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Acid-sensing ion channels (ASICs) are proton-gated cation channels that detect and signal increases in proton concentration. ASIC1a and ASIC3 play a role in pain sensation associated with extracellular acidification. There are few selective modulators of ASIC3, including the tetrapeptide RFamide RPRFa, which slows the acute desensitization of ASIC3. Here we describe the peptide WRPRFa as the most potent ASIC3 activator to date and a more effective pharmacological tool. WRPRFa enhances the pH sensitivity of ASIC3 and effectively removes acute desensitization. Additionally, we demonstrate that ASIC3 can undergo tachyphylaxis at very acidic pH, which is accelerated by WRPRFa. Our work characterizes a selective and effective in vitro tool to study the interaction of RFamides and ASICs, and by extension gating mechanisms of ASIC3. Acid-sensing ion channels (ASICs) are crucial in pain sensation linked to extracellular acidification, yet selective modulators for ASIC3 remain limited. Here, the authors identify WRPRFa, a selective and potent peptide modulator of ASIC3 gating, that enhances ASIC3 pH sensitivity and removes acute desensitization, offering a valuable tool for studying ASIC3 gating mechanisms.

Pancreatic cancer typically spreads rapidly and has poor survival rates. Here, we report that the calcium-activated chloride channel TMEM16A is a biomarker for pancreatic cancer with a poor prognosis. TMEM16A is up-regulated in 75% of cases of pancreatic cancer and high levels of TMEM16A expression are correlated with low patient survival probability. TMEM16A up-regulation is associated with the ligand-dependent EGFR signaling pathway. In vitro, TMEM16A is required for EGF-induced store-operated calcium entry essential for pancreatic cancer cell migration. TMEM16A also has a profound impact on phosphoproteome remodeling upon EGF stimulation. Moreover, molecular actors identified in this TMEM16A-dependent EGFR-induced calcium signaling pathway form a gene set that makes it possible not only to distinguish neuro-endocrine tumors from other forms of pancreatic cancer, but also to subdivide the latter into three clusters with distinct genetic profiles that could reflect their molecular underpinning.

2'-4' Dinitrofluorobenzene (DNFB) induced contact hypersensitivity is an established model of contact sensitivity and leukocyte migration. Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) deficient mice were used to examine the role of PECAM-1 in the migration capacity of several different leukocyte populations after primary and secondary application. γδ T lymphocytes, granulocytes, and Natural Killer cells were most affected by PECAM-1 deficiency at the primary site of application. γδ T lymphocytes, granulocytes, DX5+ Natural Killer cells, and, interestingly, effector CD4+ T lymphocytes were most affected by the loss of PECAM-1 at the secondary site of application. PECAM-1 is used by many leukocyte populations for migration, but there are clearly differential effects on the usage by each subset. Further, the overall kinetics of each population varied between primary and secondary application, with large relative increases in γδ T lymphocytes during the secondary response.

BACKGROUND: 2’-4’ Dinitrofluorobenzene (DNFB) induced contact hypersensitivity is an established model of contact sensitivity and leukocyte migration. Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1) deficient mice were used to examine the role of PECAM-1 in the migration capacity of several different leukocyte populations after primary and secondary application. RESULTS: γδ T lymphocytes, granulocytes, and Natural Killer cells were most affected by PECAM-1 deficiency at the primary site of application. γδ T lymphocytes, granulocytes, DX5+ Natural Killer cells, and, interestingly, effector CD4+ T lymphocytes were most affected by the loss of PECAM-1 at the secondary site of application. CONCLUSIONS: PECAM-1 is used by many leukocyte populations for migration, but there are clearly differential effects on the usage by each subset. Further, the overall kinetics of each population varied between primary and secondary application, with large relative increases in γδ T lymphocytes during the secondary response.

The changing landscape of higher education has challenged institutions to find new revenue sources and to make fiscal adaptations more along the lines of privatized businesses. Public institutions over the past thirty years have seen declining public funding and increased enrollments. As a result, areas of external funding such as development appear to have taken on an increasingly centralized role in the financial management of institutions. Given the changing state of affairs in higher education and the importance of fundraising, this analysis proposes new consideration be given to collaboration on development efforts across institutional professional cultures. Specifically, how can development professionals strategically utilize faculty members in campaigns and initiatives in order for mutually beneficial avenues of collaboration to be created? How can faculty members and development officers collaboration on campaigns mutually benefit professional interests while positively influencing institutional initiatives and programs? What are the barriers to creating a collaborative relationship and can they be overcome? What does a potential working relationship among faculty members and development officers mean for each professional group and public institutions as a whole? Is it possible to infuse an operational culture of appreciation regarding development into the modern public institution?

More than one third of the human brain is devoted to the processes of seeing — vision is after all the main way in which we gather information about the world. But human vision is a dynamic process during which the eyes continually sample the environment. Where most books on vision consider it as a passive activity, this book focuses on vision as an ‘active’ process. It goes beyond most accounts of vision where the focus is on seeing, to provide an account of seeing AND looking. The book starts by pointing out the weaknesses in our traditional approaches to vision and the reason we need this new approach. It then gives a thorough description of basic details of the visual and oculomotor systems necessary to understand active vision. The book goes on to show how this approach can give a new perspective on visual attention, and how the approach has progressed in the areas of visual orienting, reading, visual search, scene perception, and neuropsychology. Finally, the book summarizes progress by showing how this approach sheds new light on the old problem of how we maintain perception of a stable visual world.

Tracking changes in seabird populations from remote Arctic regions using traditional monitoring techniques is financially and logistically challenging, leading to limited information on historical population trends. In this pilot study, we use a novel application of paleolimnological proxies to track environmental change using bird nests. Specifically, we examine long-term population dynamics of the Northern Common Eider ( Somateria mollissima borealis ), a philopatric sea duck. Eider nests from the Canadian sub-Arctic were sampled and radioisotopically dated, indicating that eiders have been nesting here since the 1800s. To assess the applicability of paleoecological proxies in nests to monitor environmental changes and long-term eider population dynamics, we examined changes in diatom species composition, shifts in the abundance of siliceous proxies (i.e., diatoms, chrysophyte cysts, phytoliths, protozoan plates), visible reflectance spectroscopy-inferred chlorophyll a (VRS-chla), stable nitrogen isotopes, and a selection of metal(loid)s. Warmer post-Little Ice Age conditions after the mid-19 th century, together with higher eider occupation rates, promoted the proliferation of diatoms and other siliceous indicators. Declining eider populations during the industrial era, likely due to increased hunting pressures, was indicated by declines in δ 15 N values and relative abundances of diatom taxa typically associated with higher nutrients and/or moisture. Increasing concentrations of metals (i.e., Zn and Cd), δ 15 N values, and VRS-chla, which are positively associated with eider nesting activity, provided further support that eider numbers increased during the latter part of the 20 th century. Our study shows that the accumulated vegetative and peat material from eider nests can provide a powerful tool to track historical bird population dynamics in ways that traditional, more recent, population monitoring methods cannot. Collectively, these methods can contribute insights to guide conservation decisions of this harvested species and other under-surveyed species.

Chemical investigation of an undescribed Australian fungus, Aspergillus nanangensis , led to the identification of the nanangenines – a family of seven new and three previously reported drimane sesquiterpenoids. The structures of the nanangenines were elucidated by detailed spectroscopic analysis supported by single crystal X-ray diffraction studies. The compounds were assayed for in vitro activity against bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines.

[This corrects the article DOI: 10.1371/journal.pone.0332605.].