Substructural specificity and polyvalent carbohydrate recognition by the Entamoeba histolytica and rat hepatic N- acetylgalactosamine/galactose lectins

Both the Entamoeba histolytica lectin, a virulence factor for the causative agent of amebiasis, and the mammalian hepatic lectin bind to N-acetylgalactosamine (GalNAc) and galactose (Gal) nonreducing termini on oligosaccharides, with preference for GalNAc. Polyvalent GalNAc- derivatized neoglycoproteins have >1000-fold enhanced binding affinity for both lectins (Adler,P., Wood,S.J., Lee,Y.C., Lee,R.T., Petri,W.A.,Jr. and Schnaar,R.L.,1995, J. Biol. Chem ., 270, 5164-5171). Substructural specificity studies revealed that the 3-OH and 4-OH groups of GalNAc were required for binding to both lectins, whereas only the E.histolytica lectin required the 6-OH group. Whereas GalNAc binds with 4-fold lower affinity to the E.histolytica lectin than to the mammalian hepatic lectin, galactosamine and N-benzoyl galactosamine bind with higher affinity to the E. histolytica lectin. Therefore, a synthetic scheme for converting polyamine carriers to poly-N-acyl galactosamine derivatives (linked through the galactosamine primary amino group) was developed to test whether such ligands would bind the E.histolytica lectin with high specificity and high affinity. Contrary to expectations, polyvalent derivatives including GalN6lys5, GalN4desmosine, GalN4StarburstTMdendrimer, and GalN8StarburstTMdendrimer demonstrated highly enhanced binding to the mammalian hepatic lectin but little or no enhancement of binding to the E.histolytica lectin. We propose that the mammalian hepatic lectin binds with greatest affinity to GalNAc "miniclusters," which mimic branched termini of N-linked oligosaccharides, whereas the E.histolytica lectin binds most effectively to "maxiclusters," which may mimic more widely spaced GalNAc residues on intestinal mucins.      

Pseudomonas aeruginosa Reduces VX-809 Stimulated F508del-CFTR Chloride Secretion by Airway Epithelial Cells

BackgroundP. aeruginosa is an opportunistic pathogen that chronically infects the lungs of 85% of adult patients with Cystic Fibrosis (CF). Previously, we demonstrated that P. aeruginosa reduced wt-CFTR Cl secretion by airway epithelial cells. Recently, a new investigational drug VX-809 has been shown to increase F508del-CFTR Cl secretion in human bronchial epithelial (HBE) cells, and, in combination with VX-770, to increase FEV1 (forced expiratory volume in 1 second) by an average of 3-5% in CF patients homozygous for the F508del-CFTR mutation. We propose that P. aeruginosa infection of CF lungs reduces VX-809 + VX-770- stimulated F508del-CFTR Cl secretion, and thereby reduces the clinical efficacy of VX-809 + VX-770.ConclusionThe observation that P. aeruginosa reduces VX-809 and VX-809 + VX-770 stimulated F508del CFTR Cl secretion may explain, in part, why VX-809 + VX-770 has modest efficacy in clinical trials.     

Design Principles for Optimum Performance of Porous Carbons in Lithium–Sulfur Batteries

A series of experiments is presented that establishes for the first time the role of some of the key design parameters of porous carbons including surface area, pore volume, and pore size on battery performance. A series of hierarchical porous carbons is used as a model system with an open, 3D, interconnected porous framework and highly controlled porosity. Specifically, carbons with surface areas ranging from ≈500–2800 m² g^?1, pore volume from ≈0.6–5 cm³ g^?1, and pore size from micropores (≈1 nm) to large mesopores (≈30 nm) are synthesized and tested. At high sulfur loadings (≈80 wt% S), pore volume is more important than surface area with respect to sulfur utilization. Mesopore size, in the range tested, does not affect the sulfur utilization. No relationship between porosity and long‐term cycle life is observed. All systems fail after 200–300 cycles, which is likely due to the consumption of the LiNO₃ additive over cycling. Moreover, cryo‐scanning transmission electron microscopy imaging of these carbon–sulfur composites combined with X‐ray diffraction (XRD) provides further insights into the effect of initial sulfur distribution on sulfur utilization while also revealing the inadequacy of the indirect characterization techniques alone in reliably predicting distribution of sulfur within porous carbon matrices.     

Beards and the big city: displays of masculinity may be amplified under crowded conditions

Facial hair is a prominent secondary sexual trait, particularly given the importance of the face in interpersonal communication. Bizarrely by animal standards, men expend considerable effort every day trimming, waxing or shaving this androgen-dependent trait. Why some men shave this cue of masculinity off, and why women's preferences for facial hair vary so dramatically, remains largely unresolved. Using a large cross-cultural sample, we explore city- and nation-level variation in preferences for beards and in facial hair grooming patterns to test how economic and demographic conditions alter frequency-dependence in preferences for beardedness. We found that women's preferences for beards were strongest in countries with lower average incomes. Beards were most common in cities with larger populations, in countries where women express stronger preferences for facial hair and life expectancy was higher. Frequencies of non-beard facial hair styles (e.g. mustaches, goatees) were most common in large cities, but were unrelated to any demographic factors. Our results suggest a role for female choice in shaping large-scale patterns of facial hair grooming and highlight that under crowded conditions with high anonymity, displays of masculinity may be amplified.     

A Pseudomonas aeruginosa toxin that hijacks the host ubiquitin proteolytic system

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen chronically infecting the lungs of patients with chronic obstructive pulmonary disease (COPD), pneumonia, cystic fibrosis (CF), and bronchiectasis. Cif (PA2934), a bacterial toxin secreted in outer membrane vesicles (OMV) by P. aeruginosa, reduces CFTR-mediated chloride secretion by human airway epithelial cells, a key driving force for mucociliary clearance. The aim of this study was to investigate the mechanism whereby Cif reduces CFTR-mediated chloride secretion. Cif redirected endocytosed CFTR from recycling endosomes to lysosomes by stabilizing an inhibitory effect of G3BP1 on the deubiquitinating enzyme (DUB), USP10, thereby reducing USP10-mediated deubiquitination of CFTR and increasing the degradation of CFTR in lysosomes. This is the first example of a bacterial toxin that regulates the activity of a host DUB. These data suggest that the ability of P. aeruginosa to chronically infect the lungs of patients with COPD, pneumonia, CF, and bronchiectasis is due in part to the secretion of OMV containing Cif, which inhibits CFTR-mediated chloride secretion and thereby reduces the mucociliary clearance of pathogens.     

Purification and properties of inositol-1,4-bisphosphatase from bovine brain.

Inositol-1,4-bisphosphatase has been purified 13,000-fold from bovine brain supernatant. The enzyme is monomeric, with an apparent subunit Mr of 40,000. Maximal hydrolytic rates were observed in Tris buffer, pH 7.8, in the presence of 9 mM-Mg2+. The enzyme acted as a 1-phosphatase, hydrolysing both inositol 1,4-bisphosphate [Ins(1,4)P2] (Km 0.04 mM) and inositol 1,3,4-trisphosphate [Ins(1,3,4)P3] (Km 0.5 mM) to inositol 4-phosphate and inositol 3,4-bisphosphate respectively. Li+ inhibited the hydrolysis of both substrates in an uncompetitive manner, with apparent Ki values of 9.63 mM and 0.46 mM for Ins(1,4)P2 and Ins(1,3,4)P3 respectively.     

Contest competition and men's facial hair: beards may not provide advantages in combat

In contemporary human societies, where direct male-male competition is reduced compared to ancestral societies, sporting competitions remain an avenue for status acquisition via intra-sexual competition. Beards are the most visually salient and sexually dimorphic of men's secondary sexual traits and play a strong role in communicating masculinity, dominance and aggressiveness intra-sexually. Hypotheses have been advanced that beards provide advantages in intra-sexual combat, as protective organs and honest signals of fighting ability. Here we provide the first test of these hypotheses using data from professional mixed martial arts fighters competing in the Ultimate Fighting Championship. We explored whether secondary sexual traits (height, weight, beardedness), fighting stance (southpaw, orthodox), arm reach and past contest experiences impact on contest outcomes. If beards function as protective organs, bearded fighters should succumb to fewer knock-outs, and hence protection to injuries to the jaw, fewer abrasions and lacerations to the face and brain damage than clean-shaven fighters. Alternatively, if beards signal fighting ability then bearded fighters should win more fights. We found no evidence that beardedness was associated with fewer losses by knock-out or greater fighter ability. While fighters with longer reaches won more fights, neither stance nor past experience influenced fight outcomes. We suggest that beards represent dishonest signals of formidability that may serve to curtail the escalation of intra-sexual conflict through intimidation rather than providing advantages in direct combat.