Pit-bull reviewing, the pursuit of perfection and the victims of success

Forming synaptic connections of the appropriate strength between specific neurons is crucial for constructing neural circuits to control behavior. A recent paper in Neural Development describes the use of a synapse-specific label in Caenorhabditis elegans to implicate local UNC-6/netrin signaling in this developmental process. Thus, as well as their well known roles in cell migration and axon guidance, UNC-6/netrin signals distinguish an appropriate synaptic partner from other potential targets. See Research article: http://www.neuraldevelopment.com/content/6/1/28     

The Rabs: A family at the root of metazoan evolution

This paper is a response to Pecinka A, Fang W, Rehmsmeier M, Levy AA, Mittelsten Scheid, O: Polyploidization increases meiotic recombination frequency in Arabidopsis. BMC Biology 2011, 9:24. See research article at http://www.biomedcentral.com/1741-7007/9/24     

A novel deconvolution method for modeling UDP-N-acetyl-D-glucosamine biosynthetic pathways based on 13C mass isotopologue profiles under non-steady-state conditions

This article is a response to Wang and Luo. See correspondence article http://www.biomedcentral.com/1741-7007/10/30/ [WEBCITE] and the original research article http://www.biomedcentral.com/1741-7007/9/24 [WEBCITE].     

HIV takes double hit before entry

In the absence of a vaccine or a cure, identification of novel HIV-1 inhibitors remains important. A paper in Retrovirology describes a rationally designed bi-specific protein that irreversibly damages the viral envelope glycoprotein complex via a two-punch mechanism. In contrast to traditional drugs that inhibit essential steps in the viral life cycle at the cell surface or in the infected cells, this inhibitor cripples free virus in the absence of cells.See research article: http://www.retrovirology.com/content/9/1/104     

CCK-8S activates c-Fos in a dose-dependent manner in nesfatin-1 immunoreactive neurons in the paraventricular nucleus of the hypothalamus and in the nucleus of the solitary tract of the brainstem

Recently, a new neuropeptide, named nesfatin-1, was discovered. It has been reported that nesfatin-1 inhibits food intake after injection into the third ventricle as well as intraperitoneal (ip) injection. Cholecystokinin (CCK) is well established to play a role in the regulation of food intake. The aim of the study was to examine whether CCK-8S injected ip modulates neuronal activity in nesfatin-1 immunoreactive (ir) neurons localized in the PVN and in the nucleus of the solitary tract (NTS). Additionally, tyrosine hydroxylase-immunoreactivity (TH-ir) in the PVN was determined to assess the distribution of TH-ir fibers in relation to nesfatin-1-ir. Non-fasted male Sprague-Dawley rats received 6 or 10 µg CCK-8S/kg or vehicle solution (0.15 M NaCl; n = 4 all groups) ip. The number of c-Fos-ir neurons was determined in the PVN, arcuate nucleus (ARC), and NTS. Double staining procedure for nesfatin-1 and c-Fos revealed that CCK-8S increased significantly and in a dose-dependent manner the number of c-Fos positive nesfatin-1-ir neurons in the PVN ( 4-fold and 7-fold) and NTS ( 9-fold and 26-fold). Triple staining in the PVN showed a dose-dependent neuronal activation of nesfatin-1 neurons that were colocalized with CRF and oxytocin. Double labeling against nesfatin-1 and TH revealed that nefatin-1-ir neurons were encircled in a network of TH-ir fibers in the PVN. No effect on the number of c-Fos-ir neurons was observed in the ARC. These results suggest that the effects of CCK on the HPA axis and on food intake may, at least in part, be mediated by nesfatin-1-ir neurons in the PVN.     

Protein kinase C-α negatively regulates EGF-induced PLC- activity through direct phosphorylation

Phospholipase C- is a PLC isozyme that contains a CDC25 homology domain and a pair of RA domains in addition to a conserved PLC catalytic domain. PLC- is activated by both growth factors and GPCR ligands in a distinct manner. Growth factors such as EGF stimulate PLC- in an RA2 domain-dependent manner through Ras and Rap. On the other hand, several GPCR ligands that are linked with Ga₁₂ or Ga₁₃ can activate PLC- by associating with GTP-RhoA. GTP-RhoA binds with the region in the PLC- Y domain. Gs-linked ligands such as PGE1 and adrenaline stimulate PLC- by cAMP-dependent activation of Epac and Rap2B. PLC- is important for cardiac development and function. In addition, several lines of evidence indicate that PLC- promotes cell growth in an activity-dependent or -independent manner. In particular, PLC--dependent suppression of EGF receptor downregulation contributes to its growth promoting activity. Proper regulation of PLC- activity is essential for preventing tumor formation. Our previous report indicated that EGF-dependent ubiquitination of PLC- is required for the control of PLC--dependent cell growth. Recently, we found that PLC- is phosphorylated by growth factor stimulation, and this is another mechanism of the negative regulation. PLC- is phosphorylated by PKC-α upon stimulation with growth factors such as EGF and PDGF. The EGF-induced phosphorylation of PLC- was abolished by PKC inhibitors and by the expression of the dominant negative mutant of PKC-α. Furthermore, PKC-α was found to phosphorylate PLC- directly in vitro, suggesting that PLC- is a substrate of PKC-α in cells. In addition, PLC- was co-immunoprecipitated with PKC-α in an EGF-dependent manner. Immunocytochemical studies showed that PLC- co-localized with PKC-α in the plasma membrane after EGF stimulation. In addition, inhibition of PKC activity enhanced PLC--mediated PIP₂ hydrolysis, suggesting that PKC-α negatively regulates PLC- activity. Taken together, these results suggest for the first time that PLC- is regulated by PKC-α-dependent phosphorylation.     

The scent of your enemy is my friend? The acquisition of large carnivore scent by a smaller carnivore

Scent marking is critical to intraspecific communication in many mammal species, but little is known regarding its role in communication among different species. We used 4 years of motion-triggered video to document the use of scent marking areas—termed “community scrapes”—by pumas (Puma concolor) (http://www.momo-p.com/showdetail-e.php?movieid=momo160812pc01a) and other carnivore species. We found that gray foxes (Urocyon cinereoargenteus) routinely rubbed their cheeks on puma scrapes (http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc01a), and tested a series of hypotheses to determine its function. We found that gray foxes selected puma scrapes over other objects, and cheek rubbing by foxes was also correlated with how recently a puma had visited the scrape, suggesting that foxes were intent upon accumulating fresh puma scent. Cheek rubbing by foxes was not correlated with their breeding season or with how recently another fox had visited the site. Finally we found a cascading pattern in the occurrence of pumas, coyotes (Canis latrans) and gray foxes at community scrapes, suggesting that gray foxes may use puma scent to deter predation. This is the first published study to find evidence of a subordinate species using the scent of a dominant species to communicate with heterospecifics. The behavioral cascade we found in scent marking patterns also suggests that scent marking could be a mechanism that impacts the distribution and abundance of species. Additional videos pertaining to this article include http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc02a, and http://www.momo-p.com/showdetail-e.php?movieid=momo160812uc03a.     

Interspecific responses of wild African carnivores to odour of 3-mercapto-3-methylbutanol,a component of wildcat and leopard urine

The scent of 3-mercapto-3-methylbutanol (3-M-3-MB), a volatile component of leopard (Panthera pardus) and domestic cat (Felis silvestris catus) urine, released at about 10 ng/s from slow-release dispensers, elicited scent-marking from African civet (Civettictis civetta), small-spotted genet (Genetta genetta) and slender mongoose (Galerella sanguinea), as well as African wildcat (F. s. cafra). A female leopard was apparently repelled by the scent. The scent-marking and scent-rubbing by species other than African wildcats and leopards were unexpected and have important implications for the design of studies to investigate chemical communication between wild mammals and the use of camera traps to estimate animal numbers. Videos showing the behaviours referred to in this article are available at; http://www.momo-p.com/showdetail-e.php?movieid=momo161223fs01a; http://www.momo-p.com/showdetail-e.php?movieid=momo161223gs01a; http://www.momo-p.com/showdetail-e.php?movieid=momo161223gg01a.