Disruption of somatosensory cortex impairs motor learning and retention.

This study tests for a function of the somatosensory cortex, that, in addition to its role in processing somatic afferent information, somatosensory cortex contributes both to motor learning and the stabilization of motor memory. Continuous theta-burst magnetic stimulation (cTBS) was applied, before force-field training to disrupt activity in either the primary somatosensory cortex, primary motor cortex, or a control zone over the occipital lobe. Tests for retention and relearning were conducted after a 24 h delay. Analysis of movement kinematic measures and force-channel trials found that cTBS to somatosensory cortex disrupted both learning and subsequent retention, whereas cTBS to motor cortex had little effect on learning but possibly impaired retention. Basic movement variables are unaffected by cTBS suggesting that the stimulation does not interfere with movement but instead disrupts changes in the cortex that are necessary for learning. In all experimental conditions, relearning in an abruptly introduced force field, which followed retention testing, showed extensive savings, which is consistent with previous work suggesting that more cognitive aspects of learning and retention are not dependent on either of the cortical zones under test. Taken together, the findings are consistent with the idea that motor learning is dependent on learning-related activity in the somatosensory cortex.NEW & NOTEWORTHY This study uses noninvasive transcranial magnetic stimulation to test the contribution of somatosensory and motor cortex to human motor learning and retention. Continuous theta-burst stimulation is applied before learning; participants return 24 h later to assess retention. Disruption of the somatosensory cortex is found to impair both learning and retention, whereas disruption of the motor cortex has no effect on learning. The findings are consistent with the idea that motor learning is dependent upon learning-related plasticity in somatosensory cortex.

Differential distribution of N- and O-Glycans and variable expression of sialyl-T antigen on HeLa cells-Revealed by direct fluorescent glycan imaging.

Cells are covered with glycans. The expression and distribution of specific glycans on the surface of a cell are important for various cellular functions. Imaging these glycans is essential to aid elucidation of their biological roles. Here, utilizing methods of direct fluorescent glycan imaging, in which fluorescent sialic acids are directly incorporated into substrate glycans via recombinant sialyltranferases, we report the differential distribution of N- and O-glycans and variable expression of sialyl-T antigen on HeLa cells. While the expression of N-glycans tends to be more peripheral at positions where cell-cell interaction occurs, O-glycan expression is more granular but relatively evenly distributed on positive cells. While N-glycans are expressed on all cells, sialyl-T antigen expression exhibits a wide spectrum of variation with some cells being strongly positive and some cells being almost completely negative. The differential distribution of N- and O-glycans on cell surface reflects their distinctive roles in cell biology.

Somatosensory cortex participates in the consolidation of human motor memory.

Newly learned motor skills are initially labile and then consolidated to permit retention. The circuits that enable the consolidation of motor memories remain uncertain. Most work to date has focused on primary motor cortex, and although there is ample evidence of learning-related plasticity in motor cortex, direct evidence for its involvement in memory consolidation is limited. Learning-related plasticity is also observed in somatosensory cortex, and accordingly, it may also be involved in memory consolidation. Here, by using transcranial magnetic stimulation (TMS) to block consolidation, we report the first direct evidence that plasticity in somatosensory cortex participates in the consolidation of motor memory. Participants made movements to targets while a robot applied forces to the hand to alter somatosensory feedback. Immediately following adaptation, continuous theta-burst transcranial magnetic stimulation (cTBS) was delivered to block retention; then, following a 24-hour delay, which would normally permit consolidation, we assessed whether there was an impairment. It was found that when mechanical loads were introduced gradually to engage implicit learning processes, suppression of somatosensory cortex following training almost entirely eliminated retention. In contrast, cTBS to motor cortex following learning had little effect on retention at all; retention following cTBS to motor cortex was not different than following sham TMS stimulation. We confirmed that cTBS to somatosensory cortex interfered with normal sensory function and that it blocked motor memory consolidation and not the ability to retrieve a consolidated motor memory. In conclusion, the findings are consistent with the hypothesis that in adaptation learning, somatosensory cortex rather than motor cortex is involved in the consolidation of motor memory.

Direct fluorescent glycan labeling with recombinant sialyltransferases.

Glycosylation is a common modification found on numerous proteins and lipids. However, direct detection of glycans on these intact biomolecules has been challenge. Here, utilizing enzymatic incorporation of fluorophore-conjugated sialic acids, dubbed as direct fluorescent glycan labeling, we report the labeling and detection of N- and O-glycans on glycoproteins. The method allows detection of specific glycans without the laborious gel blotting and chemiluminescence reactions used in Western blotting. The method can also be used with a variety of fluorescent dyes.

Radiological assessment for bauxite mining and alumina refining.

OBJECTIVE: Two international benchmarks assess whether the mining and processing of ores containing Naturally Occurring Radioactive Material (NORM) require management under radiological regulations set by local jurisdictions. First, the 1 Bq/g benchmark for radionuclide head of chain activity concentration determines whether materials may be excluded from radiological regulation. Second, processes may be exempted from radiological regulation where occupational above-background exposures for members of the workforce do not exceed 1 mSv/year. This is also the upper-limit of exposure prescribed for members of the public. Alcoa of Australia Limited (Alcoa) has undertaken radiological evaluations of the mining and processing of bauxite from the Darling Range of Western Australia since the 1980s. Short-term monitoring projects have demonstrated that above-background exposures for workers do not exceed 1 mSv/year. A whole-of-year evaluation of above-background, occupational radiological doses for bauxite mining, alumina refining and residue operations was conducted during 2008/2009 as part of the Alcoa NORM Quality Assurance System (NQAS). The NQAS has been guided by publications from the International Commission on Radiological Protection (ICRP), the International Atomic Energy Agency (IAEA) and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). The NQAS has been developed specifically in response to implementation of the Australian National Directory on Radiation Protection (NDRP). METHODS: Positional monitoring was undertaken to increase the accuracy of natural background levels required for correction of occupational exposures. This is important in view of the small increments in exposure that occur in bauxite mining, alumina refining and residue operations relative to natural background. Positional monitoring was also undertaken to assess the potential for exposure in operating locations. Personal monitoring was undertaken to characterise exposures in Similar Exposure Groups (SEGs). The monitoring was undertaken over 12 months, to provide annual average assessments of above-background doses, thereby reducing temporal variations, especially for radon exposures. The monitoring program concentrated on gamma and radon exposures, rather than gross alpha exposures, as past studies have shown that gross alpha exposures from inhalable dust for most of the workforce are small in comparison to combined gamma and radon exposures. RESULTS: The natural background determinations were consistent with data in the literature for localities near Alcoa's mining, refining and residue operations in Western Australia, and also with UNSCEAR global data. Within the mining operations, there was further consistency between the above-background dose estimates and the local geochemistry, with slight elevation of dose levels in mining pits. Conservative estimates of above-background levels for the workforce have been made using an assumption of 100% occupancy (1920 hours per year) for the SEGs considered. Total incremental composite doses for individuals were clearly less than 1.0 mSv/year when gamma, radon progeny and gross alpha exposures were considered. This is despite the activity concentration of some materials being slightly higher than the benchmark of 1 Bq/g. CONCLUSIONS: The results are consistent with previous monitoring and demonstrate compliance with the 1 mSv/year exemption level within mining, refining and residue operations. These results will be of value to bauxite mines and alumina refineries elsewhere in the world.

Social status, risky health behaviors, and diabetes in middle-aged and older adults.

OBJECTIVE: This article investigates: (a) how social status influences diabetes prevalence and incidence; (b) how risky health behaviors contribute to the prediction of incident diabetes; (c) if the effects of health behaviors mediate the effects of social status on incident diabetes; and (d) if these effects differ in midlife and older age. METHODS: We examined nationally representative data from the 1992/1993-1998 panels of the Health and Retirement Study for middle-aged and older adults using logistic regression analyses. RESULT: The odds of prevalent diabetes were higher for people of older age, men, Black adults, and Latino adults. Higher early-life social status (e.g., parental schooling) and achieved social status (e.g., respondent schooling, economic resources) reduced the odds in both age groups. We observed similar patterns for incident diabetes in midlife but not in older age. Risky health behaviors--particularly obesity--increased the odds of incident diabetes in both age groups independent of social status. The increased odds of incident diabetes in midlife persisted for Black and Latino adults net of other social status factors. DISCUSSION: Risky health behaviors are key predictors of incident diabetes in both age groups. Economic resources also play an important protective role in incident diabetes in midlife but not in older age.

Outside and in: development of neuronal excitability.

Investigation of the development of excitability has revealed that cells are often specialized at early stages to generate Ca(2+) transients. Studies of excitability have converged on the central role of Ca(2+) and K(+) channels in the plasmalemma that regulate Ca(2+) influx and have identified critical functions for receptor-activated channels in the endoplasmic reticulum that allow efflux of Ca(2+) from intracellular stores. The parallels between excitability in these two locations motivate future work, because comparison of their properties identifies shared attributes.

Validity and reliability of diastolic pulse contour analysis (windkessel model) in humans.

The present study assessed (1) the impact of the measurement site (lower versus upper extremity) on the corresponding compliance variables and (2) the overall reliability of diastolic pulse contour (Windkessel-derived) analysis in normal and hypertensive subjects. Arterial tonograms were recorded in the supine position from the radial and posterior tibial arteries in 20 normotensive (116+/-12/68+/-8 mm Hg) and 27 essential hypertensive subjects (160+/-16/94+/-14 mm Hg). Ensemble-averaged data for each subject were fitted to a first-order lumped-parameter model (basic Windkessel) to compute whole-body arterial compliance (C(A)) and to a third-order lumped-parameter model (modified Windkessel) to compute proximal compliance (C(1)) and distal compliance (C(2)). Despite high-fidelity waveforms in each subject, the first-order Windkessel model did not yield interpretable (positive) values for C(A) in 50% of normotensives and 41% of hypertensives, whereas the third-order model failed to yield interpretable C(1) or C(2) results in 15% of normotensives and 41% of hypertensives. No between-site correlations were found for the first-order time constant, 2 of the 3 third-order model curve-fitting constants, or C(A), C(1), or C(2) (P>0.50). Mean values for all 3 compliance variables were higher for the leg than the arm (P<0.05 each). We conclude that differences in Windkessel-derived compliance values in the arm and leg invalidate whole-body model assumptions and suggest a strong influence of regional circulatory properties. The validity and utility of Windkessel-derived variables is further diminished by the absence of between-site correlations and the common occurrence of uninterpretable values in hypertensive subjects.

Genetic ablation of phosphatidylinositol transfer protein function in murine embryonic stem cells.

Phosphatidylinositol transfer proteins (PITPs) regulate the interface between signal transduction, membrane-trafficking, and lipid metabolic pathways in eukaryotic cells. The best characterized mammalian PITPs are PITP alpha and PITP beta, two highly homologous proteins that are encoded by distinct genes. Insights into PITP alpha and PITP beta function in mammalian systems have been gleaned exclusively from cell-free or permeabilized cell reconstitution and resolution studies. Herein, we report for the first time the use of genetic approaches to directly address the physiological functions of PITP alpha and PITP beta in murine cells. Contrary to expectations, we find that ablation of PITP alpha function in murine cells fails to compromise growth and has no significant consequence for bulk phospholipid metabolism. Moreover, the data show that PITP alpha does not play an obvious role in any of the cellular activities where it has been reconstituted as an essential stimulatory factor. These activities include protein trafficking through the constitutive secretory pathway, endocytic pathway function, biogenesis of mast cell dense core secretory granules, and the agonist-induced fusion of dense core secretory granules to the mast cell plasma membrane. Finally, the data demonstrate that PITP alpha-deficient cells not only retain their responsiveness to bulk growth factor stimulation but also retain their pluripotency. In contrast, we were unable to evict both PITP beta alleles from murine cells and show that PITP beta deficiency results in catastrophic failure early in murine embryonic development. We suggest that PITP beta is an essential housekeeping PITP in murine cells, whereas PITP alpha plays a far more specialized function in mammals than that indicated by in vitro systems that show PITP dependence.