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Sleep-dependent learning and motor-skill complexity.

Learning of a procedural motor-skill task is known to progress through a series of unique memory stages. Performance initially improves during training, and continues to improve, without further rehearsal, across subsequent periods of sleep. Here, we investigate how this delayed sleep-dependent learning is affected when the task characteristics are varied across several degrees of difficulty, and whether this improvement differentially enhances individual transitions of the motor-sequence pattern being learned. We report that subjects show similar overnight improvements in speed whether learning a five-element unimanual sequence (17.7% improvement), a nine-element unimanual sequence (20.2%), or a five-element bimanual sequence (17.5%), but show markedly increased overnight improvement (28.9%) with a nine-element bimanual sequence. In addition, individual transitions within the motor-sequence pattern that appeared most difficult at the end of training showed a significant 17.8% increase in speed overnight, whereas those transitions that were performed most rapidly at the end of training showed only a non-significant 1.4% improvement. Together, these findings suggest that the sleep-dependent learning process selectively provides maximum benefit to motor-skill procedures that proved to be most difficult prior to sleep.

Adolescent↗

[Information characteristics of neuronal and synaptic plasticity].

Informational losses in neuronal nets(NN) with plastic elements were estimated. These losses are related with 1) transition from "complicated" decoding when from the modification state of such elements information of the whole set of recorded elements is extracted to "simple" decoding natural of NN functioning when information is extracted independently for individual events; 2) uncertainty concerning NN structure, if at decoding in one of the modification states the neuron reactivity totally or the weight of plastic synapse equals zero. After the transition from complicated to simple decoding these losses for gradual plasticity are so great that NN with such plasticity has no advantages in informational capacity as compared to the binary one. These losses are absent for plasticity of Olbus type. They are relatively high for neuronal plasticity of Hebb type. For Hebb synapses their value essentially depends on the net parameters.

Humans↗

PEBP2/CBF, the murine homolog of the human myeloid AML1 and PEBP2 beta/CBF beta proto-oncoproteins, regulates the murine myeloperoxidase and neutrophil elastase genes in immature myeloid cells.

The myeloperoxidase (MPO) and neutrophil elastase genes are expressed specifically in immature myeloid cells. The integrity of a polyomavirus enhancer core sequence, 5'-AACCACA-3', is critical to the activity of the murine MPO proximal enhancer. This element binds two species, myeloid nuclear factors 1 alpha and 1 beta (MyNF1 alpha and -beta), present in 32D cl3 myeloid cell nuclear extracts. The levels of the MyNF1s increase during early 32D cl3 cell granulocytic differentiation. Both MyNF1 alpha and -beta supershift with an antiserum raised by using a peptide derived from the N terminus of polyomavirus enhancer-binding protein 2/core-binding factor (PEBP2/CBF) alpha subunit. The specific peptide inhibits these supershifts. In vitro-translated PEBP2/CBF DNA-binding domain binds the murine MPO PEBP2/CBF site. An alternate PEBP2/CBF consensus site, 5'-GACCGCA-3', but not a simian virus 40 enhancer core sequence, 5'-TTCCACA-3', binds the MyNF1s in vitro and activates a minimal murine MPO-thymidine kinase promoter in vivo. The murine neutrophil elastase gene 100-bp 5'-flanking sequences contain several functional elements, including potential binding sites for PU.1, C/EBP, c-Myb, and PEBP2/CBF. The functional element 5'-GGCCACA-3' located at positions -66 to 72 differs from the PEBP2/CBF consensus (5'-PuACCPuCA-3') only by an A-to-G transition at position 2. This DNA element binds MyNF1 alpha and -beta weakly. The N terminis of two PEBP2/CBF alpha subunit family members, PEBP2 alpha A and PEBP2 alpha B (murine AML1), are nearly identical, and 32D c13 cl3 cells contain both corresponding mRNAs. Since t(8;21), t(3;21), and inv(16), associated with myeloid leukemias, disrupt subunits of PEBP2/CBF, we speculate that the resulting oncoproteins, AML1-ETO, AML1-EAP, AML1-Evi1, and CBF beta-MYH11, inhibit early myeloid differentiation.

Animals↗

A complex array of Hpr consensus DNA recognition sequences proximal to the enterotoxin gene in Clostridium perfringens type A.

Enterotoxin production in Clostridium perfringens is both strain dependent and sporulation associated. Underlying these phenotypic observations must lie a genetic and molecular explanation and the principal keys will be held within the DNA sequence both upstream and downstream of the structural gene cpe. In accordance with the above we have sequenced 4.1 kbp of DNA upstream of cpe in the type strain NCTC 8239. A region of DNA extending up to 1.5 kb 5' to cpe is conserved in all enterotoxin-positive strains. This region contains a putative ORF with substantial homology to an ORF in the Salmonella typhimurium IS200 insertion element and, in addition, contains multiple perfect consensus DNA-binding sequences for the Bacillus subtilis transition state regulator Hpr. The detailed structural elements revealed by the sequence analysis are presented and used to develop a new perspective on the molecular basis of enterotoxin production in this important food-poisoning bacterium.

Base Sequence↗

The GABAA receptor alpha 1 subunit Pro174-Asp191 segment is involved in GABA binding and channel gating.

The GABA-binding site undergoes structural rearrangements during the transition from agonist binding to channel opening. To define possible roles of the GABA(A) receptor alpha(1) subunit Pro(174)-Asp(191) segment in these processes, we used the substituted cysteine accessibility method to characterize this region. Each residue was individually mutated to cysteine, expressed with wild-type beta(2) subunits in Xenopus laevis oocytes, and examined using two-electrode voltage clamp. Most mutations did not alter GABA EC(50) values. The D183C mutation produced a 7-fold reduction in GABA sensitivity. There were no significant changes in the K(I) values for the competitive antagonist, SR-95531. N-Biotinylaminoethyl methanethiosulfonate modified P174C-, R176C-, S177C-, V178C-, V180C-, A181C-, D183C-, R186C- and N188C-containing receptors. The pattern of accessibility suggests that this protein segment is aqueous-exposed and adopts a random coil conformation. Both GABA and SR-95531 slowed covalent modification of V178C, V180C, and D183C, indicating that these residues may line the GABA-binding site. Further, pentobarbital-induced channel activation accelerated modification of V180C and A181C and slowed the modification of R186C, suggesting that this region of the alpha(1) subunit may act as a dynamic element during channel-gating transitions.

Amino Acid Sequence↗

Metastatic metaplastic carcinoma of the breast (MCB): an uncharacteristic pattern of presentation with clinicopathologic correlation.

Metaplastic carcinoma of the breast (MCB) is a well recognized but uncommon aberrant manifestation of poorly differentiated invasive carcinoma containing both epithelial (ductal) and mesenchymal elements as well as a transitional form between them. This heterogeneous tumor characteristically contains ductal carcinoma cells mixed with areas of diverse morphologic phenotype displaying spindle, squamous, chondroid, or osseous differentiation. Some studies have suggested that certain types of metaplastic carcinoma have a more favorable prognosis as compared with others. We describe a case involving a 67-yr-old woman who presented with metastatic nodules in the lungs and a vague but recent history of breast cancer. The case highlights a subtype of MCB with a predominant spindle cell component metastatic to the lung. Fine-needle aspiration biopsy (FNAB) smears of the nodules revealed a bland, spindle cell, mesenchymal proliferation with minimal evidence of an epithelial component. A second primary was clinically excluded and a request for review of the original slides identified a metaplastic component to the original tumor with a histologic and immunohistochemical profile identical to the metastatic tumor, confirming origin from the breast. Metaplastic carcinomas of the breast commonly bypass axillary lymph nodes and present as distant metastases. FNAB diagnosis of metaplastic carcinoma of the breast is quite difficult at the primary site and poses a formidable diagnostic challenge at a metastatic site, especially when the dominant pattern is not of the usual type. The literature is reviewed, confirming the rarity of such a presentation and the novelty of this case. Confirmation by FNAB is also quite difficult but may become more commonplace as a trend toward minimal intervention continues to gain popularity. This case emphasizes the importance of recognizing and reporting metaplastic elements in primary breast tumors, as well as the value of direct morphologic comparison of cytologic material from FNABs with archival histologic material. In such situations, the importance of complete and accurate clinicopathologic information is underscored.

Aged↗

Identification of tumor markers in models of human colorectal cancer using a 19,200-element complementary DNA microarray.

Metastasis represents a crucial transition in disease development and progression and has a profound impact on survival for a wide variety of cancers. Cell line models of metastasis have played an important role in developing our understanding of the metastatic process. We used a 19,200-element human cDNA microarray to profile transcription in three paired cell-line models of colorectal tumor metastasis. By correlating expression patterns across these cell lines, we have identified 176 genes that appear to be differentially expressed (greater than 2-fold) in all highly metastatic cell lines relative to their reference. An analysis of these genes reiterates much of our understanding of the metastatic process and suggests additional genes, many of previously uncharacterized function, that may be causatively involved in, or at least prognostic of, metastasis. Northern analysis of a limited number of these genes validates the observed pattern of expression and suggests that further investigation and functional characterization of the identified genes is warranted.

Biomarkers, Tumor↗

Structure and complex twinning of dysprosium disilicate (Dy2Si2O7), type B

Dysprosium disilicate (Dy(2)Si(2)O(7)) is triclinic with a = 6.6158 (2), b = 6.6604 (2), c = 12.0551 (4) A, alpha = 94.373 (2), beta = 90.836 (2), gamma = 91.512 (2) degrees, V = 529.4 (1) A(3), space group P1;, Z = 4 and D(x) = 6.156 g cm(-3). The structure (single-crystal X-ray, R = 0.033, wR = 0.041) is built from a linear triple tetrahedral group [Si(3)O(10)] and isolated [SiO(4)] tetrahedron cross-linked by Dy(3+) in one sixfold and three eightfold coordinated positions, and corresponds to the presently revised type B structure of Ho(2)Si(2)O(7). The formation of the unusual linear triple tetrahedral group in the type B structure allows for a more continuous transition in the mean size of REE(3+)O(n) (REE = rare earth element) polyhedra in REE disilicates through the 4f transition metal series. The crystal of Dy(2)Si(2)O(7) investigated was complexly twinned such that the diffraction pattern was also consistent with a larger dimensionally monoclinic unit cell (a = 22.5354, b = 14.2102, c = 6.6158 A, beta = 91.788 degrees ), which resulted in an apparent superstructure of the type B structure in space group C1;. Lattice coincidence with the type B unit cell appears to have been maintained during crystal synthesis and quenching by the complex sector-zoned growth twin.

Journal Article↗

[Granulocyte colony-stimulating factor producing lung large cell carcinoma with sarcomatous transformation].

We report a case of granulocyte colony-stimulating factor (G-CSF) producing lung large cell carcinoma with sarcomatous transformation. A 57-year-old man was admitted for evaluation of an abnormal shadow near the right pulmonary hilus on chest X-ray film. Brush cytology specimen from right B6 disclosed large cell carcinoma. His clinical stage was already IIIB (T3N3M0) on admission, so we immediately administered chemotherapy and radiation therapy. However, the patient's condition gradually deteriorated and he died of respiratory failure. Although there was no evidence of infection throughout his clinical course, his peripheral white blood cell count gradually increased and reached 47,000/mm3 (neutrophils 96%) before death. Histological study of the autopsy specimen revealed that the primary tumor was composed of two different elements (large cell carcinoma and spindle cell sarcomatoid element). The spindle cell sarcomatoid element appeared to have arisen from sarcomatous transformation of carcinoma cells, because the transition margin of the carcinoma to the sarcomatoid element was smooth, and special and immunohistochemical staining of both elements showed the same properties. Moreover, immunohistochemical study with monoclonal antibody to human G-CSF, 4A6 clearly demonstrated granular staining of G-CSF in the cytoplasm of tumor cells.

Carcinoma↗

Calcium, phosphorus, and magnesium contents of human milk during early lactation.

Early milk samples from 102 American mothers were examined for Ca, P, and Mg contents in relation to stage of lactation, intake of prenatal mineral supplements, maternal age, parity, and previous history of lactation. A total of 415 samples were collected at three stages of lactation: early transitional (4-7 days postpartum); transitional (10-14 days postpartum); and mature (30-45 days postpartum). No diurnal variations in element concentrations were observed in representative samples of late evening (PM) and early morning (AM) feedings collected during the transitional and mature stages. The mean concentrations for the major elements were highest in early transitional milk and in some cases decreased significantly (p less than 0.05) as lactation progressed. Ca, P, and Mg contents (means +/- SEM) were 26.3 +/- 0.6, 14.6 +/- 0.4, 5.3 +/- 0.1 mg/100 g in early transitional milk and 26.2 +/- 0.5, 13.3 +/- 0.3, and 5.0 +/- 0.1 in mature milk, respectively. Increasing uniformity in the elemental content of milk was noted among the mothers as lactation became established. No significant relationship was found between intake of dietary supplements containing Ca and Mg and levels of these elements in milk. Also, no significant correlations were found between maternal age, parity, or previous history of lactation and the elemental content of milk. From these data, it was estimated that fully breast-fed infants would receive approximately 33, 18, and 6.5 mg/kg/day of Ca, P, and Mg, respectively, during the neonatal period.

Calcium↗

Carcinosarcoma of the urinary bladder.

The clinical and pathologic features of three new and 35 previously reported carcinosarcomas of the urinary bladder were reviewed. This type of tumor is three times more common in men than women, and has occurred in patients from 33 to 82 years of age (average, 62 years), most of whom presented with hematuria of short duration. The tumors are usually large and polypoid, and on microscopic examination contain an intimate admixture of malignant epithelial and mesenchymal elements. The former may resemble transitional cell carcinoma, squamous cell carcinoma, adenocarcinoma or undifferentiated carcinoma; and the latter, fibrosarcoma, leiomyosarcoma, or undifferentiated sarcoma: skeletal muscle, osseous, and/or cartilaginous differentiation has occurred in from 25% to 50% of the tumors. Sixteen patients died as a result of their tumors; four others had metastatic disease and three were lost to follow-up. Twelve patients were alive and free of disease from 5 months to 7 years postoperatively. Most of the 12 underwent radical cystectomy, preceded in some cases by radiation therapy, but four underwent a more conservative operation.

Aged↗

Polyribosome dynamics: size-distribution as a function of attachment, translocation and release of ribosomes.

Assembly of polyribosomes is the ubiquitous manifestation of the activation of translational machinery in cells. This is accompanied by a concomitant appearance of mRNAs either from an activation of pre-existing ribo-nucleoprotein particles (RNP) or from newly synthesized transcripts. The size-distributions of polyribosomes as inferred from their sedimentation profiles are essentially defined by various kinetic parameters responsible for continuous flux of ribosomes due to their recycling between the "free" and the "bound" states. In the theoretical analysis presented here the time-evolution of polyribosomes and their sustenance in the steady state is considered as a Markovian process with the states of mRNAs defined as the number of ribosomes attached. Expressions for the elements of one-step transition matrix as a function of kinetic parameters related to the initiation, translocation and the release of ribosomes and the size of mRNA are derived. The latter is shown to be relevant only in so far as it sets an upper limit to the size of polyribosomes. Implications of transient arrest of ribosomes at the initiation site as envisaged in the signal hypothesis for the synthesis of secretory proteins and the putative role of receptor-mediated post-translational transport of proteins have been examined. Results of computer simulations on model systems have focussed attention on the diverse types of profiles that may appear under varying physiological conditions.

Animals↗

An epidemiological model of rinderpest. I. Description of the model.

The development of an epidemiological model of rinderpest in cattle and wildlife populations is described. The model uses a state-transition structure, incorporating a stochastic element through the use of Monte-Carlo methods modified to allow large populations to be simulated. The potential applications include the estimation of "safe" host population immunity rates and the design of cost-effective rinderpest vaccination programmes.

Animals↗

Quaternion representation of RNA sequences and tertiary structures.

A quaternion representation of nucleotides is proposed, with representation of RNA sequences by vectors whose elements are quaternions. Structure and transition matrices in quaternion representation are defined. Correspondence between diagrammatic technique in complex-number and quaternion representation of nucleotides is delineated.

Base Sequence↗

Severe hypercalcemia after transition from calcium carbonate to calcium citrate in an elderly woman treated with ergocalciferol 50,000 IU per day.

BACKGROUND: Absorption of calcium carbonate in the fasting state has been reported to be significantly compromised in subjects with achlorhydria. Although calcium carbonate malabsorption in the fasting state cannot be predicted, it might be corrected if the compound is administered with meals. However, administering calcium carbonate with meals is logistically challenging in long-term care facilities. OBJECTIVE: The aim of this study was to report the case of a woman who was transitioned to calcium citrate and subsequently experienced symptomatic severe hypercalcemia. METHODS: An 89-year-old female resident of the Wisconsin Veterans Home, a skilled nursing facility in King, Wisconsin, was receiving long-term treatment with ergocalciferol (vitamin D2) 50,000 IU/d. The patient also was receiving calcium carbonate supplements in the morning, and she rarely ate breakfast (fasting state). The patient was transitioned from 2000 mg/d of elemental calcium as carbonate to 1230 mg/d as citrate. RESULTS: After being switched from calcium carbonate to calcium citrate, the patient developed severe symptomatic hypercalcemia (16.8 mg/dL), the primary cause of which was the administration of an inappropriately high dose of vitamin D. CONCLUSIONS: We report a case of symptomatic severe hypercalcemia in a skilled nursing facility resident treated with an inappropriately high daily dose of vitamin D. Hypercalcemia manifested when calcium carbonate was replaced with calcium citrate.

Aged, 80 and over↗

Death and decay in the trees of Mango (Mangifera indica L.).

Death and decay of trees of Mango (Mangifera indica L.) var. Kesar due to fungal infection was studied histologically. Fungal infection in the trees was observed due to various reasons like mechanical injuries in the stem, pruning of the branches, through the inflorescences, attack of Ambrosia beetle and termites. In the initial stage, fungal spores get settled on the flowers due to presence of nectar, followed by their germination and entry of the hypha into peduncle, which gradually spreads into younger branches. The inflorescences were first attacked by Fusarium moniliformis followed by other fungi like Alternaria, Chetomium sp., Aspregillus ellipticus, Aspregillus niger, etc. Fungal mycelia gradually invade the xylem tissues from the top of the branches and spread basipetally ultimately causing death of the infected branches. During monsoon, the crevices on the surface of bark of the healthy plants supported the growth of fungi like Pleurotus, Auricularia, Xyleria, Daldinia sp., and Polyporous sp. The removal of bark from such infected trees revealed minute holes on the surface of the woody cylinder made by Ambrosia beetles. During wet season fungal mycelia makes an easy entry into the xylem through the wounded portion of the stem or pruned branches. Initial entry of the hyphae into xylem was seen through the ray cells. Then the hyphae enter into the lumen of axial elements lining the ray cells through pits and intracellular spaces. The vessel elements located in the xylem (transition zone) between healthy and infected portion were filled with tyloses while axial and ray parenchyma showed heavy accumulation of tannin contents. On the other hand, the infected xylem was also found devoid of reserve metabolites while in normal trees, axial and ray parenchyma showed heavy accumulation of starch grains.

Animals↗

Ultra-short columns for low-pressure ion chromatography.

Since the development of low-pressure ion chromatography (LPIC), many inorganic cations and anions as well as organic acids could be analyzed at a low-pressure of 1.96 x 10(5)-2.94 x 10(5) Pa. And the ultra-short columns took the place of the common long chromatographic columns. Furthermore, the ultra-short columns of LPIC not only reduced the system pressure appreciably, but also achieved high sensitivity and precision. In order to assess the characteristics of the super-short columns, much analysis, i.e., the analysis of alkali metals, alkaline earth metals, transition-metals, rare-earth elements, inorganic anions and organic acids as well as the common amino acids, were conducted. Moreover, excellent results were obtained from the LPIC columns.

Chromatography, Liquid↗