SYNTHETIC STUDIES TOWARDS THE SYNTHESIS OF ANATOXIN-A(S)

Three routes toward the total synthesis of the neurotoxin anatoxin-a(s) have been explored. They focus on the assembly of the backbone utilizing both Pd(0)- and Pd(II)-mediated processes. Our current route leads to a late-stage precursor of anatoxin-a(s), hydroxy guanidine 134, in 18 steps and in 8.0% overall yield utilizing an amidoalkylation step in the key cyclization

Role of Protein Kinase Phosphorylation on SERT Oligomerization: A Novel Mechanistic View

The serotonin transporter (SERT) is the primary mechanism for the termination of synaptic signaling. It is of clinical relevance because it is a high-affinity target for therapeutics such as anti-depressants (SSRIs) and drugs of abuse such as cocaine, amphetamine, and 3,4 methylenedioxymethamphetamine (ecstasy). It is also seen as a protein potentially involved in the etiology underlying disorders such as clinical depression, autism, anxiety-related disorders, obsessive compulsive disorder, and anorexia nervosa among others. SERT has also been found to be a target of protein kinases that exert their effects through phosphorylation. For example, activation of protein kinase C (PKC) decreases SERT uptake of serotonin (5-HT) by increasing internalization of SERT from the plasma membrane. Conversely, phosphorylation of SERT by protein kinase G (PKG) appears to increase SERT uptake of 5-HT from the synapse. It has also been thought that oligomerization of SERT is a necessary component of endoplasmic reticulum (ER) exocytosis and plasma membrane expression. However, there has been no common tie between these two very important processes of SERT regulation. In this study, we examined regulation of SERT phosphorylation\u27s effect on SERT oligomerization. Our results indicated that phosphorylation of SERT by kinases that stimulate 5-HT uptake, p38 mitogen-activated protein kinase (MAPK) and PKG decrease SERT oligomerization in HEK-293 cells. We also identified the putative phosphorylation site of SERT for PKG. PKC however showed the opposite effect by increasing SERT oligomerization upon activation with phorbol esters. In this study we also show that phosphorylation is a potential mechanism for regulating the oligomeric state of SERT using site-directed mutagenesis at a putative site in SERT phosphorylated by PKG. Lastly, we show that human mutant polymorphisms found in patients with obsessive compulsive disorder and other serotonin-related disorders, that have been shown to increase 5-HT uptake by SERT, appear to decrease the homo-oligomeric complex of SERT much like PKG and p38 MAPK. Lastly, we show that oligomerization is necessary for correct protein expression and that physiologically relevant concentrations of cocaine appear to increase SER T oligomerization. These results show for the first time that the oligomerization status of SERT can be regulated by protein kinases

Seed produced anti ETEC antibodies for oral passive immunisation of piglets against post weaning diarrhoea

C

Brief for Respondents. Integrity Staffing Solutions, Inc. v. Busk, 135 S.Ct. 513 (2014) (No. 13-433), 2014 WL 3866627

QUESTIONS PRESENTED (1) Does the time an hourly employee spends participating in an employer-mandated anti-theft search constitute work within the meaning of the Fair Labor Standards Act? (2) If such a search occurs at the end of the workday, is the employee’s time nonetheless non-compensable as a postliminary activity under the Portal-to-Portal Act

Performing “culture” : diverse audiences at the International Shaman’s Conference and Tailgan on Ol’khon Island

Cet article examine la session annuelle de la Conférence Chamanique Internationale et du Tailgan sur l’île d’Ol’hon, dans le lac Baïkal, sous l’angle de la prestation “culturelle” qu’elle présentait. Il en découle une question de méthode : les données relatives aux participants aident-elles à comprendre la cérémonie ? L’enquête démographique montre la grande diversité du public ; du fait de la variété des raisons d’assister et des attentes, les impressions retirées de cette session sont très différentes. La cérémonie elle-même reflète cette diversité, que les discours d’ouverture ont pragmatiquement tenté d’encadrer en parlant de “culture locale à valeur globale”. Du fait que “local” et “culture” restent non définis, les Bouriates locaux et les membres de l’association Tengeri peuvent percevoir cette “culture locale” comme une contribution à la revitalisation des pratiques chamaniques bouriates, tout en permettant aux pèlerins New Age de trouver quelque chose d’universel sous une forme bouriate locale.This article explores the presentation and performance of “culture” at the Annual International Shamanic Conference and Tailgan on Olkhon Island, Lake Baikal and poses the methodological question of how survey data about the participants can help us to understand the ceremony. Demographic survey data indicates that there are multiple audiences, who, given widely divergent reasons for attending, are most likely getting very different things out of the ceremony. The ceremony itself reflects this division, with a metapragmatic framing during the opening speeches as “globally valuable local culture”. By leaving “local” and “culture” undefined and unmarked, local Buryats and other Tengeri members can experience it as part of their broader attempt to revive Buryat shamanic practices, while at the same time, enabling New Age pilgrims to find a universal appeal in a local Buryat form

Fabrication of Covalently Crosslinked and Amine-Reactive Microcapsules by Reactive Layer-by-Layer Assembly of Azlactone-Containing Polymer Multilayers on Sacrificial Microparticle templates

We report on the fabrication of covalently crosslinked and amine-reactive hollow microcapsules using \u27reactive\u27 layer-by-layer assembly to deposit thin polymer films on sacrificial microparticle templates. Our approach is based on the alternating deposition of layers of a synthetic polyamine and a polymer containing reactive azlactone functionality. Multilayered films composed of branched poly(ethylene imine) (BPEI) and poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) were fabricated layer-by-layer on the surfaces of calcium carbonate and glass microparticle templates. After fabrication, these films contained residual azlactone functionality that was accessible for reaction with amine-containing molecules. Dissolution of the calcium carbonate or glass cores using aqueous ethylenediaminetetraacetic acid (EDTA) or hydrofluoric acid (HF), respectively, led to the formation of hollow polymer microcapsules. These microcapsules were robust enough to encapsulate and retain a model macromolecule (FITC-dextran) and were stable for at least 22 hours in high ionic strength environments, in low and high pH solutions, and in several common organic solvents. Significant differences in the behaviors of capsules fabricated on CaCO3 and glass cores were observed and characterized using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS). Whereas capsules fabricated on CaCO3 templates collapsed upon drying, capsules fabricated on glass templates remained rigid and spherical. Characterization using EDS suggested that this latter behavior results, at least in part, from the presence of insoluble metal fluoride salts that are trapped or precipitated on or within the walls of capsules after etching the glass cores using HF. Our results demonstrate that the assembly of BPEI/PVDMA films on sacrificial templates can be used to fabricate reactive microcapsules of potential use in a wide range of fields, including catalysis, drug and gene delivery, imaging, and biomedical research

Passive mucosal immunisation with novel simplified IgA antibodies produced in seeds prevents enterotoxigenic Escherichia coli (ETEC) infection in weaned piglets

C