A novel DAG-dependent mechanism links PKCa and Cyclin B1 regulating cell cycle progression

Through the years, different studies showed the involvement of Protein Kinase C (PKC) in cell cycle control, in particular during G1/S transition. Little is known about their role at G2/M checkpoint. In this study, using K562 human erythroleukemia cell line, we found a novel and specific mechanism through which the conventional isoform PKC� positively affects Cyclin B1 modulating G2/M progression of cell cycle. Since the kinase activity of this PKC isoform was not necessary in this process, we demonstrated that PKC�, physically interacting with Cyclin B1, avoided its degradation and stimulated its nuclear import at mitosis. Moreover, the process resulted to be strictly connected with the increase in nuclear diacylglycerol levels (DAG) at G2/M checkpoint, due to the activity of nuclear Phospholipase C β1 (PLCβ1), the only PLC isoform mainly localized in the nucleus of K562 cells. Taken together, our findings indicated a novel DAG dependent mechanism able to regulate the G2/M progression of the cell cycle

Renewable Energy Permitting Barriers in Hawaii: Experience from the Field

This white paper presents a summary of the solicited input from permitting agencies and renewable energy developers on the permitting process in Hawaii to provide stakeholders in Hawaii, particularly those involved in permitting, with information on current permitting barriers that renewable energy developers are experiencing

Basket Cases and Breadbaskets: Sacred Rice and Agricultural Development in Postcolonial Africa

Author's final manuscript.Based on ethnographic research among rural Diola in Guinea-Bissau, I provide a broad view of the history and interpenetration of rice in social, political, religious, and ecological domains, while chronicling the current difficulties of residents in this region who are no longer able to grown enough of it. These farmers’ experiences are unfolding at a time of revitalized attention to agricultural development in Africa, particularly under the auspices of the New Green Revolution for Africa. I examine the premises that constitute the resuscitated effort to address the plight of African farmers. I argue that the totalizing quality of rice in Diola and other rice-cultivating societies requires a development approach that takes into account dimensions of agrarian life not encapsulated by the high- modernist and anti-political orientation of the New Green Revolution for Africa

Spin-Peierls Dimerization of a s=1/2 Heisenberg Antiferromagnet on a Square Lattice

Dimerization of a spin-half Heisenberg antiferromagnet on a square lattice is investigated for several possible dimerized configurations, some of which are shown to have lower ground state energies than the others. In particular, the lattice deformations resulting in alternate stronger and weaker couplings along both the principal axes of a square lattice are shown to result in a larger gain in magnetic energy. In addition, a `columnar' configuration is shown to have a lower ground state energy and a faster increase in the energy gap parameter than a `staggered' configuration. The inclusion of unexpanded exchange coupling leads to a power law behaviour for the magnetic energy gain and energy gap, which is qualitatively different from that reported earlier. Instead of increasing as $\delta ^{x}$, the two quantities depend on $\delta$ as $\delta ^{\nu}/| \ln \delta | .$ This is true both in the near critical regime $(0\leq \delta \leq 0.1)$ as well as in the far regime $(0\leq \delta <1)$. It is suggested that the unexpanded exchange coupling is as much a source of the logarithmic dependence as a correction due to the contribution of umklapp processes. Staggered magnetization is shown to follow the same $\delta$-dependence in all the configurations in the small $\delta$-regime, while for $0\leq \delta <1$, it follows the power law $\delta ^{x}$.Comment: 12 pages, 7 Postscript figures, RevTex forma

Breast Milk Cytokines and Early Growth in Gambian Infants

Background: Breast milk provides nutrition for infants but also delivers other bioactive factors that have key protective and developmental benefits. In particular, cytokines are thought to play a role in immunomodulation, although little is known about their impact on health outcomes in early life. Objective: The purpose of this pilot study was to evaluate the relationship between cytokines in breast milk and infant growth outcomes in a low-income setting. Methods: 100 mother-infant pairs were followed up to 2–3 months postpartum as part of a prospective longitudinal cohort study in urban Gambia, West Africa. The concentrations of 9 pro-inflammatory cytokines (IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNFα), IGF-1 and TGFβ2 were measured in colostrum within 12 h of birth and in breast milk at the final visit, scheduled between day 60 and 89 postpartum. Infant weight was recorded and converted to weight-for-age Z-scores (WAZ) at the same time points. Growth outcomes were defined in our study as (a) change in WAZ between birth and final visit (b) WAZ at final visit. Linear regression analysis was used to determine the ability of colostrum and breast milk cytokine concentrations to predict growth outcomes up to 2–3 months postpartum. Results: Gambian infants demonstrated growth faltering across the first 2–3 months postpartum. There was no significant relationship between cytokines in colostrum and subsequent change in WAZ between birth and the final visit, in either unadjusted or adjusted models. However, cytokines in mature breast milk, TNFα, IFNγ, IL1β, IL2, IL4, and IL6, were weak negative predictors of WAZ scores at the final visit, in unadjusted models (p < 0.05). When adjusted for maternal anemia (as a proxy for maternal nutrition), TNFα and IL6 remained significant predictors (p < 0.05). Conclusions: Variations in breast milk cytokine levels do not play a substantial role in the growth faltering observed across early infancy. The potential contribution of other factors, such as micronutrients, hormones or human milk oligosaccharides, must be elucidated. Cytokine levels in mature breast milk were weakly predictive of poor infant growth, possibly reflecting a “read-out” of suboptimal maternal health and nutrition

Characterization and regulation of MT1‐MMP cell surface‐associated activity

Quantitative assessment of MT1‐MMP cell surface‐associated proteolytic activity remains undefined. Presently, MT1‐MMP was stably expressed and a cell‐based FRET assay developed to quantify activity toward synthetic collagen‐model triple‐helices. To estimate the importance of cell surface localization and specific structural domains on MT1‐MMP proteolysis, activity measurements were performed using a series of membrane‐anchored MT1‐MMP mutants and compared directly with those of soluble MT1‐MMP. MT1‐MMP activity (kcat/KM) on the cell surface was 4.8‐fold lower compared with soluble MT1‐MMP, with the effect largely manifested in kcat. Deletion of the MT1‐MMP cytoplasmic tail enhanced cell surface activity, with both kcat and KM values affected, while deletion of the hemopexin‐like domain negatively impacted KM and increased kcat. Overall, cell surface localization of MT1‐MMP restricts substrate binding and protein‐coupled motions (based on changes in both kcat and KM) for catalysis. Comparison of soluble and cell surface‐bound MT2‐MMP revealed 12.9‐fold lower activity on the cell surface. The cell‐based assay was utilized for small molecule and triple‐helical transition state analog MMP inhibitors, which were found to function similarly in solution and at the cell surface. These studies provide the first quantitative assessments of MT1‐MMP activity and inhibition in the native cellular environment of the enzyme.MT1‐MMP was stably expressed and a cell‐based FRET assay developed to quantify activity toward synthetic collagen‐model triple‐helices. Activity measurements were performed using a series of membrane‐anchored MT1‐MMP mutants and compared directly with those of soluble MT1‐MMP. Cell surface localization of MT1‐MMP was found to restrict substrate binding and protein‐coupled motions for catalysis. Small molecule and triple‐helical transition state analog MMP inhibitors were found to function similarly in solution and at the cell surface.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150520/1/cbdd13450.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150520/2/cbdd13450_am.pd

Production of π0 and η mesons in Cu+Au collisions at sNN =200 GeV

Production of π0 and η mesons has been measured at midrapidity in Cu+Au collisions at sNN=200GeV. Measurements were performed in π0(η)→γγ decay channel in the 1(2)-20GeV/c transverse momentum range. A strong suppression is observed for π0 and η meson production at high transverse momentum in central Cu+Au collisions relative to the p+p results scaled by the number of nucleon-nucleon collisions. In central collisions the suppression is similar to Au+Au with comparable nuclear overlap. The η/π0 ratio measured as a function of transverse momentum is consistent with mT-scaling parametrization down to pT=2GeV/c, its asymptotic value is constant and consistent with Au+Au and p+p and does not show any significant dependence on collision centrality. Similar results were obtained in hadron-hadron, hadron-nucleus, and nucleus-nucleus collisions as well as in e+e- collisions in a range of collision energies sNN=3-1800 GeV. This suggests that the quark-gluon-plasma medium produced in Cu+Cu collisions either does not affect the jet fragmentation into light mesons or it affects the π0 and η the same way

Spectrum and ionization rate of low energy Galactic cosmic rays

We consider the rate of ionization of diffuse and molecular clouds in the interstellar medium by Galactic cosmic rays (GCR) in order to constrain its low energy spectrum. We extrapolate the GCR spectrum obtained from PAMELA at high energies ($\ge 200$ GeV/ nucleon) and a recently derived GCR proton flux at $1\hbox{--}200$ GeV from observations of gamma rays from molecular clouds, and find that the observed average Galactic ionization rate can be reconciled with this GCR spectrum if there is a low energy cutoff for protons at $10\hbox{--}100$ MeV. We also identify the flattening below a few GeV as being due to (a) decrease of the diffusion coefficient and dominance of convective loss at low energy and (b) the expected break in energy spectrum for a constant spectral index in momentum. We show that the inferred CR proton spectrum of $\Phi \propto E_{kin}^{-1.7\pm0.2}$ for $E_{kin} \le$ few GeV, is consistent with a power-law spectrum in momentum $p^{-2.45\pm0.4}$, which we identify as the spectrum at source. Diffusion loss at higher energies then introduces a steepening by $E^{-\alpha}$ with $\alpha \sim 1/3$, making it consistent with high energy measurements.Comment: 5 pages, 3 figures, to appear in MNRAS Letter