Effect of preoperative thoracic duct drainage on canine kidney transplantation

Chronic drainage of the thoracic duct to the esophagus was developed in dogs, and its efficacy in immunomodulation was tested using kidney transplantation. Compared to 9.7 days in the control, the mean animal survival was prolonged to 9.9 days, 17.8 days, and 18.5 days when TDD was applied preoperatively for 3 weeks, 6 weeks, and 9 weeks, respectively. Prolongation was significant after 6 weeks. Patency of the fistula was 93.5, 80.4, and 76.1% at respective weeks. Number of peripheral T-lymphocytes determined by a new monoclonal antibody diminished after 3 weeks. All animals were in normal health, requiring no special care for fluid, electrolyte, or protein replacement

A Boiling‐Water‐Stable, Tunable White‐Emitting Metal–Organic Framework from Soft‐Imprint Synthesis

A new avenue for making porous frameworks has been developed by borrowing an idea from molecularly imprinted polymers (MIPs). In lieu of the small molecules commonly used as templates in MIPs, soft metal components, such as CuI, are used to orient the molecular linker and to leverage the formation of the network. Specifically, a linear dicarboxylate linker with thioether side groups reacted simultaneously with Ln3+ ions and CuI, leading to a bimetallic net featuring strong, chemically hard Eu3+–carboxylate links, as well as soft, thioether‐bound Cu2I2 clusters. The CuI block imparts water stability to the host; with the tunable luminescence from the lanthanide ions, this creates the first white‐emitting MOF that is stable in boiling water. The Cu2I2 block also readily reacts with H2S, and enables sensitive colorimetric detection while the host net remains intact.White light/white heat: A porous metal–organic framework, inspired by conceptually crosscutting the molecular imprint of polymers and the template of zeolites, emits white light in boiling water. The MOF incorporates an effective hard‐and‐soft divide, in which the EuIII–carboxylate framework holds up the primary grid, whereas the imbedded soft CuI block, like a template, can be dislodged (e.g., by reacting with H2S) from the surrounding sulfur donors while the host net remains intact.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/137455/1/chem201504941-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/137455/2/chem201504941.pd

Molecularly imprinted polymer based on MWCNTs-QDs as fluorescent biomimetic sensor for specific recognition of target protein

A novel molecularly imprinted optosensing material based on multi-walled carbon nanotube-quantum dots (MWCNT-QDs) has been designed and synthesized for its high selectivity, sensitivity and specificity in the recognition of a target protein bovine serum albumin (BSA). Molecularly imprinted polymer coated MWCNT-QDs using BSA as the template (BMIP-coated MWCNT-QDs) exhibits a fast mass-transfer speed with a response time of 25 min. It is found that the BSA as a target protein can significantly quench the luminescence of BMIP-coated MWCNT-QDs in a concentration-dependent manner that is best described by a Stem-Volmer equation. The K-SV for BSA is much higher than bovine hemoglobin and lysozyme, implying a highly selective recognition of the BMIP-coated MWCNT-QDs to BSA. Under optimal conditions, the relative fluorescence intensity of BMIP-coated MWCNT-QDs decreases linearly with the increasing target protein BSA in the concentration range of 5.0 x 10(-7)-35.0 x 10(-7) M with a detection limit of 80 nM

Emergence of qualia from brain activity or from an interaction of proto-consciousness with the brain: which one is the weirder? Available evidence and a research agenda

This contribution to the science of consciousness aims at comparing how two different theories can explain the emergence of different qualia experiences, meta-awareness, meta-cognition, the placebo effect, out-of-body experiences, cognitive therapy and meditation-induced brain changes, etc. The first theory postulates that qualia experiences derive from specific neural patterns, the second one, that qualia experiences derive from the interaction of a proto-consciousness with the brain\u2019s neural activity. From this comparison it will be possible to judge which one seems to better explain the different qualia experiences and to offer a more promising research agenda

Calcium and Vitamin D increase mRNA levels for the growth control hIK1 channel in human epidermal keratinocytes but functional channels are not observed

BACKGROUND: Intermediate-conductance, calcium-activated potassium channels (IKs) modulate proliferation and differentiation in mesodermal cells by enhancing calcium influx, and they contribute to the physiology of fluid movement in certain epithelia. Previous reports suggest that IK channels stimulate proliferative growth in a keratinocyte cell line; however, because these channels indirectly promote calcium influx, a critically unique component of the keratinocyte differentiation program, an alternative hypothesis is that they would be anti-proliferative and pro-differentiating. This study addresses these hypotheses. METHODS: Real-time PCR, patch clamp electrophysiology, and proliferation assays were used to determine if human IK1 (hIK1) expression and function are correlated with either proliferation or differentiation in cultured human skin epidermal keratinocytes, and skin biopsies grown in explant culture. RESULTS: hIK1 mRNA expression in human keratinocytes and skin was increased in response to anti-proliferative/pro-differentiating stimuli (elevated calcium and Vitamin D). Correspondingly, the hIK1 agonist 1-EBIO inhibited keratinocyte proliferation suggesting that the channel could be anti-proliferative and pro-differentiating. However, this proliferative inhibition by 1-EBIO was not reversed by a panel of hIK1 blockers, calling into question the mechanism of 1-EBIO action. Subsequent patch clamp electrophysiological analysis failed to detect hIK1 channel currents in keratinocytes, even those expressing substantial hIK1 mRNA in response to calcium and Vitamin D induced differentiation. Identical electrophysiological recording conditions were then used to observe robust IK1 currents in fibroblasts which express IK1 mRNA levels comparable to those of keratinocytes. Thus, the absence of observable hIK1 currents in keratinocytes was not a function of the electrophysiological techniques. CONCLUSION: Human keratinocyte differentiation is stimulated by calcium mobilization and influx, and differentiation stimuli coordinately upregulate mRNA levels of the calcium-activated hIK1 channel. This upregulation is paradoxical in that functional hIK1 channels are not observed in cultured keratinocytes. It appears, therefore, that hIK1 does not contribute to the functional electrophysiology of primary human keratinocytes, nor intact human skin. Further, the results indicate caution is required when interpreting experiments utilizing pharmacological hIK1 modulators in human keratinocytes

Molecularly Imprinted Polymers: Present and Future Prospective

Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented

Structural and Functional Diversity of Acidic Scorpion Potassium Channel Toxins

Background: Although the basic scorpion K + channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K + channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly. Principal Findings: Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new a-KTx subfamilies (a-KTx28, a-KTx29, and a-KTx30), and two are new members of the known k-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the a-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized a-helix-loop-b-sheet (CS-a/b) fold motif that has no apparent a-helixs and b-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a Kd of 11.69 mM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized a-helix-loop-helix (CS-a/a) fold scaffold motif

Phosphorylation of Nicastrin by SGK1 Leads to Its Degradation through Lysosomal and Proteasomal Pathways

The gamma-secretase complex is involved in the intramembranous proteolysis of a variety of substrates, including the amyloid precursor protein and the Notch receptor. Nicastrin (NCT) is an essential component of the gamma-secretase complex and functions as a receptor for gamma-secretase substrates. In this study, we determined that serum- and glucocorticoid-induced protein kinase 1 (SGK1) markedly reduced the protein stability of NCT. The SGK1 kinase activity was decisive for NCT degradation and endogenous SGK1 inhibited gamma-secretase activity. SGK1 downregulates NCT protein levels via proteasomal and lysosomal pathways. Furthermore, SGK1 directly bound to and phosphorylated NCT on Ser437, thereby promoting protein degradation. Collectively, our findings indicate that SGK1 is a gamma-secretase regulator presumably effective through phosphorylation and degradation of NCT