Formation and Dissociation of Phosphorylated Peptide Radical Cations

published_or_final_versio

Fully Automatable Two-dimensional HILIC–RP Liquid Chromatography with Online Tandem Mass Spectrometry for Shotgun Proteomics

Poster PresentationConference theme: Proteomics: Better for lifeMultidimensional liquid chromatography (MDLC) which multiples the resolution power of individual dimension with high orthogonality is a very efficient front-end separation method for analyzing the digests of complex biological samples. Among the existing two dimensional liquid chromatography (2DLC) systems, the combination of hydrophilic interaction liquid chromatography (HILIC) followed by low-pH reversed-phase (RP)LC (HILIC-RP) has very high orthogonality and is a very promising 2DLC method. Herein, a fully automatable two-dimensional (2D) liquid chromatography system was developed for shotgun proteomics analyses, which coupling the hydrophilic interaction liquid chromatography (HILIC) TSKgel Amide 80 (a non-ionic type) with the low-pH reversedphase (RP) chromatography. The performance of the 2D HILIC-RP LC platform was investigated at both pH 6.8 (neutral pH) and pH 2.7 (acidic pH) of the first dimension HILIC column by duplicate analyses of a Rat pheochromocytoma lysates.Online coupling of the neutral-pH HILIC and RP systems outperformedthe acidic HILIC–RP combination,resulting in 18.4% (1914 versus 1617 nonredundant proteins) and 41.6% (12,989 versus 9172unique peptides) increases in the number of identified proteins and peptides. To further test the established 2D HILIC-RP platform, we identified 2648 non-redundant proteins from triplicate analyses of a Saccharomyces cerevisiae lysate, with the detected protein abundances spanning from approximately41 to 106 copies per cell, which contained up to 2164 different validated protein species with a dynamic range of concentrations up to approximately 104. Herein, this studyestablished a fully automated 2D liquid chromatography platform to enable onlinecoupling of different HILIC and RP chromatography systems, thereby expanding the choice and application of multidimensional liquid chromatography for shotgun proteomics.published_or_final_versio

Are old running shoes detrimental to your feet? A pedobarographic study

<p>Abstract</p> <p>Background</p> <p>Footwear characteristics have been implicated in fatigue and foot pain. The recommended time for changing running shoes is every 500 miles. The aim of our study was to assess and compare plantar peak pressures and pressure time integrals in new and old running shoes.</p> <p>Findings</p> <p>This was a prospective study involving 11 healthy female volunteers with no previous foot and ankle problems. New running shoes were provided to the participants. Plantar pressures were measured using the Novel Pedar system while walking with new and participants' personal old running shoes. Plantar pressures were measured in nine areas of the feet. Demographic data, age of old running shoes, Body Mass Index (BMI), peak pressures and pressure-time integral were acquired. The right and left feet were selected at random and assessed separately. Statistical analysis was done using the paired t test to compare measurements between old and new running shoes.</p> <p>The mean peak pressures were higher in new running shoes (330.5 ± 79.6 kiloPascals kPa) when compared to used old running shoes (304 ± 58.1 kPa) (p = 0.01). The pressure-time integral was significantly higher in the new running shoes (110 ± 28.3 kPa s) compared to used old running shoes (100.7 ± 24.0 kPa s) (p = 0.01).</p> <p>Conclusion</p> <p>Plantar pressure measurements in general were higher in new running shoes. This could be due to the lack of flexibility in new running shoes. The risk of injury to the foot and ankle would appear to be higher if running shoes are changed frequently. We recommend breaking into new running shoes slowly using them for mild physical activity.</p

Human Breast Milk and Antiretrovirals Dramatically Reduce Oral HIV-1 Transmission in BLT Humanized Mice

Currently, over 15% of new HIV infections occur in children. Breastfeeding is a major contributor to HIV infections in infants. This represents a major paradox in the field because in vitro, breast milk has been shown to have a strong inhibitory effect on HIV infectivity. However, this inhibitory effect has never been demonstrated in vivo. Here, we address this important paradox using the first humanized mouse model of oral HIV transmission. We established that reconstitution of the oral cavity and upper gastrointestinal (GI) tract of humanized bone marrow/liver/thymus (BLT) mice with human leukocytes, including the human cell types important for mucosal HIV transmission (i.e. dendritic cells, macrophages and CD4+ T cells), renders them susceptible to oral transmission of cell-free and cell-associated HIV. Oral transmission of HIV resulted in systemic infection of lymphoid and non-lymphoid tissues that is characterized by the presence of HIV RNA in plasma and a gradual decline of CD4+ T cells in peripheral blood. Consistent with infection of the oral cavity, we observed virus shedding into saliva. We then evaluated the role of human breast milk on oral HIV transmission. Our in vivo results demonstrate that breast milk has a strong inhibitory effect on oral transmission of both cell-free and cell-associated HIV. Finally, we evaluated the effect of antiretrovirals on oral transmission of HIV. Our results show that systemic antiretrovirals administered prior to exposure can efficiently prevent oral HIV transmission in BLT mice

Exploring the Higgs Portal with 10/fb at the LHC

We consider the impact of new exotic colored and/or charged matter interacting through the Higgs portal on Standard Model Higgs boson searches at the LHC. Such Higgs portal couplings can induce shifts in the effective Higgs-gluon-gluon and Higgs-photon-photon couplings, thus modifying the Higgs production and decay patterns. We consider two possible interpretations of the current LHC Higgs searches based on ~ 5/fb of data at each detector: 1) a Higgs boson in the mass range (124-126) GeV and 2) a `hidden' heavy Higgs boson which is underproduced due to the suppression of its gluon fusion production cross section. We first perform a model independent analysis of the allowed sizes of such shifts in light of the current LHC data. As a class of possible candidates for new physics which gives rise to such shifts, we investigate the effects of new scalar multiplets charged under the Standard Model gauge symmetries. We determine the scalar parameter space that is allowed by current LHC Higgs searches, and compare with complementary LHC searches that are sensitive to the direct production of colored scalar states.Comment: 27 pages, 11 figures; v2: references added, correction to scalar form factor, numerical results updated with Moriond 2012 data, conclusions unchange

Iterative solution to singular nth-order nonlocal boundary value problems

By using the cone theory and the Banach contraction mapping principle, we study the existence and uniqueness of an iterative solution to the singular nth-order nonlocal boundary value problems

Analysis of human meiotic recombination events with a parent-sibling tracing approach

<p>Abstract</p> <p>Background</p> <p>Meiotic recombination ensures that each child inherits distinct genetic materials from each parent, but the distribution of crossovers along meiotic chromosomes remains difficult to identify. In this study, we developed a parent-sibling tracing (PST) approach from previously reported methods to identify meiotic crossover sites of GEO GSE6754 data set. This approach requires only the single nucleotide polymorphism (SNP) data of the pedigrees of both parents and at least two of children.</p> <p>Results</p> <p>Compared to other SNP-based algorithms (identity by descent or pediSNP), fewer uninformative SNPs were derived with the use of PST. Analysis of a GEO GSE6754 data set containing 2,145 maternal and paternal meiotic events revealed that the pattern and distribution of paternal and maternal recombination sites vary along the chromosomes. Lower crossover rates near the centromeres were more prominent in males than in females. Based on analysis of repetitive sequences, we also showed that recombination hotspots are positively correlated with SINE/MIR repetitive elements and negatively correlated with LINE/L1 elements. The number of meiotic recombination events was positively correlated with the number of shorter tandem repeat sequences.</p> <p>Conclusions</p> <p>The advantages of the PST approach include the ability to use only two-generation pedigrees with two siblings and the ability to perform gender-specific analyses of repetitive elements and tandem repeat sequences while including fewer uninformative SNP regions in the results.</p

Plant Diversity Changes during the Postglacial in East Asia: Insights from Forest Refugia on Halla Volcano, Jeju Island

Understanding how past climate changes affected biodiversity is a key issue in contemporary ecology and conservation biology. These diversity changes are, however, difficult to reconstruct from paleoecological sources alone, because macrofossil and pollen records do not provide complete information about species assemblages. Ecologists therefore use information from modern analogues of past communities in order to get a better understanding of past diversity changes. Here we compare plant diversity, species traits and environment between late-glacial Abies, early-Holocene Quercus, and mid-Holocene warm-temperate Carpinus forest refugia on Jeju Island, Korea in order to provide insights into postglacial changes associated with their replacement. Based on detailed study of relict communities, we propose that the late-glacial open-canopy conifer forests in southern part of Korean Peninsula were rich in vascular plants, in particular of heliophilous herbs, whose dramatic decline was caused by the early Holocene invasion of dwarf bamboo into the understory of Quercus forests, followed by mid-Holocene expansion of strongly shading trees such as maple and hornbeam. This diversity loss was partly compensated in the Carpinus forests by an increase in shade-tolerant evergreen trees, shrubs and lianas. However, the pool of these species is much smaller than that of light-demanding herbs, and hence the total species richness is lower, both locally and in the whole area of the Carpinus and Quercus forests. The strongly shading tree species dominating in the hornbeam forests have higher leaf tissue N and P concentrations and smaller leaf dry matter content, which enhances litter decomposition and nutrient cycling and in turn favored the selection of highly competitive species in the shrub layer. This further reduced available light and caused almost complete disappearance of understory herbs, including dwarf bamboo

AP-PA field orientation followed by IMRT reduces lung exposure in comparison to conventional 3D conformal and sole IMRT in centrally located lung tumors

Little attention has been paid to the fact that intensity modulated radiation therapy (IMRT) techniques do not easily enable treatment with opposed beams. Three treatment plans (3 D conformal, IMRT, and combined (anterior-posterior-posterio-anterior (AP-PA) + IMRT) of 7 patients with centrally-located lung cancer were compared for exposure of lung, spinal cord and esophagus. Combined IMRT and AP-PA techniques offer better lung tissue sparing compared to plans predicated solely on IMRT for centrally-located lung tumors

New Insights into Human Nondisjunction of Chromosome 21 in Oocytes

Nondisjunction of chromosome 21 is the leading cause of Down syndrome. Two risk factors for maternal nondisjunction of chromosome 21 are increased maternal age and altered recombination. In order to provide further insight on mechanisms underlying nondisjunction, we examined the association between these two well established risk factors for chromosome 21 nondisjunction. In our approach, short tandem repeat markers along chromosome 21 were genotyped in DNA collected from individuals with free trisomy 21 and their parents. This information was used to determine the origin of the nondisjunction error and the maternal recombination profile. We analyzed 615 maternal meiosis I and 253 maternal meiosis II cases stratified by maternal age. The examination of meiosis II errors, the first of its type, suggests that the presence of a single exchange within the pericentromeric region of 21q interacts with maternal age-related risk factors. This observation could be explained in two general ways: 1) a pericentromeric exchange initiates or exacerbates the susceptibility to maternal age risk factors or 2) a pericentromeric exchange protects the bivalent against age-related risk factors allowing proper segregation of homologues at meiosis I, but not segregation of sisters at meiosis II. In contrast, analysis of maternal meiosis I errors indicates that a single telomeric exchange imposes the same risk for nondisjunction, irrespective of the age of the oocyte. Our results emphasize the fact that human nondisjunction is a multifactorial trait that must be dissected into its component parts to identify specific associated risk factors