recovery. The efficiency of the refolding unit operation, however, does determine the overall economic feasibility of a process. Dilution refolding is the simplest and most extensively used refolding operation, although significant yield losses often occur due mainly to aggregation. Operating variables may have a significant effect on the degree of aggregation, but a systematic study has not been reported. This study investigates the effect of operating variables on the dilution refolding of solubilized r-trypsinogen inclusion bodies in a pulse-fed stirred reactor. Variables investigated were inclusion body washing, stirring speed, feed rate, concentration of solubilized r-trypsinogen, and concentration of urea during solubilization of the inclusion bodies. Additionally, the effect of baffles in the reactor was investigated. The yield of renatured r-trypsinogen varied between 12 +/- 0.2% and 21 +/- 1.0% depending on the specific combination of operating variables employed. It is clear that a suboptimal operating strategy can significantly reduce protein yield. In particular, we note that an increased intensity of mixing adversely affected yield in contrast to previous reports indicating that enhanced dispersion increases yield. We conclude that yield is determined not only by the efficiency of dispersion, but also by the local chemical environment of the protein as it folds, and the rate of change of this environment. This will be controlled by micromixing effects, and hence the intensity of agitation, in a complex manner requiring further characterization.

Bioreactors↗