Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Effect of pre-milking teat preparation procedures on the microbial count on teats prior to cluster application

A study was carried out to investigate the effect of six pre-milking teat preparation procedures on lowering the staphylococal, streptococcal and coliform microbial count on teat skin prior to cluster application. The teat preparations included 'Iodine', 'Chlorhexidine' teat foam, 'Washing and drying' with paper, 'No preparation', 'Chlorine' teat foam, and disinfectant 'Wipes'. Teat preparations were applied for five days to 10 cows for each treatment during two herd management periods (indoors and outdoors). Teats were swabbed on day four and five before teat preparation and repeated after teat preparation. The swabs were plated on three selective agars: Baird Parker (Staphylococcus spp.), Edwards (Streptococcus spp.), and MacConkey (coliform). Following incubation, microbial counts for each pathogen type were manually counted and assigned to one of six categories depending on the microbial counts measured. The results were analysed by logistic regression using SAS [28]. The main analysis was conducted on binary improvement scores for the swabbing outcomes. There were no differences for staphylococcal, streptococcal and coliform bacterial counts between treatments, measured 'before' teat preparation. Treatments containing 'Chlorhexidine' teat foam (OR = 4.46) and 'Wipes' (OR = 4.46) resulted in a significant reduction (P < 0.01) in the staphylococcal count on teats compared to 'Washing and drying' or 'No preparation'. 'Chlorine' teat foam (OR = 3.45) and 'Wipes' (3.45) had the highest probability (P < 0.01) of reducing streptococcal counts compared to 'Washing and drying' or 'No preparation'. There was no statistical difference between any of the disinfectant treatments applied in reducing coliforms. Thus, the use of some disinfectant products for pre-milking teat preparation can have beneficial effects on reducing the levels of staphylococcal and streptococcal pathogens on teat skin

Hawtreyan 'credit deadlock' or Keynesian 'liquidity trap'? Lessons for Japan from the great depression

This paper outlines the ideas of Ralph Hawtrey and Lauchlin Currie on the need for monetised fiscal deficit spending in 1930s USA to combat the deep depression into which the economy had been allowed to sink. In such exceptional circumstances of 'credit deadlock' in which banks were afraid to lend and households and business afraid to borrow, the deadlock could best be broken through the spending of new money into circulation via large fiscal deficits. This complementarity of fiscal and monetary policy was shown to be essential, and as such indicates the potential power of monetary policy - in contrast to the Keynesian "liquidity trap" view that it is powerless This lesson was not learned by the Japanese authorities in their response to the asset price collapse of 1991-92, resulting in a lost decade as ballooning fiscal deficits were neutralised throughout the 1990s by unhelpfully tight monetary policy with the Bank of Japan refusing to monetise the deficits

Backpack-mounted satellite transmitters do not affect reproductive performance in a migratory bustard

Backpack-mounted satellite transmitters (PTTs) are used extensively in the study of avian habitat use and of the movements and demography of medium- to large-bodied species, but can affect individuals’ performance and fitness. Transparent assessment of potential transmitter effects is important for both ethical accountability and confidence in, or adjustment to, life history parameter estimates. We assessed the influence of transmitters on seven reproductive parameters in Asian houbara Chlamydotis macqueenii, comparing 114 nests of 38 females carrying PTTs to 184 nests of untagged birds (non-PTT) over seven breeding seasons (2012‒2018) in Uzbekistan. There was no evidence of any influence of PTTs on: lay date (non-PTT x̅ = 91.7 Julian day ± 12.3 SD; PTT x̅ = 95.1 Julian day ± 15.7 SD); clutch size (non-PTT x̅ = 3.30 ± 0.68 SD; PTT x̅ = 3.25 ± 0.65 SD); mean egg weight at laying (non-PTT x̅ = 66.1g ± 5.4 SD; PTT x̅ = 66.4g ± 5.4 SD); nest success (non-PTT x̅ = 57.08% ± 4.3 SE; PTT x̅ = 58.24% ± 4.5 SE for nests started 2 April); egg hatchability (non-PTT x̅ = 88.3% ± 2.2 SE; PTT x̅ = 88.3% ± 2.6 SE); or chick survival to fledging from broods that had at least one surviving chick (non-PTT x̅ = 63.4% ± 4.2 SE; PTT x̅= 64.4% ± 4.7 SE). High nesting propensity (97.3% year-1 ± 1.9% SE) of tagged birds indicated minimal PTT effect on breeding probability. These findings show harness-mounted transmitters can give unbiased measures of demographic parameters of this species, and are relevant to other large-bodied, cursorial, ground-nesting birds of open habitats, particularly other bustards

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Single pi+ Electroproduction on the Proton in the First and Second Resonance Regions at 0.25GeV^2 < Q^2 < 0.65GeV^2 Using CLAS

The ep -> e'pi^+n reaction was studied in the first and second nucleon resonance regions in the 0.25 GeV^2 < Q^2 < 0.65 GeV^2 range using the CLAS detector at Thomas Jefferson National Accelerator Facility. For the first time the absolute cross sections were measured covering nearly the full angular range in the hadronic center-of-mass frame. The structure functions sigma_TL, sigma_TT and the linear combination sigma_T+epsilon*sigma_L were extracted by fitting the phi-dependence of the measured cross sections, and were compared to the MAID and Sato-Lee models.Comment: Accepted for publication in PR

Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure

π0\pi^0 photoproduction on the proton for photon energies from 0.675 to 2.875 GeV

Differential cross sections for the reaction $\gamma p \to p \pi^0$ have been measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged photon beam with energies from 0.675 to 2.875 GeV. The results reported here possess greater accuracy in the absolute normalization than previous measurements. They disagree with recent CB-ELSA measurements for the process at forward scattering angles. Agreement with the SAID and MAID fits is found below 1 GeV. The present set of cross sections has been incorporated into the SAID database, and exploratory fits have been extended to 3 GeV. Resonance couplings have been extracted and compared to previous determinations.Comment: 18 pages, 48 figure

Exclusive ρ0\rho^0 electroproduction on the proton at CLAS

The $e p\to e^\prime p \rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply inapplicable in this region due to higher-twists contributions, incalculable at present.Comment: 29 pages, 29 figure

First Measurement of Beam-Recoil Observables Cx and Cz in Hyperon Photoproduction

Spin transfer from circularly polarized real photons to recoiling hyperons has been measured for the reactions $\vec\gamma + p \to K^+ + \vec\Lambda$ and $\vec\gamma + p \to K^+ + \vec\Sigma^0$. The data were obtained using the CLAS detector at Jefferson Lab for center-of-mass energies $W$ between 1.6 and 2.53 GeV, and for $-0.85<\cos\theta_{K^+}^{c.m.}< +0.95$. For the $\Lambda$, the polarization transfer coefficient along the photon momentum axis, $C_z$, was found to be near unity for a wide range of energy and kaon production angles. The associated transverse polarization coefficient, $C_x$, is smaller than $C_z$ by a roughly constant difference of unity. Most significantly, the {\it total} $\Lambda$ polarization vector, including the induced polarization $P$, has magnitude consistent with unity at all measured energies and production angles when the beam is fully polarized. For the $\Sigma^0$ this simple phenomenology does not hold. All existing hadrodynamic models are in poor agreement with these results.Comment: 28 pages, 18 figures, Submitted to Physical Review