An Image Processing Algorithm for Facile and Reproducible Quantification of Vomocytosis.

Vomocytosis is a process that occurs when internalized fungal pathogens escape from phagocytes without compromising the viability of the pathogen and the host cell. Manual quantification of time-lapse microscopy videos is currently used as the standard to study pathogen behavior and vomocytosis incidence. However, human-driven quantification of vomocytosis (and the closely related phenomenon, exocytosis) is incredibly burdensome, especially when a large volume of cells and interactions needs to be analyzed.

Vomocytosis of Cryptococcus neoformans cells from murine, bone marrow-derived dendritic cells.

Cryptococcus neoformans (CN) cells survive within the acidic phagolysosome of macrophages (MΦ) for extended times, then escape without impacting the viability of the host cell via a phenomenon that has been coined 'vomocytosis'. Through this mechanism, CN disseminate throughout the body, sometimes resulting in a potentially fatal condition-Cryptococcal Meningitis (CM). Justifiably, vomocytosis studies have focused primarily on MΦ, as alveolar MΦ within the lung act as first responders that ultimately expel this fungal pathogen.

Autonomous Internal Reflux of Magnetic Nanoparticle Chains in a Flow Channel for Efficient Detection of Waterborne Bacteria.

Herein, we developed a novel method for the efficient capture of waterborne bacteria by creating an autonomous internal reflux of the magnetic nanoparticle chains (MNCs) inside a flow channel. A glass tube containing positively charged polyethyleneimine-coated MNCs (PEI-MNCs) was placed at the center of a Halbach ring, generating a strong and uniform magnetic field inside the ring. When a bacteria-spiked solution was injected into the tube, the target bacteria bound to the PEI-MNCs via an electrostatic interaction remained in the tube, whereas the unbound bacteria left the tube.

Recent advances in magnetic nanoparticle-based microfluidic devices for the pretreatment of pathogenic bacteria.

Rapid and sensitive detection of pathogenic bacteria in various samples, including food and drinking water, is important to prevent bacterial diseases. Most bacterial solutions contain only a small number of bacteria in complex matrices with impurities; hence, pretreatment is necessary to separate and concentrate target bacteria before sensing. Among various pretreatment methods, iron oxide magnetic nanoparticle (MNP)-based pretreatment has drawn attention owing to the unique properties of MNP, such as high magnetic susceptibility, superparamagnetism, and biocompatibility.

Zwitterion-Coated Colloidal Magnetic Nanoparticle Clusters for Reduced Nonspecific Adsorption of Biomolecules.

This paper demonstrates fabrication of silica-shell-coated magnetic nanoparticle clusters (SMNCs) and subsequent surface engineering of SMNCs to produce surface-modified SMNCs that have zwitterionic and primary amine ligands (SMNC-ZW/Am). SMNC-ZW/Am was passivated by zwitterionic ligands for improved colloidal stability and reduced nonspecific adsorption and by primary amine ligands for facilitated conjugation with biomolecules. Hydrodynamic (HD) size and zeta potential of SMNC-ZW/Am could be flexibly tuned by controlling the relative amounts of zwitterionic and primary amine ligands.

Lactate Exposure Promotes Immunosuppressive Phenotypes in Innate Immune Cells.

Introduction: Lactate secreted by tumors is not just a byproduct, but rather an active modulator of immune cells. There are few studies aimed at investigating the true effect of lactate, which is normally confounded by pH. Such a knowledge gap needs to be addressed.

Baleen-Mimicking Virtual Filters for Rapid Detection of Pathogenic Bacteria in Water Using Magnetic Nanoparticle Chains and a Halbach Ring.

We have developed a virtual filter that quickly and efficiently captures and detects pathogenic bacteria in large amounts of water. The virtual filter comprised magnetic nanoparticle chains (MNCs) obtained by cross-linking alginate-coated magnetic nanoparticles (MNPs). When the MNC solution in a disposable plastic tube was exposed to an external magnetic field, the MNCs were aligned along the magnetic field lines, forming a filter similar to a whale's baleen filtering system.

Asymmetric Bisvinylogous Aldolation of Aldehydes via 2-Oxonia-Cope Rearrangement Enabling Total Stereochemical Control.

Highly stereoselective 2-oxonia-Cope rearrangement reactions between newly designed bisvinylogous aldolation synthons and aldehydes, which can provide ε-hydroxy-α,β,γ,δ-unsaturated esters with excellent enantioselectivities, as well as with unprecedented E- and Z-selectivities without regioselectivity issues, are described.

Rationally Designed Chiral Synthons Enabling Asymmetric Z- and E-Selective Vinylogous Aldol Reactions of Aldehydes.

In a conceptually different approach, highly stereoselective 2-oxonia-Cope rearrangement reactions between rationally designed nonracemic vinylogous aldolation synthons and aldehydes are described to provide δ-hydroxy-α,β-unsaturated esters with excellent enantioselectivities and, for the first time, unprecedented Z- and E-selectivities without the regioselectivity issue.

Highly Stereoselective 2-Oxonia-Cope Rearrangement: A Platform Enabling At-Will Control of Regio-, Enantio-, and Diastereoselectivity in the Vinylogous Aldol Reactions of Aldehydes.

A distinctly different approach for the vinylogous aldolation of aldehydes is described, which exploits 2-oxonia-Cope rearrangement reactions between two readily available partners, a set of rationally designed chiral homoallylic alcohol synthons and aldehydes, under simple conditions. In these processes, chirality transfer from the former to the latter is nearly perfect, giving rise to excellent enantio- and diastereoselectivity without the regioselectivity issue associated with traditional vinylogous aldol reactions.

Enantioenriched bifunctional crotylsilanes for the asymmetric synthesis of orthogonally protected 2-methyl-1,3-diols.

Enantiomerically pure α-substituted crotylsilane reagents I and ent-I undergo asymmetric aldehyde crotylation followed by Ir(I)-catalyzed diastereoselective allylic etherification to give a variety of orthogonally protected 2-methyl-1,3-diols at the synthetically useful level of yields and stereoselectivity. The reagents are air-stable and bifunctional so that they can be used in these reactions sequentially without recourse to functional group adjustments.

Air-stable bifunctional allylation reagents for the asymmetric synthesis of differentiated syn- and anti-1,3-diols.

Turning the diols: Enantiomerically pure bifunctional reagents I and ent-I undergo asymmetric aldehyde allylation followed by Ir(I)-catalyzed enantioselective decarboxylative allylic etherification to give differentiated syn- and anti-1,3-diols with complete control of the absolute and relative stereochemistry (see scheme; PMP = para-methoxyphenyl, dbcot = dibenzo[a,e]cyclooctatetraene, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene).

Concise asymmetric synthesis of orthogonally protected syn- and anti-1,3-aminoalcohols.

Novel chiral binfunctional reagents V and ent-V undergo asymmetric aldehyde allylation followed by Ir(I)-catalyzed enantioselective allylic amidation to give orthogonally protected syn- and anti-1,3-aminoalcohols with complete control of absolute and relative stereochemistry. The Mitsunobu reaction of the initial homoallylic alcohol products followed by Ir(I)-catalyzed enantioselective allylic amidation provides orthogonally protected syn- and anti-1,3-diamine derivatives in high yields and with excellent stereoselectivities.

Ir(I)-catalyzed enantioselective decarboxylative allylic etherification: a general method for the asymmetric synthesis of aryl allyl ethers.

Ir(I)-catalyzed enantioselective decarboxylative allylic etherification of aryl allyl carbonates provides aryl allyl ethers. Key to the generality and high stereoselection of the reaction is the use of the intramolecular decarboxylative allylation process and [Ir(dbcot)Cl](2) as an Ir(I) source. Ir(I)-catalyzed diastereoselective decarboxylative allylic etherification, combined with asymmetric aldehyde crotylation and cross metathesis, can furnish monoprotected 2-methyl-1,3-diols (starting from simple aldehydes) with high diastereoselectivities.

Stereoselective Synthesis of trans-Olefins by the Copper-Mediated S(N)2' Reaction of Vinyl Oxazines with Grignard Reagents. Asymmetric Synthesis of D-threo-Sphingosines.

The S(N)2' reaction of 6-vinyl-5,6-dihydro-4H-[1,3]oxazines with Grignard reagents in the presence of CuCN was studied, and high trans selectivity for the formation of double bond was observed with a variety of RMgX. The S(N)2' reaction, coupled with regioselective asymmetric aminohydroxylation reaction, provided a highly efficient route for the asymmetric synthesis of D-threo-N-acetylsphingosine.

Asymmetric Synthesis of (+)-Iso-6-Cassine via Stereoselective Intramolecular Amidomercuration.

The first asymmetric synthesis of (+)-iso-6-cassine is described. Lipase-catalyzed resolution, enantioselective Overman rearrangement, and diastereoselective intramolecular amidomercuration were used for the installation of the three stereocenters in (+)-iso-6-cassine, and cross-metathesis was employed for the attachment of the side-chain.

Iridium(I)-catalyzed stereospecific decarboxylative allylic amidation of chiral branched benzyl allyl imidodicarboxylates.

Ir(I)-catalyzed decarboxylative allylic amidation of chiral branched benzyl allyl imidodicarboxylates has been shown to proceed with complete retention of enantiomeric purity and configuration. The transformation is stereospecific and appears to be quite general, accommodating a wide range of R groups.

Iridium(I)-Catalyzed Regio- and Enantioselective Allylic Amidation.

Ir(I)-catalyzed intermolecular allylic amidation of ethyl allylic carbonates with soft nitrogen nucleophiles under completely "salt-free" conditions is described. A combination of [Ir(COD)Cl](2), a chiral phosphoramidite ligand L*, and DBU as a base in THF effects the reaction. The reaction appears to be quite general, accommodating a wide variety of R-groups and soft nitrogen nucleophiles, and proceeds with excellent regio- and enantioselectivities to afford the branched N-protected allylic amines.

Development of more potent 4-dimethylaminopyridine analogues.

[reaction: see text] The syntheses of bicyclic diaminopyridines 3 and 4 and tricyclic triaminopyridines 5 and 6, two novel series of nucleophilic catalysts, are described. Arguments are made for predicting the superiority of these catalysts over DMAP and even 2, the best esterification catalyst reported to date. The efficiencies of DMAP, PPY, and 2-6 in catalyzing the esterification of tertiary alcohols were compared.

Tandem overman rearrangement and intramolecular amidomercuration reactions. stereocontrolled synthesis of cis- and trans-2,6-dialkylpiperidines.

[reaction: see text] Hg(II)-mediated tandem Overman rearrangement and intramolecular amidomercuration reactions were proven to provide a convenient tool for the stereoselective synthesis of cis- and trans-2,6-disubstituted piperidines. Thus, upon treatment with Hg(OTFA)(2) in THF, the trichloroacetimidate 1 directly transformed into the 2,6-dialkyl piperidine 2 with almost exclusive trans selectivity. The amiodomercuration reaction of the carbamate 7 by Hg(OTFA)(2) in nitromethane showed an excellent cis selectivity.

O-Alkyl Hydroxamates as Metaphors of Enzyme-Bound Enolate Intermediates in Hydroxy Acid Dehydrogenases. Inhibitors of Isopropylmalate Dehydrogenase, Isocitrate Dehydrogenase, and Tartrate Dehydrogenase(1).

The inhibition of Thermus thermophilus isopropylmalate dehydrogenase by O-methyl oxalohydroxamate was studied for comparison to earlier results of Schloss with the Salmonella enzyme. It is a fairly potent (1.2 &mgr;M), slow-binding, uncompetitive inhibitor against isopropylmalate and is far superior to an oxamide (25 mM K(i) competitive) that is isosteric with the ketoisocaproate product of the enzyme.