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Reduced hippocampal activation during encoding and recognition of words in schizophrenia patients.

OBJECTIVE: In patients with schizophrenia, impaired hippocampal activation either during encoding or recognition tasks has been observed in a few functional imaging experiments. In this fMRI study, the authors report results of word encoding and recognition in schizophrenia patients and healthy comparison subjects, with a special focus on correcting for behavioral recognition success in order to prevent a bias related to lower task performance in the schizophrenia patients. METHOD: The verbal encoding and recognition tasks were both first analyzed irrespective of recognition success. In a second analysis, recognition success was included in the block-designed encoding task as a covariate of no interest, and incorrectly classified items were rejected from the analysis of the event-related recognition task. RESULTS: Patients performed poorer on the recognition task than the comparison subjects. Bilateral hippocampal activation during encoding and recognition was observed in both groups. Right hippocampal activation in patients during recognition became significant only after exclusion of wrongly classified items. Group comparison revealed greater activation in the healthy comparison subjects in the left anterior hippocampus during encoding and bilaterally during recognition. Greater bilateral hippocampal activation in the healthy subjects and greater activation in the right anterior hippocampus in the schizophrenic patients were revealed after presentation of novel words, which were intermixed with previously encoded words in the recognition task. After exclusion of incorrectly classified items, the differences in the right hippocampus remained significant. CONCLUSIONS: This study provides evidence for disturbed hippocampal function during verbal encoding and recognition in patients with schizophrenia. It extends previous studies by correcting for the possible confound of differences in behavioral task performance. This approach further supports the concept of hippocampal dysfunction in schizophrenia.

Adult↗

Ambiguous encoding of stimuli by primary sensory afferents causes a lack of independence in the perception of multiple stimulus attributes.

Accurate sensory perception often depends on the independent encoding and subsequent integration of multiple stimulus attributes. In the weakly electric fish Eigenmannia, P- and T-type primary afferent fibers are specialized for encoding the amplitude and phase, respectively, of electrosensory stimuli. We used a stimulus estimation technique to quantify the ability of P- and T-units to encode random modulations in amplitude and phase. As expected, P-units exhibited a clear preference for encoding amplitude modulations, whereas T-units exhibited a clear preference for encoding phase modulations. Surprisingly, both types of afferents also encoded their nonpreferred stimulus attribute when it was presented in isolation or when the preferred stimulus attribute was sufficiently weak. Because afferent activity can be affected by modulations in either amplitude or phase, it is not possible to unambiguously distinguish between these two stimulus attributes by observing the activity of a single afferent fiber. Simple model neurons with a preference for encoding either amplitude or phase also encoded their nonpreferred stimulus attribute when it was presented in isolation, suggesting that such ambiguity is unavoidable. Using the well known jamming avoidance response as a probe of electrosensory perception, we show that the ambiguity at the single-neuron level gives rise to a systematic misrepresentation of stimuli at the population level and a resulting misperception of the amplitude and phase of electrosensory stimuli.

Action Potentials↗

Changes in content of mRNA encoding oxytocin in the pig uterus during the oestrous cycle, pregnancy, at parturition and in lactational anoestrus.

The aim of this study was to show that the pig uterus synthesizes oxytocin. Uteri were obtained from 2-7 pigs at regular intervals during the oestrous cycle, throughout pregnancy, at parturition and in lactational anoestrus. Localization of mRNA encoding oxytocin was by in situ hybridization and oxytocin concentrations were measured by radioimmunoassay. As reproductive status changed, mRNA encoding oxytocin varied significantly (P < 0.05). Uterine tissue type was a significant factor in determining synthesis of mRNA encoding oxytocin (P < 0.001). In luminal epithelia, concentrations of mRNA encoding oxytocin were greater at oestrus than during day 14 of the luteal phase (P < 0.01) or at any stage of pregnancy (P < 0.05), with concentrations minimal at parturition. This trend was also exhibited in uterine circular muscle. In longitudinal muscle, concentrations of mRNA encoding oxytocin were lower during late pregnancy than at oestrus (P < 0.05) or during the luteal phase (P < 0.05). Concentrations were minimal at parturition. The oxytocin content in endometrial and myometrial tissue was positively correlated across reproductive status (P < 0.02, r = 0.402, n = 35). These data are the first indication that the uterine endometrium and musculature of the pig express mRNA encoding oxytocin. The luminal epithelium of animals at oestrus was particularly rich in mRNA encoding oxytocin, whilst late pregnant and parturient animals did not show a rise in mRNA encoding oxytocin. Local uterine synthesis of oxytocin may therefore be more important in control of the oestrous cycle than in pregnancy or at parturition in pigs.

Animals↗

Effects of luteotrophic and luteolytic hormones on expression of mRNA encoding insulin-like growth factor I and growth hormone receptor in the ovine corpus luteum.

The regulation of mRNAs encoding insulin-like growth factor I (IGF-I) and the receptor for growth hormone (GH-R) in ovine luteal tissue by luteotrophic and luteolytic hormones was examined. In Expt 1, ewes were hypophysectomized (HPX) on day 5 of the oestrous cycle and administered saline (S), LH, GH, or LH + GH until day 12 of the oestrous cycle (n = 4 ewes per group). Concentrations of luteal mRNA encoding IGF-I in HPX + S ewes and pituitary-intact ewes at day 5 (n = 4) were approximately 60% (P < 0.05) of those in pituitary-intact ewes at day 12 (n = 4). Treatment of HPX ewes with GH or GH + LH, but not LH alone, increased concentrations of mRNA encoding IGF-I to values similar to those in pituitary-intact ewes at day 12. Hypophysectomy also reduced the mean concentration of mRNA encoding GH-R to approximately 60% (P < 0.05) of the values in pituitary-intact ewes (days 5 or 12). Treatment with LH, but not GH, increased (P < 0.05) concentrations of mRNA encoding GH-R to values observed in pituitary-intact ewes. In Expt 2, prostaglandin F2 alpha (PGF2 alpha; 1 mumole) injected into the ovarian artery on day 11 or day 12 of the oestrous cycle had no effect on luteal concentrations of mRNA for either IGF-I or GH-R. In Expt 3, concentrations of mRNA encoding IGF-I increased (P < 0.05) between days 3 and 6 and remained high for the duration (days 9, 12 and 15) of the oestrous cycle while luteal concentrations of mRNA encoding GH-R did not change. In conclusion, responsiveness of the corpus luteum to GH and luteal synthesis of IGF-I are likely regulators of luteal development and function. However, PGF2 alpha-induced luteolysis was not associated with a decrease in concentrations of mRNAs encoding either IGF-I or GH-R.

Animals↗

Transcripts encoding HAND genes are differentially expressed and regulated by BMP4 and GDNF in developing avian gut.

Growth and transcription factors provide important developmental cues to neural crest-derived precursors of enteric neurons. The basic helix-loop-helix transcription factors, HAND2 and HAND1, are expressed in the gastrointestinal tract, but neither the growth factors that induce their expression nor the cell types that express them in the gut are known. We show that transcripts encoding HAND2 are expressed in all segments of the developing gut while those encoding HAND1 are confined to the small intestine and colon. Using in situ hybridization combined with immunostaining using cell type-specific antigens, we demonstrate that transcripts encoding HAND2 are expressed in neurons of both the myenteric and submucosal ganglia. Transcripts encoding HAND1 are expressed by cells in the epithelial lining of the small intestine and colon. The differential localization of HAND2 and HAND1 is reflected in nonoverlapping patterns of regulation by gut-derived factors. The expression of transcripts encoding HAND2 is increased in neural crest-derived cells when cocultured with E4 gut, suggesting a gut-derived factor regulates expression of HAND genes. Exposure of gut-derived neural crest-derived cells to BMP4 significantly increased the expression of HAND2 in all gut segments. In the esophagus and gizzard, where HAND1 is not normally expressed, treatment with BMP4 induced the expression of transcripts encoding HAND1 in nonneural crest-derived cells. GDNF failed to induce consistent expression of transcripts encoding HAND2 in neural crest cells but did support a modest increase in HAND2 expression in gut-derived crest cells obtained from the esophagus and colon. GDNF had no detectable effect on the expression of transcripts encoding HAND1. These results suggest; 1) that HAND2 has a function in the development of enteric neurons, and 2) that BMP and GDNF differentially regulate HAND2 and HAND1 gene expression in the developing gastrointestinal tract.

Animals↗

Linguistic encoding in short-term memory as a function of stimulus type.

In this study, we investigated bases for encoding linguistic stimuli in short-term memory. Past research has provided evidence for both phonological (sound-based) and cherological (sign-based) encoding, the former typically found with hearing subjects and the latter with deaf users of sign language. In the present experiment, encoding capabilities were delineated from encoding preferences, using 58 subjects comprising six groups differing in hearing ability and linguistic experience. Phonologically related, cherologically related, and control lists were presented orally, manually, or through both modalities simultaneously. Recall performance indicated that individuals encode flexibly, the code actually used being biased by incoming stimulus characteristics. Subjects with both sign and speech experience recalled simultaneous presentations better than ones presented orally or manually alone, which reveals the occurrence of enhanced encoding as a function of linguistic experience. Total linguistic experience appeared to determine recall accuracy following different types of encoding, rather than determining the encoding basis used.

Adult↗

[Duration of enhancement and scan timing in three-dimensional contrast-enhanced MR angiography using the elliptical centric phase-encoding technique].

In the present study, we quantitatively investigated the relationship between the signal intensity in a vessel and the duration of contrast enhancement as well as scan timing in 3D contrast-enhanced MR angiography using an elliptical centric phase-encoding technique. A tube phantom filled with Gd-DTPA, acting as a vessel, was taken out from the field of view during data acquisition, by using the "pause" function of our MR scanner (GE Signa, 1.5 Tesla), thereby simulating the presence and absence of a vessel. The shortening of the duration of enhancement corresponds to the delay of scan timing from the optimal point in the phase-encoding of the centric-ordering system. The signal intensity in a vessel (1-5 mm in diameter) decreased as the duration of enhancement became shorter and the diameter of the vessel decreased. When the number of partitions was 16 or 32 in a 128-mm-thick slab, the signal intensity obtained by the elliptical centric phase-encoding technique was almost the same as that obtained by the conventional centric phase-encoding technique. However, when the number of partitions was increased (64-124), and if the duration of enhancement was short, the signal intensity obtained by the elliptical centric phase-encoding technique was higher than that obtained by the conventional centric phase-encoding technique. In conclusion, in terms of the duration of enhancement and the delay of scan timing, the elliptical centric phase-encoding technique is superior to the conventional centric phase-encoding technique when the number of partitions in a slab for 3D MR angiography is increased.

Contrast Media↗

VH4-34 encoded antibody in systemic lupus erythematosus: effect of isotype.

OBJECTIVE: To determine the clinical significance of elevated serum levels of VH4-34 encoded IgM and IgG antibodies with respect to the clinical characteristics of systemic lupus erythematosus (SLE). METHODS: VH4-34 encoded IgM and IgG immunoglobulin was measured in 95 patients with SLE by ELISA using antiidiotype monoclonal antibody (Mab) 9G4. SLE disease activity, severity, and damage were assessed by visual analog scales, Systemic Lupus Activity Measure, Lupus Severity of Disease Index, and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Presence of VH4-34 encoded antibodies on patients' B lymphocytes was analyzed by flow cytometry using Mab 9G4. RESULTS: Fifty-two of 95 patients with SLE had elevated levels of VH4-34 encoded antibodies of IgG isotype; 17 patients with VH4-34 IgG had elevated VH4-34 of the IgM isotype. Forty-three of the 95 patients had normal levels of VH4-34 encoded antibodies. When disease severity was correlated to VH4-34 isotype, patients with circulating VH4-34 IgG but without IgM had significantly more severe disease compared to patients who had VH4-34 of both isotypes. Eighty-six percent of patients with SLE nephritis and 100% of those with central nervous system (CNS) lupus had VH4-34 IgG without IgM. In vivo, VH4-34 encoded antibodies were found to bind autologous B lymphocytes. CONCLUSION: Presence of VH4-34 IgG in the absence of VH4-34 IgM was the finding most strongly associated with severe SLE, nephritis, and CNS lupus, suggesting that isotype switching of VH4-34 encoded antibodies or loss of VH4-34 IgM encoded antibodies may influence the progression of disease in SLE.

Adult↗

Attentional resource demands of stimulus encoding for persons with and without mental retardation.

Speed of encoding differences between individuals with and without mental retardation were examined to determine whether they stem from an automatically executed cognitive process or from encoding processes that require attentional resources. In Experiment 1, encoding functions were generated for physical identity and name identity encoding while subjects retained a full memory load or half memory load. Size of memory load influenced encoding times for all subjects. However, the pattern of group differences suggested that subjects with mental retardation allocated fewer attentional resources to encoding, even though encoding may require more of their resources for efficient execution. These conclusions were supported in Experiment 2, in which resource allocation was assessed using response times to auditory probes placed at various locations in the semantic encoding and decision task.

Adolescent↗

Structure and mapping of the gene encoding mouse high affinity Fc gamma RI and chromosomal location of the human Fc gamma RI gene.

We describe the isolation and characterization of the gene encoding the mouse high affinity Fc receptor Fc gamma RI. Using a mouse cDNA Fc gamma RI probe four unique overlapping genomic clones were isolated and were found to encode the entire 9 kb of the mouse Fc gamma RI gene. Sequence analysis of the gene showed that six exons account for the entire Fc gamma RI cDNA sequences including the 5'- and 3'-untranslated sequences. The first and second exons encode the signal peptide; exons 3, 4, and 5 encode the extracellular Ig binding domains; and exon 6 encodes the transmembrane domain, the cytoplasmic region, and the entire 3'-untranslated sequence. This exon pattern is similar to Fc gamma RIII and Fc epsilon RI but differs from the related Fc gamma RII gene which contains 10 exons and encodes the b1 and b2 Fc gamma RII. Southern blot analysis had shown that the mouse Fc gamma RI gene is a single copy gene with no RFLP in inbred strains of mice, but analysis of an intersubspecies backcross of mice showed that unlike other mouse FcR genes which are on mouse chromosome 1 the locus encoding Fc gamma RI, termed Fcg1, is located on chromosome 3. Interestingly, the Fcg1 locus is located near the end of a region with known linkage homology to human chromosome 1. Analysis of human x rodent somatic cell hybrid cell lines indicates that the human FCG1 locus encoding the human Fc gamma RI maps to chromosome I and therefore possibly linked to other FcR genes on this chromosome. These results suggest that the linkage relationships among these genes in the human genome are not preserved in the mouse.

Amino Acid Sequence↗

Chloroplast and cytosolic glutamine synthetase are encoded by homologous nuclear genes which are differentially expressed in vivo.

We have shown that the individual members of the plant gene family for glutamine synthetase (GS) are differentially expressed in vivo, and each encode distinct GS polypeptides which are targeted to different subcellular compartments (chloroplast or cytosol). At the polypeptide level, chloroplast GS (GS2) and cytosolic GS (GS1 and GSn) are distinct and show an organ-specific distribution. We have characterized full length cDNA clones encoding chloroplast or cytosolic GS of pea. In vitro translation products encoded by three different GS cDNA clones, correspond to the mature GS2, GS1, and GSn polypeptides present in vivo. pGS185 encodes a precursor to the chloroplast GS2 polypeptide as shown by in vitro chloroplast uptake experiments. The pGS185 translation product is imported into the chloroplast stroma and processed to a polypeptide which corresponds in size and charge to that of mature chloroplast stromal GS2 (44 kDa). The 49 amino terminal amino acids encoded by pGS185 are designated as a chloroplast transit peptide by functionality in vitro, and amino acid homology to other transit peptides. The cytosolic forms of GS (GS1 and GSn) are encoded by highly homologous but distinct mRNAs. pGS299 encodes the cytosolic GS1 polypeptide (38 kDa), while pGS341 (Tingey, S. V., Walker, E. L., and Coruzzi, G. M. (1987) EMBO. J. 6, 1-9) encodes a cytosolic GSn polypeptide (37 kDa). The homologous nuclear genes for chloroplast and cytosolic GS show different patterns of expression in vivo. GS2 expression in leaves is modulated by light, at the level of steady state mRNA and protein, while the expression of cytosolic GS is unaffected by light. The light-induced expression of GS2 is due at least in part to a phytochrome mediated response. Nucleotide sequence analysis indicates that chloroplast and cytosolic GS have evolved from a common ancestor and suggest a molecular mechanism for chloroplast evolution.

Amino Acid Sequence↗

The plastocyanin-deficient phenotype of Chlamydomonas reinhardtii Ac-208 results from a frame-shift mutation in the nuclear gene encoding preapoplastocyanin.

Ac-208 is a plastocyanin-deficient mutant of Chlamydomonas reinhardtii that contains only 2-3% of the wild-type level of plastocyanin-encoding mRNA and no detectable plastocyanin. Sequence analysis of the ac-208 plastocyanin-encoding gene reveals a single nucleotide insertion in the first exon compared with the wild-type gene; this alters the reading frame and results in a premature nonsense codon. We have introduced the genomic sequence encoding plastocyanin from a wild-type strain into ac-208 by cotransformation with a selectable marker encoding nitrate reductase. Of 22 nit+ transformants characterized, nine contained additional plastocyanin-encoding sequences (compared with untransformed cells) and each of these nine transformants was found to accumulate the protein. Transformants that do not contain newly introduced plastocyanin sequences retain the plastocyanin-deficient phenotype. The introduced plastocyanin-encoding sequences are stable during mitotic growth in liquid culture over a period of several months, as is expression from the introduced sequences. We suggest that the decreased steady state level of plastocyanin-encoding messages is a consequence of the frame-shift mutation in the structural gene. The ability to complement ac-208 with plastocyanin-encoding sequences will allow the introduction and analysis of in vitro mutagenized plastocyanin sequences in vivo in transgenic C. reinhardtii cells.

Amino Acid Sequence↗

Automatic activation of the medial temporal lobe during encoding: lateralized influences of meaning and novelty.

In contrast to early failures, recent functional brain imaging studies have shown that medial temporal lobe (MTL) structures are active during performance of a variety of tasks. These studies have revealed three properties of the MTL that are consistent with its critical role in establishing new declarative memories. First, the MTL is automatically engaged whenever an event is experienced, with the side of activation (left, right) dependent on the nature of the material presented (verbal, nonverbal). Second, the strength or amount of activity depends on how well the material is encoded. Deep encoding will produce more MTL activity than shallow encoding. Depth of encoding-related increases in activity are more commonly seen on the left, because deep encoding is nearly always synonymous with encoding for meaning, and, therefore, depends on left-lateralized language mechanisms. Third, the amount of MTL activity depends on novelty. Unfamiliar events and contexts will produce more MTL activity than familiar events and contexts. Novelty-related increases are more commonly seen on the right, perhaps reflecting the greater role of the right hemisphere in maintaining tonic attention and arousal. These findings suggest a hemispheric division of labor involving encoding for meaning (left) and novelty detection (right), both of which lead to better remembering.

Arousal↗

Hippocampus as a memory map: synaptic plasticity and memory encoding by hippocampal neurons.

Hippocampal cells contribute to memory by rapidly encoding information about the perceptual and behavioral structure of experience. This paper describes two complementary experimental approaches that illustrate two important mechanisms that confer these properties to hippocampal cells: (1) Enduring spatial memory and stable place fields each depend upon synaptic plasticity mechanisms that normally rely on the same NMDA-receptor mediated metabolic events as long-term potentiation (LTP). Thus, hippocampal cells "learn" to encode information about the perceptual and behavioral structure of experiences. (2) Hippocampal cells encode the structure of experience and respond in a manner inconsistent with a spatial representation. Place fields are distributed heterogeneously in space, their locations are determined by non-geometric information, the population of active cells can indicate more than one location in space, and hippocampal cells encode discriminative stimuli independent of their spatial location. To the extent that the hippocampus encodes a map, it is more simply described as a memory map than a spatial map. Rather than computing spatial locations, the space it encodes is better described as a life or a problem space that encodes the history of experience into the relational structure of episodes.

Animals↗

Partial discrete Fourier transform (PDFT) multiband encoding.

For conventional multiband encoding techniques such as Hadamard encoding, scan time scales linearly with the number of slices encoded simultaneously. In this work, a new multiband encoding technique called partial discrete Fourier transform (PDFT) encoding is introduced, which overcomes this restriction. This technique incorporates the principle of partial Fourier imaging, allowing the tradeoff of SNR and imaging time without changing the number of slices. The theory behind PDFT encoding and its inherent sensitivity to phase errors are outlined. The theory was validated through simulations, showing that phase errors result in degraded slice localization. The feasibility of PDFT encoding of 12 slices was tested with experimental excitation profile measurements and heart images of a human subject using commercial MRI equipment. Imaging time was reduced to 66% with SNR reduced to 82%. Magn Reson Med 45:118-127, 2001.

Computer Simulation↗

Determination of plasmid-encoded functions in Rhizobium leguminosarum biovar trifolii using proteome analysis of plasmid-cured derivatives.

We have used proteome analysis of derivatives of R. leguminosarum biovar trifolii strain ANU843, cured of indigenous plasmids by a direct selection system, to investigate plasmid-encoded functions. Under the conditions used, the plasmid-encoded gene products contributed to only a small proportion of the 2000 proteins visualised in the two-dimensional (2-D) protein map of strain ANU843. The level of synthesis of thirty-nine proteins was affected after curing of either plasmid a, c or e. The differences observed upon plasmid curing included: protein loss, up/down-regulation of specific proteins and novel synthesis of some proteins. This suggests that a complex interplay between the cured plasmid and the remaining replicons is occurring. Twenty-two proteins appeared to be absent in the cured strains and these presumably are encoded by plasmid genes. Of these, a small heat shock protein, a cold shock protein, a hypothetical YTFG-29.7 kDa protein, and the alpha and beta subunits of the electron transfer flavoprotein were identified by N-terminal microsequencing and predicted to be encoded by plasmid e. Four of the sequenced proteins putatively encoded on plasmid e and two encoded on plasmid c were novel. In addition, curing of plasmid e and c consistently decreased the levels of 3-isopropylmalate dehydratase and malate dehydrogenase, respectively, suggesting that levels of these proteins may be influenced by plasmid-encoded functions. A protein with homology to 4-oxalocrotonate tautomerase, which is involved in the biodegradation of phenolic compounds, was found to be newly synthesised in the strain cured of plasmid e. Proteome analysis provides a sensitive tool to examine the functional organisation of the Rhizobium genome and the global gene interactions which occur between the different replicons.

Bacterial Proteins↗

Implementation of wavelet-encoded MR imaging.

Reconstructions of images from wavelet-encoded data are shown. The method of MR wavelet encoding in one dimension was proposed previously by Weaver and Healy. The technique relies on selective excitation with wavelet-shaped profiles generated by special radio-frequency waveforms. The result of the imaging sequence is a set of inner products of the image with orthogonal functions of the wavelet basis. Inversion of the wavelet data is accomplished with an efficient algorithm with processing times comparable with those of a fast Fourier transform. The experiments show that wavelet encoding by selective excitation of wavelet-shaped profiles is feasible. Wavelet-encoded images are compared with phase-encoded images that have a similar signal-to-noise ratio, and there is no discernible degradation in image quality due to the wavelet encoding. Potential benefits of wavelet encoding are briefly discussed.

Artifacts↗

Non-Fourier-encoded parallel MRI using multiple receiver coils.

This paper describes a general theoretical framework that combines non-Fourier (NF) spatially-encoded MRI with multichannel acquisition parallel MRI. The two spatial-encoding mechanisms are physically and analytically separable, which allows NF encoding to be expressed as complementary to the inherent encoding imposed by RF receiver coil sensitivities. Consequently, the number of NF spatial-encoding steps necessary to fully encode an FOV is reduced. Furthermore, by casting the FOV reduction of parallel imaging techniques as a dimensionality reduction of the k-space that is NF-encoded, one can obtain a speed-up of each digital NF spatial excitation in addition to accelerated imaging. Images acquired at speed-up factors of 2x to 8x with a four-element RF receiver coil array demonstrate the utility of this framework and the efficiency afforded by it.

Calibration↗