IRE1 sulfenylation by reactive oxygen species coordinates cellular stress signaling

Maintenance of cellular homeostasis is a fundamental aspect of stress-responsive signal transduction pathways. Specific signaling pathways are often considered, and certainly most often studied, in the context of responses to a specific endogenous or environmental stressor, but there are also fundamental questions that remain regarding how information about stress pathways with potentially overlapping inputs and/or outputs is optimally integrated and transduced by the cellular circuitry. In the current issue of Molecular Cell, Hourihan et al. (2016), combining molecular genetic and biochemical analysis in Caenorhabditis elegans and in mammalian cell systems, identify a mechanism by which IRE1, a principal regulator of the endoplasmic reticulum (ER) Unfolded Protein Response (UPR) (Walter and Ron, 2011), also regulates a response to reactive oxygen species (ROS). Signaling through IRE1 to promote ER homeostasis and the response to oxidative stress appears to be mutually exclusive—that is, signaling one response turns off the other, and vice versa

Inhibition of Lithium-Sensitive Phosphatase BPNT-1 Causes Selective Neuronal Dysfunction in C. elegans

Lithium has been a mainstay for the treatment of bipolar disorder, yet the molecular mechanisms underlying its action remain enigmatic. Bisphosphate 3′-nucleotidase (BPNT-1) is a lithium-sensitive phosphatase that catalyzes the breakdown of cytosolic 3′-phosphoadenosine 5′-phosphate (PAP), a byproduct of sulfation reactions utilizing the universal sulfate group donor 3′-phosphoadenosine 5′-phosphosulfate (PAPS) [1–3]. Loss of BPNT-1 leads to the toxic accumulation of PAP in yeast and non-neuronal cell types in mice [4, 5]. Intriguingly, BPNT-1 is expressed throughout the mammalian brain [4], and it has been hypothesized that inhibition of BPNT-1 could contribute to the effects of lithium on behavior [5]. Here, we show that loss of BPNT-1 in Caenorhabditis elegans results in the selective dysfunction of two neurons, the bilaterally symmetric pair of ASJ chemosensory neurons. As a result, BPNT-1 mutants are defective in behaviors dependent on the ASJ neurons, such as dauer exit and pathogen avoidance. Acute treatment with lithium also causes dysfunction of the ASJ neurons, and we show that this effect is reversible and mediated specifically through inhibition of BPNT-1. Finally, we show that the selective effect of lithium on the nervous system is due in part to the limited expression of the cytosolic sulfotransferase SSU-1 in the ASJ neuron pair. Our data suggest that lithium, through inhibition of BPNT-1 in the nervous system, can cause selective toxicity to specific neurons, resulting in corresponding effects on behavior of C. elegans.National Institutes of Health (U.S.) (Grant GM084477

Forming Early-type Galaxies in Groups Prior to Cluster Assembly

We study a unique proto-cluster of galaxies, the supergroup SG1120-1202. We quantify the degree to which morphological transformation of cluster galaxies occurs prior to cluster assembly in order to explain the observed early-type fractions in galaxy clusters at z=0. SG1120-1202 at z~0.37 is comprised of four gravitationally bound groups that are expected to coalesce into a single cluster by z=0. Using HST ACS observations, we compare the morphological fractions of the supergroup galaxies to those found in a range of environments. We find that the morphological fractions of early-type galaxies (~60 %) and the ratio of S0 to elliptical galaxies (0.5) in SG1120-1202 are very similar to clusters at comparable redshift, consistent with pre-processing in the group environment playing the dominant role in establishing the observed early-type fraction in galaxy clusters.Comment: 5 pages, 2 figures, 2 tables. Accepted for publication in ApJ Letter

A Search for Young Stars in the S0 Galaxies of a Super-Group at z=0.37

We analyze Galaxy Evolution Explorer UV data for a system of four gravitationally bound groups at z = 0.37, SG1120, which is destined to merge into a Coma-mass cluster by z = 0, to study how galaxy properties may change during cluster assembly. Of the 38 visually classified S0 galaxies, with masses ranging from log (M *)[M ☉] ≈ 10-11, we detect only one in the near-UV (NUV) channel, a strongly star-forming S0 that is the brightest UV source with a measured redshift placing it in SG1120. Stacking the undetected S0 galaxies (which generally lie on or near the optical red sequence of SG1120) still results in no NUV/far-UV (FUV) detection (\u3c2σ). Using our limit in the NUV band, we conclude that for a rapidly truncating star formation rate, star formation ceased at least ~0.1-0.7 Gyr ago, depending on the strength of the starburst prior to truncation. With an exponentially declining star formation history over a range of timescales, we rule out recent star formation over a wide range of ages. We conclude that if S0 formation involves significant star formation, it occurred well before the groups were in this current pre-assembly phase. As such, it seems that S0 formation is even more likely to be predominantly occurring outside of the cluster environment

Review of the Surgical Approaches for Peyronie's Disease: Corporeal Plication and Plaque Incision with Grafting

The understanding and management of Peyronie's disease (PD) has improved but elucidating the exact etiology of the disease has yet to be achieved. In this paper, we review the historical and clinical aspects of PD. We focus on the evolution of surgical management for PD and review recent published articles that compare popular surgical techniques such as plication and plaque incision with vein graft. These two techniques have been reported to be equivalent with respect to patient satisfaction; however, each technique has its own advantages and disadvantages

Penile Corporeal Reconstruction during Difficult Placement of a Penile Prosthesis

For some patients with impotence and concomitant severe tunical/corporeal tissue fibrosis, insertion of a penile prosthesis is the only option to restore erectile function. Closing the tunica over an inflatable penile prosthesis in these patients can be challenging. We review our previous study which included 15 patients with severe corporeal or tunical fibrosis who underwent corporeal reconstruction with autologous rectus fascia to allow placement of an inflatable penile prosthesis. At a mean follow-up of 18 months (range 12 to 64), all patients had a prosthesis that was functioning properly without evidence of separation, herniation, or erosion of the graft. Sexual activity resumed at a mean time of 9 weeks (range 8 to 10). There were no adverse events related to the graft or its harvest. Use of rectus fascia graft for coverage of a tunical defect during a difficult penile prosthesis placement is surgically feasible, safe, and efficacious

Multicritical Points of Potts Spin Glasses on the Triangular Lattice

We predict the locations of several multicritical points of the Potts spin glass model on the triangular lattice. In particular, continuous multicritical lines, which consist of multicritical points, are obtained for two types of two-state Potts (i.e., Ising) spin glasses with two- and three-body interactions on the triangular lattice. These results provide us with numerous examples to further verify the validity of the conjecture, which has succeeded in deriving highly precise locations of multicritical points for several spin glass models. The technique, called the direct triangular duality, a variant of the ordinary duality transformation, directly relates the triangular lattice with its dual triangular lattice in conjunction with the replica method.Comment: 18 pages, 2, figure