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Predictions strongly influence perception. However, the neurophysiological processes that implement predictions remain underexplored. It has been proposed that high- and low-frequency neuronal oscillations act as carriers of sensory evidence and top-down predictions, respectively (von Stein and Sarnthein 2000; Bastos et al. 2012). However, evidence for the latter hypothesis remains scarce. In particular, it remains to be shown whether slow prestimulus alpha oscillations in task-relevant brain regions are stronger in the presence of predictions, whether they influence early categorization processes, and whether this interplay indeed boosts perception. Here, we directly address these questions by manipulating subjects' prior expectations about the identity of visually presented letters while collecting magnetoencephalographic recordings. We find that predictions lead to increased prestimulus alpha oscillations in a multisensory network representing grapheme/phoneme associations. Furthermore, alpha power interacts with stimulus degradation and top-down expectations to predict visibility ratings, and correlates with the amplitude of early sensory components (P1/N1m complex), suggesting a role in the selective amplification of predicted information. Our results thus indicate that low-frequency alpha oscillations can serve as a mechanism to carry and test sensory predictions about letters.

Typically, similar to 0.1% of the total number of olfactory sensory neurons (OSNs) in the main olfactory epithelium express the same odorant receptor (OR) in a singular fashion and their axons coalesce into homotypic glomeruli in the olfactory bulb. Here, we have dramatically increased the total number of OSNs expressing specific cloned OR coding sequences by multimerizing a 21-bp sequence encompassing the predicted homeodomain binding site sequence, TAATGA, known to be essential in OR gene choice. Singular gene choice is maintained in these "MouSensors.'' In vivo synaptopHluorin imaging of odor-induced responses by known M71 ligands shows functional glomerular activation in an M71 MouSensor. Moreover, a behavioral avoidance task demonstrates that specific odor detection thresholds are significantly decreased in multiple transgenic lines, expressing mouse or human ORs. We have developed a versatile platform to study gene choice and axon identity, to create biosensors with great translational potential, and to finally decode human olfaction.

A survey of nearly two hundred reports shows that rapid estrogenic actions can be detected across a range of kinds of estrogens, a range of doses, on a wide range of tissue, cell and ion channel types. Striking is the fact that preparations of estrogenic agents that do not permeate the cell membrane almost always mimic the actions of the estrogenic agents that do permeate the membrane. All kinds of estrogens, ranging from natural ones, through receptor modulators, endocrine disruptors, phytoestrogens, agonists, and antagonists to novel G-1 and SIX, have been reported to be effective. For actions on specific types of ion channels, the possibility of opposing actions, in different cases, is the rule, not the exception. With this variety there is no single, specific action mechanism for estrogens per se, although in some cases estrogens can act directly or via some signaling pathways to affect ion channels. We infer that estrogens can bind a large number of substrates/receptors at the membrane surface. As against the variety of subsequent routes of action, this initial step of the estrogen's binding action is the key. (C) 2016 Elsevier Inc. All rights reserved.

Factors constraining the structure of food webs can be investigated by comparing classes of ecosystems. We find that pelagic ecosystems, those based on one-celled primary producers, have longer food chains than terrestrial ecosystems. Yet pelagic ecosystems have lower primary productivity, contrary to the hypothesis that greater energy flows permit higher trophic levels. We hypothesize that longer food chain length in pelagic ecosystems, compared with terrestrial ecosystems, is associated with smaller pelagic animal body size permitting more rapid trophic energy transfer. Assuming negative allometric dependence of biomass production rate on body mass at each trophic level, the lowest three pelagic animal trophic levels are estimated to add biomass more rapidly than their terrestrial counterparts by factors of 12, 4.8, and 2.6. Pelagic animals consequently transport primary production to a fifth trophic level 50-190 times more rapidly than animals in terrestrial webs. This difference overcomes the approximately fivefold slower pelagic basal productivity, energetically explaining longer pelagic food chains. In addition, ectotherms, dominant at lower pelagic animal trophic levels, have high metabolic efficiency, also favoring higher rates of trophic energy transfer in pelagic ecosystems. These two animal trophic flow mechanisms imply longer pelagic food chains, reestablishing an important role for energetics in food web structure.

Despite the extensive use of doxycycline in tetracycline-inducible rodent models, little is known regarding its stability in feed or water or the most effective route or dose. We assessed the concentrations of doxycycline in reverse-osmosis-purified (RO; pH 6.0) and acidified RO (pH 2.6) water in untinted or green-tinted bottles. Doxycycline remained stable in all groups for 7 d and in acidified water in untinted bottles for 14 d. Fungal growth occurred in nonacidified water in tinted and untinted bottles by 12 and 14 d, respectively, and in tinted bottles containing acidified water on day 14, but not in untinted bottles with acidified water. Doxycycline concentrations were also assessed before and at various points after the pelleting of feed from 2 vendors. Each batch was divided for storage at 4 degrees C, at room temperature, or within ventilated mouse isolator cages and then sampled monthly for 6 mo. Drying caused the greatest decline in doxycycline concentration, whereas.-irradiation plus shipping and storage condition had minimal effect. Two mouse lines with tetracycline-inducible promoters received 25, 150, or 467 mu g/mL or 2 mg/mL doxycycline in water and 200 or 625 ppm in feed before analysis of GFP expression. GFP was expressed in Rosa-rtTA2 mice at 150 mu g/mL, whereas Cags-rtTA3 mice required 25 mu g/mL. These studies indicate that 1) doxycycline-compounded feed can be handled in the same manner as standard rodent feed, 2) tinted water bottles are not necessary for maintaining drug concentrations, and 3) concentrations lower than those used typically may be effective in lines with tetracycline-inducible promoters.

Although the intracellular trafficking system is integral to most physiologic activities, its role in mediating immune responses to infection has remained elusive. Here, we report that infected bladder epithelial cells (BECs) mobilized the exocyst complex, a powerful exporter of subcellular vesicles, to rapidly expel intracellular bacteria back for clearance. Toll-like receptor (TLR) 4 signals emanating from bacteria-containing vesicles (BCVs) were found to trigger K33-linked polyubiquitination of TRAF3 at Lys168, which was then detected by RalGDS, a guanine nucleotide exchange factor (GEF) that precipitated the assembly of the exocyst complex. Although this distinct modification of TRAF3 served to connect innate immune signaling to the cellular trafficking apparatus, it crucially ensured temporal and spatial accuracy in determining which among the many subcellular vesicles was recognized and selected for expulsion in response to innate immune signaling.

Phenotypic screens allow the identification of small molecules with promising anticancer activity, but the difficulty in characterizing the mechanism of action of these compounds in human cells often undermines their value as drug leads. Here, we used a loss-of-function genetic screen in human haploid KBM7 cells to discover the mechanism of action of the anticancer natural product ophiobolin A (OPA). We found that genetic inactivation of de novo synthesis of phosphatidylethanolamine (PE) mitigates OPA cytotoxicity by reducing cellular PE levels. OPA reacts with the ethanolamine head group of PE in human cells to form pyrrole-containing covalent cytotoxic adducts and these adducts lead to lipid bilayer destabilization. Our characterization of this unusual cytotoxicity mechanism, made possible by unbiased genetic screening in human cells, suggests that the selective antitumor activity displayed by OPA may be due to altered membrane PE levels in cancer cells.

The Chlamydomonas genome has been sequenced, assembled, and annotated to produce a rich resource for genetics and molecular biology in this well-studied model organism. However, the current reference genome contains similar to 1000 blocks of unknown sequence ('N-islands'), which are frequently placed in introns of annotated gene models. We developed a strategy to search for previously unknown exons hidden within such blocks, and determine the sequence, and exon/intron boundaries, of such exons. These methods are based on assembly and alignment of short cDNA and genomic DNA reads, completely independent of prior reference assembly or annotation. Our evidence indicates that a substantial proportion of the annotated intronic N-islands contain hidden exons. For most of these, our algorithm recovers full exonic sequence with associated splice junctions and exon-adjacent intronic sequence. These new exons represent de novo sequence generally present nowhere in the assembled genome, and the added sequence improves evolutionary conservation of the predicted encoded peptides.

Purpose: Surgical management of upper tract urothelial carcinoma requires kidney and ureter removal, compromising renal function. Nonsurgical alternatives have potentially prohibitive safety concerns. We examined the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular targeted photodynamic therapy in a porcine model. We also report the efficacy of WST11 vascular targeted photodynamic therapy in a murine model. Materials and Methods: After receiving approval we performed a total of 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4 mg/kg) followed by 10-minute laser illumination was done via percutaneous access or a retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology, which were evaluated at several postablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy. Results: At 24 hours 50 mW/cm laser fluence produced superficial necrosis of the ureter. Deeper necrosis penetrating the muscularis propria or adventitia was produced by treatment with 200 mW/cm in the ureter and the renal pelvis. At 4 weeks superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis or abnormality of laboratory testing was noted up to 4 weeks. Of the mice 80% had no evidence of tumor 19 days after WST11 vascular targeted photodynamic therapy. Conclusions: Urothelial cell carcinoma appears to be sensitive to WST11 vascular targeted photodynamic therapy. The depth of WST11 vascular targeted photodynamic therapy treatment effects can be modulated in a dose dependent manner by titrating light intensity. Moreover, when applied to the porcine upper urinary tract, this treatment modality is feasible via antegrade and retrograde access.

It is well established that danger information can be transmitted by ants through relatively small distances, provoking either a state of alarm when they move away from potentially dangerous stimulus, or charge toward it aggressively. There is almost no knowledge if danger information can be transmitted along large distances. In this paper, we abduct leaf cutting ants of the species Atta insularis while they forage in their natural environment at a certain point of the foraging line, so ants make a "U" turn to escape from the danger zone and go back to the nest. Our results strongly suggest that those ants do not transmit "danger information" to other nestmates marching towards the abduction area. The individualistic behavior of the ants returning from the danger zone results in a depression of the foraging activity due to the systematic sacrifice of non-informed individuals.