Glycoproteins: their structure, biosynthesis and possible clinical implications

Glycoproteins carrying asparagine-linked N-glycosyl oligosaccharides have many diverse biological functions. The role of the carbohydrate in these functions is often obscure. However, there is evidence that carbohydrate is involved in stabilization of glycoproteins during passage from the rough endoplasmic reticulum to the cell surface, and in recognition phenomena such as receptor-mediated endocytosis, routing of lysosomal hydrolases to the lysosomes, and the spread of cancer cells to secondary sites. The cell surface carbohydrate of some transformed cell lines tends to be more highly branched than that of the non-transformed controls. The control of branching during synthesis of N-glycosyl oligosaccharides resides in the N-acetylglucosaminyltransferases (GlcNAc-transferases) which initiate these branches. There must be at least seven such GlcNAc-transferases to account for the diversity of structures that have been observed. Our laboratory has developed assays for four of these enzymes. Substrate specificity studies on these enzymes have shed light on some of the control mechanisms involved in the synthesis of highly branched structures. Alterations in these control mechanisms may be important in the pathogenesis of cancer and other disease.     

Recent progress of solution-processed Cu nanowires transparent electrodes and their applications

Research on next-generation transparent electrode (TE) materials to replace expensive and fragile indium tin oxide (ITO) is crucial for future electronics. Copper nanowires (Cu NWs) are considered as one of the most promising alternatives due to their excellent electrical properties and low-cost processing. This review summarizes the recent progress on the synthesis methods of long Cu NWs, and the fabrication techniques and protection measures for Cu NW TEs. Applications of Cu NW TEs in electronics, such as solar cells, touch screens, and light emitting diodes (LEDs), are discussed.

This review summarizes the recent progress on the synthesis methods of long Cu nanowires, fabrication techniques, protection measures and applications for Cu nanowire transparent electrodes.     

Genome-based analysis of the type II PKS biosynthesis pathway of xanthones in Streptomyces caelestis and their antifungal activity

The ethyl acetate extract from the liquid fermentation of S. caelestis Aw99c exhibited high and broad antifungal activities against plant pathogenic fungi. Bioassay guide fractionation led to the discovery of two xanthones, citreamicin ε and θ. The draft genome sequence of S. caelestis Aw99c was analyzed by a similarity-based approach to elucidate the pathway for the citreamicins. A 48 kb citreamicin (cit) gene cluster with 51 open reading frames encoding type II polyketide synthases and unique polyketide tailoring enzymes was proposed based on the genome analysis and the chemical structure derivation. In vitro antifungal assay showed that citreamicin ε exhibited significant growth inhibition against the plant pathogenic fungi with MIC values ranging from 1.56 to 12.5 μM. The cellular structural change of M. grisea treated with citreamicin ε was detected by SEM and the result showed that citreamicin ε caused disruptive surface of the mycelia.

The ethyl acetate extract from the liquid fermentation of S. caelestis Aw99c exhibited high and broad antifungal activities against plant pathogenic fungi.     

Killing of intracellular Leishmania donovani by human mononuclear phagocytes. Evidence for oxygen-dependent and -independent leishmanicidal activity.

Human peripheral blood monocytes were cultivated for 1-30 d before assay for H2O2 release or challenge with Leishmania donovani promastigotes (LDP) or amastigotes (LDA). 1-d cells readily generated H2O2 in response to both phorbol myristate acetate triggering (1,013 +/- 58 nmol/mg protein . 90 min) and LDP ingestion, and killed 50% of LDP within 6 h, and 90% by 24 h. In contrast, the same cells released little H2O2 during LDA ingestion, killed no LDA at 6 h and less than 30% by 24 h, and supported intracellular LDA replication. Monocyte-derived macrophages (cells first cultivated for greater than or equal to 7 d) generated less than 125 nmol H2O2/mg . 90 min after phorbol myristate acetate triggering, killed neither LDP nor LDA, and permitted both forms to replicate. The addition of mitogen- or antigen-stimulated lymphokines, however, prevented the decline in monocyte oxidative capacity, enhanced macrophage H2O2 release by more than sixfold, and, in parallel, induced 1-d monocytes to kill LDA and cultivated macrophages to display both promastigocidal and amastigocidal activity. In comparison to 1-d monocytes and lymphokine-activated macrophages from normal donors, the same cells from patients with chronic granulomatous disease (CGD) or normal cells whose oxidative activity had been impaired by catalase pretreatment or glucose deprivation exerted considerably less or no antileishmanial activity during the early (6-24 h) postphagocytic period. By 48 h after infection, however, 1-d CGD monocytes and oxidatively impaired normal cells killed 40 and greater than 80% of LDP, respectively. Although a longer period of lymphokine stimulation was required and the resulting antileishmanial effects were not as rapid as with normal cells, activated CGD monocytes and macrophages also eventually achieved promastigocidal and amastigostatic activity. These results indicate that human mononuclear phagocytes utilize both oxygen-dependent and -independent mechanisms to achieve activity against ingested Leishmania, and also demonstrate (a) the differential susceptibilities of the two forms of L. donovani to intracellular killing, (b) the key role of oxygen intermediates in effective mononuclear phagocyte antimicrobial activity, (c) the capacity of lymphocyte products to enhance oxygen-dependent as well as -independent pathways, and (d) the vulnerability of the monocyte-derived macrophage to Leishmania infection in the absence of lymphokine stimulation.     

The cryptophycins: their synthesis and anticancer activity

The cryptophycins are a unique family of 16-membered macrolide antimitotic agents isolated from the cyanobacteria Nostoc sp. Their molecular target is tubulin protein wherein they are the most potent known stabilizers of microtubule dynamics and depolymerize microtubules at higher concentrations. They also deactivate the Bcl2 protein and produce apoptotic response much more quickly and at considerably lower concentrations than clinically utilized compounds. The presence of several amide and ester linkages within the cryptophycin core provides access to very convergent total synthetic approaches. Likewise, the modularity of the structure renders their synthesis amenable to structure-activity studies in several regions of the molecule. The in vivo hydrolytic instability of the C5 ester was a key obstacle to the successful identification of a clinical candidate. This problem was ameliorated by increased substitution at C6 as in the presence of gem-dimethyl substitution in the clinical candidate, cryptophycin-52.     

Calcium cycling proteins and their association with heart failure

Heart failure (HF) has reached epidemic proportions in the United States and is one of the most important challenges to public health. Severe congestive HF is associated with substantial morbidity and mortality. HF afflicts approximately 5 million patients and contributes to 3 million hospitalizations and 300,000 deaths yearly. Late-stage HF has a poor prognosis, and therapeutic options are limited. Defective excitation–contraction (EC) coupling in HF may result from altered density or function of proteins relevant for Ca2+ homeostasis.     

Pt and RhPt dendritic nanowires and their potential application as anodic catalysts for fuel cells

Fuel cells have a number of benefits over conventional combustion-based technologies and can be used in a range of important applications, including transportation, as well as stationary, portable and emergency backup power systems. One of the major challenges in this field, however lies in controlling catalyst design which is critical for developing efficient and cost-effective fuel cell technology. Herein, for the first time, we report a facile controlled synthesis of Pt and RhPt dendritic nanowires using ultrathin AuAg nanowires as sacrificial templates. These dendritic nanowires exhibit remarkable catalytic performance in the elecrochemical oxidation of methanol and formic acid. In particular, the RhPt dendritic nanostructures show very high resistance to catalyst poisoning in methanol oxidation. This research demonstrates the advantages of using bimetallic dendritic nanostructures and we believe that these materials and electrocatalytic studies are important for further advancement of fuel cell research and technology.

Fuel cells have a number of benefits over conventional combustion-based technologies and can be used in a range of important applications, including transportation, as well as stationary, portable and emergency backup power systems.     

Antimycobacterial activity of cerulenin and its effects on lipid biosynthesis

Cerulenin is a potent inhibitor of fatty acid synthase (FAS) in a variety of prokaryotic and eukaryotic cells. Using a standardized mycobacterial susceptibility test, we have observed that cerulenin inhibits the growth of several species of mycobacteria, including tuberculous species such as Mycobacterium tuberculosis (H37Rv and clinical isolates) and Mycobacterium bovis BCG (hereafter called BCG), as well as several non-tuberculous species: Mycobacterium smegmatis, the Mycobacterium avium-intracellulare complex (MAC), Mycobacterium kansasii and others. All species and strains tested, including multi-drug resistant isolates of M. tuberculosis, were susceptible to cerulenin with MICs ranging from 1.5 to 12.5 mg/L. Two-dimensional thin-layer chromatography revealed different inhibition patterns of lipid synthesis between tuberculous and non-tuberculous mycobacteria. Cerulenin treatment resulted in a relative increase in phospholipids and mycolic acids in MAC and M. smegmatis, whereas in cerulenin-treated BCG, phospholipids and mycolic acids diminished relative to controls. In addition, long-chain extractable lipids (intermediate in polarity), triglycerides and glycopeptidolipids decreased with cerulenin treatment in all three species of mycobacteria tested. Qualitative changes in several of these lipid classes indicate inhibition in the synthesis of intermediate and long-chain fatty acids. Our results suggest that cerulenin's primary effect may be inhibition of intermediate and long-chain lipid synthesis, with little effect on the synthesis of other lipid classes. In addition, the BCG-specific reduction in phospholipids and mycolic acids suggests the presence of a unique cerulenin-sensitive FAS system in tuberculous mycobacteria. Since pathogenic mycobacteria produce novel long-chain fatty acids, inhibition of fatty acid synthesis offers a potential target for the development of antimycobacterial drugs.     

Nitro derivatives: considerations on their antiplatelet activity

The antischemic effect of nitrates is known and well accepted since more than 100 years, but recently many and interesting studies about antiaggregant property of such drugs have been reported. This action would be lied to increased synthesis of GMPc. The antiaggregant property pf nitrates may be leave open the problem to include the nitrates between the drugs able to influence the prognosis of myocardial infarction both in acute and chronic phase, such as betablockers, ASA and thrombolytics.     

Phonon transport and thermal conductivity of diamond superlattice nanowires: a comparative study with SiGe superlattice nanowires

Due to the coupling of a superlattice''s longitudinal periodicity to a nanowire''s radial confinement, the phonon transport properties of superlattice nanowires (SLNWs) are expected to be radically different from those of pristine nanowires. In this work, we present the comparative investigation of phonon transport and thermal conductivity between diamond SLNWs and SiGe SLNWs by using molecular dynamics simulations. In the case of period length ∼ 25 Å, the thermal conductivities of diamond SLNWs and SiGe SLNWs both increase linearly with increasing the period number, which implies the wave-like coherent phonons dominate the heat transport of SLNWs. In the case of period length ∼ 103 Å, the thermal conductivity of SiGe SLNWs is length-independent with increasing the period number, indicating that the particle-like incoherent phonons in SiGe SLNWs control the heat transport, because the phonon–phonon scattering causes phonons to not retain their phases and the coherence is destroyed before the reflection at interfaces. However in diamond SLNWs the coherent phonons still dominate heat conduction and the thermal conductivity is length-dependent, because the mean free path of phonon–phonon scattering in diamond SLNWs is much longer. The spatial distribution of phonon localized modes further supports these opinions. These results are helpful not only to understand the coherent and incoherent phonon transport, but also to modulate the thermal conductivity of SLNWs.

We present the comparative investigation of phonon transport and thermal conductivity between diamond SLNWs and SiGe SLNWs by molecular dynamics simulations.     

Recent advances in photochemical and electrochemically induced thiocyanation: a greener approach for SCN-containing compound formation

Techniques utilizing photo- and electrochemically induced reactions have been developed to accelerate organic processes. These techniques use light or electrical energy (electron transfer) as a direct energy source without using an initiator or reagent. Thiocyanates are found in biologically active and pharmacological compounds and can be converted into various functional groups. It is one of the most prominent organic scaffolds. Significant development in photo- and electro-chemically induced thiocyanation procedures has been made in recent years for the conception of carbon-sulfur bonds and synthesis of pharmaceutically important molecules. This review discusses different photo- and electro-chemically driven thiocyanation C(sp³)–SCN, C(sp²)–SCN, and C(sp)–SCN bond conception processes that may be useful to green organothiocyanate synthesis. We focus on the synthetic and mechanistic characteristics of organic photo- and electrochemically accelerated C–SCN bond formation thiocyanation reactions to highlight major advances in this novel green and sustainable research field.

Techniques utilizing photo- and electrochemically induced reactions have been developed to accelerate organic processes.     

Facile synthesis of wavy carbon nanowires via activation-enabled reconstruction and their applications towards nanoparticles separation and catalysis

We report a facile synthesis of wavy carbon nanowires (WCNWs) derived from polyurethane via KOH activation. The success of this synthesis relies on a carefully designed activation procedure, which involved one pre-activation stage to form suitable precursor and one high-temperature activation stage to allow directional carbon reconstruction. In particular, PU was initially mixed with KOH and thermally treated sequentially at 400 °C and 800 °C for 1 hour, respectively. The resultant products exhibit high purity in the shape of wavy wire, together with a uniform diameter of 51 ± 5.2 nm and the length in the range of 2–8 μm. Systematic studies have been conducted to investigate the effect of reaction parameters in two activation stages on the morphology and structure of final products. It is worth noting that the as-prepared WCNWs could find promising use in the field of both nanoparticle separation and catalysis. For example, they exhibit outstanding separation abilities towards Au nanospheres with different sizes and enhanced catalytic performance when serving as the catalyst support for Pd towards ethanol oxidation reaction. Particularly, the peak current density of Pd/WCNWs catalysts can reach 2126 mA mg_Pd⁻¹ and the value of its electrochemical active surface area is 60.5 m² g_Pd⁻¹.

This work addresses a niche and facile synthesis of wavy carbon nanowires and their applications in nanoparticles separation and catalysis.     

Calcium carbonate as a phosphate binder: is there a need to adjust peritoneal dialysate calcium concentrations for patients using CaCO3?

The widespread use of calcium carbonate as a phosphate binder is limited by its tendency to develop hypercalcemia in some patients using effective dosages needed to control hyperphosphatemia. Most common continuous ambulatory peritoneal dialysis (CAPD) regimens using dialysis solutions containing 3.5 mEq/L of calcium result in net absorption of calcium from the dialysis solution and, hence limit the amount of oral calcium that can be administered. Peritoneal dialysis solutions with reduced calcium levels are needed for effective use of CaCO3 to control hyperphosphatemia in some dialysis patients.