Pigment Dispersing Factors and Their Cognate Receptors in a Crustacean Model, With New Insights Into Distinct Neurons and Their Functions

Pigment dispersing factors (PDFs, or PDHs in crustaceans) form a structurally related group of neuropeptides found throughout the Ecdysozoa and were first discovered as pigmentary effector hormones in crustaceans. In insects PDFs fulfill crucial neuromodulatory roles, most notably as output regulators of the circadian system, underscoring their central position in physiological and behavioral organization of arthropods. Intriguingly, decapod crustaceans express multiple isoforms of PDH originating from separate genes, yet their differential functions are still to be determined. Here, we functionally define two PDH receptors in the crab Carcinus maenas and show them to be selectively activated by four PDH isoforms: PDHR 43673 was activated by PDH-1 and PDH-2 at low nanomolar doses whilst PDHR 41189 was activated by PDH-3 and an extended 20 residue e-PDH. Detailed examination of the anatomical distribution of all four peptides and their cognate receptors indicate that they likely perform different functions as secreted hormones and/or neuromodulators, with PDH-1 and its receptor 43,673 implicated in an authentic hormonal axis. PDH-2, PDH-3, and e-PDH were limited to non-neurohemal interneuronal sites in the CNS; PDHR 41189 was largely restricted to the nervous system suggesting a neuromodulatory function. Notably PDH-3 and e-PDH were without chromatophore dispersing activity. This is the first report which functionally defines a PDHR in an endocrine system in a crustacean and to indicate this and other putative roles of this physiologically pivotal peptide group in these organisms. Thus, our findings present opportunities to further examine the endocrine and circadian machinery in this important arthropod phylum

The effect of lattice temperature on surface damage in fused silica optics

We examine the effect of lattice temperature on the probability of surface damage initiation for 355nm, 7ns laser pulses for surface temperatures below the melting point to temperatures well above the melting point of fused silica. At sufficiently high surface temperatures, damage thresholds are dramatically reduced. Our results indicate a temperature activated absorption and support the idea of a lattice temperature threshold of surface damage. From these measurements, we estimate the temperature dependent absorption coefficient for intrinsic silica

The Role of the Mucus Barrier in Digestion

Mucus forms a protective layer across a variety of epithelial surfaces. In the gastrointestinal (GI) tract, the barrier has to permit the uptake of nutrients, while excluding potential hazards, such as pathogenic bacteria. In this short review article, we look at recent literature on the structure, location, and properties of the mammalian intestinal secreted mucins and the mucus layer they form over a wide range of length scales. In particular, we look at the structure of the gel-forming glycoprotein MUC2, the primary intestinal secreted mucin, and the influence this has on the properties of the mucus layer. We show that, even at the level of the protein backbone, MUC2 is highly heterogeneous and that this is reflected in the networks it forms. It is evident that a combination of charge and pore size determines what can diffuse through the layer to the underlying gut epithelium. This information is important for the targeted delivery of bioactive molecules, including nutrients and pharmaceuticals, and for understanding how GI health is maintained

Epicure: a European epidemiological study of patients with an advanced or metastatic Urothelial Carcinoma (UC) having progressed to a platinum-based chemotherapy

Background: Platinum-based systemic chemotherapy is considered the backbone for management of advanced urothelial carcinomas. However there is a lack of real world data on the use of such chemotherapy regimens, on patient profiles and on management after treatment failure. Methods: Fifty-one randomly selected physicians from 4 European countries registered 218 consecutive patients in progression or relapse following a first platinum-based chemotherapy. Patient characteristics, tumor history and treatment regimens, as well as the considerations of physicians on the management of urothelial carcinoma were recorded. Results: A systemic platinum-based regimen had been administered as the initial chemotherapy in 216 patients: 15 in the neoadjuvant setting, 61 in adjuvant therapy conditions, 137 in first-line advanced setting and 3 in other conditions. Of these patients, 76 (35 %) were initially considered as cisplatin-unfit, mainly because of renal impairment (52 patients). After platinum failure, renal impairment was observed in 44 % of patients, ECOG Performance Status ≥ 2 in 17 %, hemoglobinemia 30 % patients). The most frequent all-settings second anticancer therapy regimen was vinflunine (70 % of single-agent and 42 % of all subsequent treatments), the main reasons evoked by physicians (>1 out of 4) being survival benefit, safety and phase III evidence. Conclusion: In this daily practice experience, a majority of patients with urothelial carcinoma previously treated with a platinum-based therapy received a second chemotherapy regimen, most often a single agent after an initial chemotherapy in the advanced setting and preferably a cytotoxic combination after a neoadjuvant or adjuvant chemotherapy. Performance Status and prior response to chemotherapy were the main drivers of further treatment decisions

Structure of the silicon vacancy in 6H-SiC after annealing identified as the carbon vacancy–carbon antisite pair

We investigated radiation-induced defects in neutron-irradiated and subsequently annealed 6H-silicon carbide (SiC) with electron paramagnetic resonance (EPR), the magnetic circular dichroism of the absorption (MCDA), and MCDA-detected EPR (MCDA-EPR). In samples annealed beyond the annealing temperature of the isolated silicon vacancy we observed photoinduced EPR spectra of spin S=1 centers that occur in orientations expected for nearest neighbor pair defects. EPR spectra of the defect on the three inequivalent lattice sites were resolved and attributed to optical transitions between photon energies of 999 and 1075 meV by MCDA-EPR. The resolved hyperfine structure indicates the presence of one single carbon nucleus and several silicon ligand nuclei. These experimental findings are interpreted with help of total energy and spin density data obtained from the standard local-spin density approximation of the density-functional theory, using relaxed defect geometries obtained from the self-consistent charge density-functional theory based tight binding scheme. We have checked several defect models of which only the photoexcited spin triplet state of the carbon antisite–carbon vacancy pair (CSi-VC) in the doubly positive charge state can explain all experimental findings. We propose that the (CSi-VC) defect is formed from the isolated silicon vacancy as an annealing product by the movement of a carbon neighbor into the vacancy

Code Reuse in Open Source Software

Code reuse is a form of knowledge reuse in software development that is fundamental to innovation in many fields. However, to date there has been no systematic investigation of code reuse in open source software projects. This study uses quantitative and qualitative data gathered from a sample of six open source software projects to explore two sets of research questions derived from the literature on software reuse in firms and open source software development. We find that code reuse is extensive across the sample and that open source software developers, much like developers in firms, apply tools that lower their search costs for knowledge and code, assess the quality of software components, and have incentives to reuse code. Open source software developers reuse code because they want to integrate functionality quickly, because they want to write preferred code, because they operate under limited resources in terms of time and skills, and because they can mitigate development costs through code reuse

Reconsidering the Tribal-State Compact Process

This essay evaluates the tribal‐state compact process, as one of several alternative, nonadversarial processes, warranting attention. It argues that, because of its binding character and relatively low cost (in contrast to litigation), and because it is based in the idea of tribes and states exhibiting mutual respect, the compact process is an advanced version of negotiation and bargaining that tribes and states should consider where appropriate

The Geozoic Supereon

Geological time units are the lingua franca of earth sciences: they are a terminological convenience, a vernacular of any geological conversation, and a prerequisite of geo-scientific writing found throughout in earth science dictionaries and textbooks. Time units include terms formalized by stratigraphic committees as well as informal constructs erected ad hoc to communicate more efficiently. With these time terms we partition Earth’s history into utilitarian and intuitively understandable time segments that vary in length over seven orders of magnitude: from the 225-year-long Anthropocene (Crutzen and Stoermer, 2000) to the ,4-billion-year-long Precambrian (e.g., Hicks, 1885; Ball, 1906; formalized by De Villiers, 1969)

Is post-trabeculectomy hypotony a risk factor for subsequent failure? A case control study

BACKGROUND: Ocular hypotony results in an increased break down of the blood-aqueous barrier and an increase in inflammatory mediator release. We postulate that this release may lead to an increased risk of trabeculectomy failure through increased bleb scarring. This study was designed to try to address the question if hypotony within one month of trabeculectomy for Primary Open Angle Glaucoma (POAG), is a risk factor for future failure of the filter. METHODS: We performed a retrospective, case notes review, of patients who underwent trabeculectomy for POAG between Jan 1995 and Jan 1996 at our hospital. We identified those with postoperative hypotony within 1 month of surgery. Hypotony was defined as an intraocular pressure (IOP) < 8 mmHg or an IOP of less than 10 mmHg with choroidal detachment or a shallow anterior chamber. We compared the survival times of the surgery in this group with a control group (who did not suffer hypotony as described above), over a 5 year period. Failure of trabeculectomy was defined as IOP > 21 mmHg, or commencement of topical antihypertensives or repeat surgery. RESULTS: 97 cases matched our inclusion criteria, of these 38 (39%) experienced hypotony within 1 month of surgery. We compared the survival times in those patients who developed hypotony with those who did not using the log-rank test. This data provided evidence of a difference (P = 0.0492) with patients in the hypotony group failing more rapidly than the control group. CONCLUSION: Early post-trabeculectomy hypotony (within 1 month) is associated with reduced survival time of blebs