Bioconversion of lignocellulose in solid substrate fermentation

Abstract In this review the state of the art of lignocellulose bioconversion by solid substrate fermentation (SSF) is presented. The most important lignocellulolytic fungi and their properties are described, and their application in novel solid state bioreactors with on-line process control is discussed. The most important bioconversion products, biofuels, enzymes, animal feeds, biofertilizers, biopesticides, biopromoters, secondary metabolites, and the economy of their production by SSF is discussed. The use of SSF in the pulp and paper industry and in integrated crop management is illustrated

ABCC6 is a basolateral plasma membrane protein

RATIONALE:: ABCC6 plays a crucial role in ectopic calcification; mutations of the gene cause pseudoxanthoma elasticum and general arterial calcification of infancy. To elucidate the role of ABCC6 in cellular physiology and disease, it is crucial to establish the exact subcellular localization of the native ABCC6 protein. OBJECTIVE:: In a recent article in Circulation Research, ABCC6 was reported to localize to the mitochondria-associated membrane and not the plasma membrane. As the suggested mitochondrial localization is inconsistent with published data and the presumed role of ABCC6, we performed experiments to determine the cellular localization of ABCC6 in its physiological environment. METHODS AND RESULTS:: We performed immunofluorescent labeling of frozen mouse and human liver sections, as well as primary hepatocytes. We used several different antibodies recognizing human and mouse ABCC6. Our results unequivocally show that ABCC6 is in the basolateral membrane of hepatocytes and is not associated with the mitochondria, mitochondria-associated membrane, or the endoplasmic reticulum. CONCLUSIONS:: Our findings support the model that ABCC6 is in the basolateral membrane, mediating the sinusoidal efflux of a metabolite from the hepatocytes to systemic circulation. © 2013 American Heart Association, Inc

Do You See What I Mean? Corticospinal Excitability During Observation of Culture-Specific Gestures

People all over the world use their hands to communicate expressively. Autonomous gestures, also known as emblems, are highly social in nature, and convey conventionalized meaning without accompanying speech. To study the neural bases of cross-cultural social communication, we used single pulse transcranial magnetic stimulation (TMS) to measure corticospinal excitability (CSE) during observation of culture-specific emblems. Foreign Nicaraguan and familiar American emblems as well as meaningless control gestures were performed by both a Euro-American and a Nicaraguan actor. Euro-American participants demonstrated higher CSE during observation of the American compared to the Nicaraguan actor. This motor resonance phenomenon may reflect ethnic and cultural ingroup familiarity effects. However, participants also demonstrated a nearly significant (p = 0.053) actor by emblem interaction whereby both Nicaraguan and American emblems performed by the American actor elicited similar CSE, whereas Nicaraguan emblems performed by the Nicaraguan actor yielded higher CSE than American emblems. The latter result cannot be interpreted simply as an effect of ethnic ingroup familiarity. Thus, a likely explanation of these findings is that motor resonance is modulated by interacting biological and cultural factors

Adherence to self-administered tuberculosis treatment in a high HIV-prevalence setting: a cross-sectional survey in Homa Bay, Kenya.

Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools

MUSE-ALMA Halos XI: Gas flows in the circumgalactic medium

The flow of gas into and out of galaxies leaves traces in the circumgalactic medium which can then be studied using absorption lines towards background quasars. We analyse 27 log(N_HI) > 18.0 HI absorbers at z = 0.2 to 1.4 from the MUSE-ALMA Halos survey with at least one galaxy counterpart within a line of sight velocity of +/-500 km s^{-1}. We perform 3D kinematic forward modelling of these associated galaxies to examine the flow of dense, neutral gas in the circumgalactic medium. From the VLT/MUSE, HST broadband imaging and VLT/UVES and Keck/HIRES high-resolution UV quasar spectroscopy observations, we compare the impact parameters, star-formation rates and stellar masses of the associated galaxies with the absorber properties. We find marginal evidence for a bimodal distribution in azimuthal angles for strong HI absorbers, similar to previous studies of the MgII and OVI absorption lines. There is no clear metallicity dependence on azimuthal angle and we suggest a larger sample of absorbers are required to fully test the relationship predicted by cosmological hydrodynamical simulations. A case-by-case study of the absorbers reveals that ten per cent of absorbers are consistent with gas accretion, up to 30 per cent trace outflows while the remainder trace gas in the galaxy disk, the intragroup medium and low-mass galaxies below the MUSE detection limit. Our results highlight that the baryon cycle directly affects the dense neutral gas required for star-formation and plays a critical role in galaxy evolution.Comment: 13 pages, 6 figures, 12 pages of appendix. Accepted for publication in MNRA

Shifting the Paradigm: The Putative Mitochondrial Protein ABCB6 Resides in the Lysosomes of Cells and in the Plasma Membrane of Erythrocytes

ABCB6, a member of the adenosine triphosphate–binding cassette (ABC) transporter family, has been proposed to be responsible for the mitochondrial uptake of porphyrins. Here we show that ABCB6 is a glycoprotein present in the membrane of mature erythrocytes and in exosomes released from reticulocytes during the final steps of erythroid maturation. Consistent with its presence in exosomes, endogenous ABCB6 is localized to the endo/lysosomal compartment, and is absent from the mitochondria of cells. Knock-down studies demonstrate that ABCB6 function is not required for de novo heme biosynthesis in differentiating K562 cells, excluding this ABC transporter as a key regulator of porphyrin synthesis. We confirm the mitochondrial localization of ABCB7, ABCB8 and ABCB10, suggesting that only three ABC transporters should be classified as mitochondrial proteins. Taken together, our results challenge the current paradigm linking the expression and function of ABCB6 to mitochondria

MUSE-ALMA Haloes IX: Morphologies and Stellar Properties of Gas-rich Galaxies

Understanding how galaxies interact with the circumgalactic medium (CGM) requires determining how galaxies morphological and stellar properties correlate with their CGM properties. We report an analysis of 66 well-imaged galaxies detected in HST and VLT MUSE observations and determined to be within $\pm$500 km s$^{-1}$ of the redshifts of strong intervening quasar absorbers at $0.2 \lesssim z \lesssim 1.4$ with H I column densities $N_{\rm H I}$ $>$ $10^{18}$ $\rm cm^{-2}$. We present the geometrical properties (S\'ersic indices, effective radii, axis ratios, and position angles) of these galaxies determined using GALFIT. Using these properties along with star formation rates (SFRs, estimated using the H$\alpha$ or [O II] luminosity) and stellar masses ($M_{*}$ estimated from spectral energy distribution fits), we examine correlations among various stellar and CGM properties. Our main findings are as follows: (1) SFR correlates well with $M_{*}$, and most absorption-selected galaxies are consistent with the star formation main sequence (SFMS) of the global population. (2) More massive absorber counterparts are more centrally concentrated and are larger in size. (3) Galaxy sizes and normalized impact parameters correlate negatively with $N_{\rm H I}$, consistent with higher $N_{\rm H I}$ absorption arising in smaller galaxies, and closer to galaxy centers. (4) Absorption and emission metallicities correlate with $M_{*}$ and sSFR, implying metal-poor absorbers arise in galaxies with low past star formation and faster current gas consumption rates. (5) SFR surface densities of absorption-selected galaxies are higher than predicted by the Kennicutt-Schmidt relation for local galaxies, suggesting a higher star formation efficiency in the absorption-selected galaxies.Comment: Accepted for publication in MNRAS, 25 pages, 19 figure

NSC23925, Identified in a High-Throughput Cell-Based Screen, Reverses Multidrug Resistance

Multidrug resistance (MDR) is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically.To identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1) but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of >10 microM NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors.The ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients

Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers

Multidrug resistance (MDR) remains a primary hindrance to curative cancer therapy. Thus, introduction of novel strategies to overcome MDR is of paramount therapeutic significance. Sequestration of chemotherapeutics in lysosomes is an established mechanism of drug resistance. Here, we show that MDR cells display a marked increase in lysosome number. We further demonstrate that imidazoacridinones (IAs), which are cytotoxic fluorochromes, undergo a dramatic compartmentalization in lysosomes because of their hydrophobic weak base nature. We hence developed a novel photoactivation-based pharmacological Trojan horse approach to target and eradicate MDR cancer cells based on photo-rupture of IA-loaded lysosomes and tumor cell lysis via formation of reactive oxygen species. Illumination of IA-loaded cells resulted in lysosomal photodestruction and restoration of parental cell drug sensitivity. Lysosomal photodestruction of MDR cells overexpressing the key MDR efflux transporters ABCG2, ABCB1 or ABCC1 resulted in 10- to 52-fold lower IC(50) values of various IAs, thereby restoring parental cell sensitivity. Finally, in vivo application of this photodynamic therapy strategy after i.v. injection of IAs in human ovarian tumor xenografts in the chorioallantoic membrane model revealed selective destruction of tumors and their associated vasculature. These findings identify lysosomal sequestration of IAs as an Achilles heel of MDR cells that can be harnessed to eradicate MDR tumor cells via lysosomal photodestruction