Trypanosoma congolense: paraoxonase 1 prolongs survival of infected mice

In vitro studies have suggested that a fraction of human high density lipoprotein (HDL), termed trypanosome lysis factor (TLF), can protect against trypanosome infection. We examined the involvement of two proteins located in the TLF fraction, apolipoprotein A-II (apoA-II) and paraoxonase 1 (PON1), against trypanosome infection. To test whether PON1 is involved in trypanosome resistance, we infected human PON1 transgenic mice, PON1 knockout mice, and wild-type mice with Trypanosoma congolense. When challenged with the same dosage of trypanosomes, mice overexpressing PON1 lived significantly longer than wild-type mice, and mice deficient in PON1 lived significantly shorter. In contrast, mice overexpressing another HDL associated protein, apoA-II, had the same survival as wild-type mice. Together, these data suggest that PON1 provides protection against trypanosome infection. In vitro studies using T. brucei brucei indicated that HDL particles containing PON1 and those depleted of PON1 did not differ in their lysis ability, suggesting that protection by PON1 is indirect. Our data are consistent with an in vivo role of HDL protection against trypanosome infection.     

YKE4 (YIL023C) encodes a bidirectional zinc transporter in the endoplasmic reticulum of Saccharomyces cerevisiae

YIL023C encodes a member of the SLC39A, or ZIP, family, which we refer to as yeast KE4 (YKE4) after its mouse ortholog. Yke4p was localized to the endoplasmic reticulum (ER) membrane using Yke4p-specific antiserum. YKE4 is not an essential gene; however, deletion of YKE4 resulted in a sensitivity to calcofluor white and poor growth at 36 degrees C on respiratory substrates containing high zinc. Overexpression of transition metal transporters Zrc1p and Cot1p or the mouse orthologue mKe4 in Deltayke4 suppressed the poor growth at 36 degrees C on respiratory substrates. We found that the role of Yke4p depends on the zinc status of the cells. In a zinc-adequate environment, Yke4p transports zinc into the secretory pathway, and the deletion of YKE4 leads to a zinc-suppressible cell wall defect. In high zinc medium, transport of zinc into the secretory pathway through Yke4p is a way to eliminate zinc from the cytosol, and deletion of YKE4 leads to toxic zinc accumulation in the cytosol. Under low cytosolic zinc conditions, however, Yke4p removes zinc from the secretory pathway, and deletion of YKE4 partially compensates for the loss of Msc2p, an ER zinc importer, and therefore helps to alleviate ER stress. In our model, Yke4p balances zinc levels between the cytosol and the secretory pathway, whereas the previously described Msc2p-Zrg17p ER zinc importer complex functions mainly in zinc-depleted conditions to ensure a ready supply of zinc essential for ER functions, such as phospholipid biosynthesis and unfolded protein response.     

Ramalin, a novel nontoxic antioxidant compound from the Antarctic lichen Ramalina terebrata

Ramalin (γ-glutamyl-N′-(2-hydroxyphenyl)hydrazide), a novel compound, was isolated from the methanol-water extract of the Antarctic lichen Ramalina terebrata by several chromatographic methods. The molecular structure of ramalin was determined by spectroscopic analysis. The experimental data showed that ramalin was five times more potent than commercial butylated hydroxyanisole (BHA) in scavenging 1-diphenyl-2-picryl-hydazil (DPPH) free radicals, 27 times more potent in scavenging 2,2′-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid free radicals (ABTS⁺) than the vitamin E analogue, trolox, and 2.5 times more potent than BHT in reducing Fe³⁺ to Fe²⁺ ions. Similarly, ramalin was 1.2 times more potent than ascorbic acid in scavenging superoxide radicals and 1.25 times more potent than commercial kojic acid in inhibiting tyrosinase enzyme activity, which ultimately leads to whitening of skin cells. Ramalin showed no or very little cytotoxicity in human keratinocyte and fibroblast cells at its antioxidant concentration. Furthermore, ramalin was assessed to determine its antioxidant activity in vivo. One microgram per milliliter ramalin significantly reduced the released nitric oxide (NO) and 0.125 μg/ml ramalin reduced the produced hydrogen peroxide (H₂O₂) in LPS (lipopolysaccharide)-stimulated murine macrophage Raw264.7 cells. Considering all the data together, ramalin can be a strong therapeutic candidate for controlling oxidative stress in cells.     

An electrical biosensor for the detection of circulating tumor cells

In this report, we demonstrate a semi-integrated electrical biosensor for the detection of rare circulating tumor cells (CTCs) in blood. The sample was first enriched through a combination of immunomagnetic isolation and size filtration. The integration of both methods provided a high enrichment performance with a recovery rate above 70%, even for very low numbers of cancer cells present in the original sample (10 spiked MCF7 cells in 0.5 mL of blood). In the same system, the sample was then transferred to a microchip for further magnetic concentration, followed by immunochemical trapping and electronic detection by impedance spectroscopy. Three levels of spiked CTC number (30±2, 124±29, 273±23) in 10 μL of filtered blood sample were distinguished by monitoring the impedance change of the microelectrode array (MEA). The integration of different functions in a single system provided a methodology to process milliliter-sized blood samples at the macroscale and interface with the microdimensions of a highly sensitive electronic detector. The results showed that the whole system was able to detect different levels of spiked cancer cells without the use of time- and cost-intensive fluorescence labeling and image analysis. This has the potential to provide clinicians with a standalone system to monitor changes in CTC numbers throughout therapy conveniently and frequently for efficient cancer treatments.     

Female stickleback prefer shallow males: Sexual selection on nest microhabitat

Sexual selection is most often thought of as acting on organismal traits, such as size or color. However, individuals’ habitat use may also affect mating success. Here, we show that, in threespine stickleback, nest depth can be a target of sexual selection. In postglacial lakes in British Columbia, male threespine stickleback nest in a narrow range of depths. Prior studies revealed heritable variation in males’ preferred nest microhabitat. We surveyed four natural populations, finding that male stickleback with shallower nests were more successful at breeding. Indeed, nest depth was a much stronger predictor of male mating success than more commonly studied targets of sexual selection in stickleback (size, condition, shape, color, infection status). This selection on nest depth means that variance in fitness changed predictably across microhabitats, altering the opportunity for sexual selection to act on other traits. Accordingly, we show that sexual selection on other male traits is strongest where variance in nesting success is highest (at intermediate nest depths in some lakes). We conclude that males’ choice of nesting microhabitat is an especially important target of sexual selection, resulting in fine‐scale spatial variation in sexual selection on other traits.     

Granulosicoccaceae fam. nov., to include Granulosicoccus antarcticus gen. nov., sp. nov., a non-phototrophic, obligately aerobic chemoheterotroph in the order Chromatiales, isolated from Antarctic seawater

A Gram-negative, motile by tuft flagella, obligately aerobic chemoorganoheterotrophic, sphere-form bacterium, designated IMCC3135(T), was isolated from the Antarctic surface seawater of King George Island, West Antarctica. The strain was mesophilic, neutrophilic, and requiring NaCl for growth, but neither halophilic nor halotolerant. The 16S rRNA gene sequence analysis indicated that the strain was most closely related to genera of the order Chromatiales in the class Gammaproteobacteria. The most closely related genera showed less than 90% 16S rRNA gene sequence similarity and included Thioalkalispira (89.9%), Thioalkalivibrio (88.0%-89.5%), Ectothiorhodospira (87.9%-89.3%), Chromatium (88.3%-88.9%), and Lamprocystis (87.7%-88.9%), which represent three different families of the order Chromatiales. Phylogenetic analyses showed that this Antarctic strain represented a distinct phylogenetic lineage in the order Chromatiales and could not be assigned to any of the defined families in the order. Phenotypic characteristics, including primarily non-phototrophic, non-alkaliphilic, non-halophilic, and obligately aerobic chemoheterotrophic properties, differentiated the strain from other related genera. The very low sequence similarities (<90%) and distant relationships between the strain and members of the order suggested that the strain merited classification as a novel genus within a novel family in the order Chromatiales. On the basis of these taxonomic traits, a novel genus and species is proposed, Granulosicoccus antarcticus gen. nov., sp. nov., in a new family Granulosicoccaceae fam. nov. Strain IMCC3135(T) (=KCCM 42676(T)=NBRC 102684(T)) is the type strain of Granulosicoccus antarcticus.     

Novel cancer stem cell marker MVP enhances temozolomide-resistance in glioblastoma

The resistance of highly aggressive glioblastoma multiforme (GBM) to chemotherapy is a major clinical problem resulting in a poor prognosis. GBM contains a rare population of self-renewing cancer stem cells (CSCs) that proliferate, spurring the growth of new tumors, and evade chemotherapy. In cancer, major vault protein (MVP) is thought to contribute to drug resistance. However, the role of MVP as CSCs marker remains unknown and whether MVP could sensitize GBM cells to Temozolomide (TMZ) also is unclear. We found that sensitivity to TMZ was suppressed by significantly increasing the MVP expression in GBM cells with TMZ resistance. Also, MVP was associated with the expression of other multidrug-resistant proteins in tumorsphere of TMZ-resistant GBM cell, and was highly co-expressed with CSC markers in tumorsphere culture. On the other hands, knockdown of MVP resulted in reduced sphere formation and invasive capacity. Moreover, high expression of MVP was associated with tumor malignancy and survival rate in glioblastoma patients. Our study describes that MVP is a potentially novel maker for glioblastoma stem cells and may be useful as a target for preventing TMZ resistance in GBM patients.