Gauge symmetry and W-algebra in higher derivative systems

The problem of gauge symmetry in higher derivative Lagrangian systems is discussed from a Hamiltonian point of view. The number of independent gauge parameters is shown to be in general {\it{less}} than the number of independent primary first class constraints, thereby distinguishing it from conventional first order systems. Different models have been considered as illustrative examples. In particular we show a direct connection between the gauge symmetry and the W-algebra for the rigid relativistic particle.Comment: 1+22 pages, 1 figure, LaTeX, v2; title changed, considerably expanded version with new results, to appear in JHE

Release of Lungworm Larvae from Snails in the Environment: Potential for Alternative Transmission Pathways

Background: Gastropod-borne parasites may cause debilitating clinical conditions in animals and humans following the consumption of infected intermediate or paratenic hosts. However, the ingestion of fresh vegetables contaminated by snail mucus and/or water has also been proposed as a source of the infection for some zoonotic metastrongyloids (e.g., Angiostrongylus cantonensis). In the meantime, the feline lungworms Aelurostrongylus abstrusus and Troglostrongylus brevior are increasingly spreading among cat populations, along with their gastropod intermediate hosts. The aim of this study was to assess the potential of alternative transmission pathways for A. abstrusus and T. brevior L3 via the mucus of infected Helix aspersa snails and the water where gastropods died. In addition, the histological examination of snail specimens provided information on the larval localization and inflammatory reactions in the intermediate host. Methodology/Principal Findings: Twenty-four specimens of H. aspersa received ~500 L1 of A. abstrusus and T. brevior, and were assigned to six study groups. Snails were subjected to different mechanical and chemical stimuli throughout 20 days in order to elicit the production of mucus. At the end of the study, gastropods were submerged in tap water and the sediment was observed for lungworm larvae for three consecutive days. Finally, snails were artificially digested and recovered larvae were counted and morphologically and molecularly identified. The anatomical localization of A. abstrusus and T. brevior larvae within snail tissues was investigated by histology. L3 were detected in the snail mucus (i.e., 37 A. abstrusus and 19 T. brevior) and in the sediment of submerged specimens (172 A. abstrusus and 39 T. brevior). Following the artificial digestion of H. aspersa snails, a mean number of 127.8 A. abstrusus and 60.3 T. brevior larvae were recovered. The number of snail sections positive for A. abstrusus was higher than those for T. brevior. Conclusions: Results of this study indicate that A. abstrusus and T. brevior infective L3 are shed in the mucus of H. aspersa or in water where infected gastropods had died submerged. Both elimination pathways may represent alternative route(s) of environmental contamination and source of the infection for these nematodes under field conditions and may significantly affect the epidemiology of feline lungworms. Considering that snails may act as intermediate hosts for other metastrongyloid species, the environmental contamination by mucus-released larvae is discussed in a broader context

Conserved Daily Transcriptional Programs in Carica papaya

Most organisms have internal circadian clocks that mediate responses to daily environmental changes in order to synchronize biological functions to the correct times of the day. Previous studies have focused on plants found in temperate and sub-tropical climates, and little is known about the circadian transcriptional networks of plants that typically grow under conditions with relatively constant day lengths and temperatures over the year. In this study we conducted a genomic and computational analysis of the circadian biology of Carica papaya, a tropical tree. We found that predicted papaya circadian clock genes cycle with the same phase as Arabidopsis genes. The patterns of time-of-day overrepresentation of circadian-associated promoter elements were nearly identical across papaya, Arabidopsis, rice, and poplar. Evolution of promoter structure predicts the observed morning- and evening-specific expression profiles of the papaya PRR5 paralogs. The strong conservation of previously identified circadian transcriptional networks in papaya, despite its tropical habitat and distinct life-style, suggest that circadian timing has played a major role in the evolution of plant genomes, consistent with the selective pressure of anticipating daily environmental changes. Further studies could exploit this conservation to elucidate general design principles that will facilitate engineering plant growth pathways for specific environments

Regulation of rat intrapulmonary arterial tone by arachidonic acid and prostaglandin E2 during hypoxia

Aims Arachidonic acid (AA) and its metabolites, prostaglandins (PG) are known to be involved in regulation of vascular homeostasis including vascular tone and vessel wall tension, but their potential role in Hypoxic pulmonary vasoconstriction (HPV) remains unclear. In this study, we examined the effects of AA and PGE2 on the hypoxic response in isolated rat intrapulmonary arteries (IPAs). Methods and Results We carried out the investigation on IPAs by vessel tension measurement. Isotetrandrine (20 µM) significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. Both indomethacin (100 µM) and NS398 attenuated KPSS-induced vessel contraction and phase I, phase IIb and phase IIc of HPV, implying that COX-2 plays a primary role in the hypoxic response of rat IPAs. PGE2 alone caused a significant vasoconstriction in isolated rat IPAs. This constriction is mediated by EP4. Blockage of EP4 by L-161982 (1 µM) significantly inhibited phase I, phase IIb and phase IIc of hypoxic vasoconstriction. However, AH6809 (3 µM), an antagonist of EP1, EP2, EP3 and DP1 receptors, exerted no effect on KPSS or hypoxia induced vessel contraction. Increase of cellular cAMP by forskolin could significantly reduce KPSS-induced vessel contraction and abolish phase I, phase II b and phase II c of HPV. Conclusion Our results demonstrated a vasoconstrictive effect of PGE2 on rat IPAs and this effect is via activation of EP4. Furthermore, our results suggest that intracellular cAMP plays dual roles in regulation of vascular tone, depending on the spatial distribution of cAMP and its coupling with EP receptor and Ca2+ channels

The efficacy of chemotherapy is limited by intratumoral senescent cells expressing PD-L2

Chemotherapy often generates intratumoral senescent cancer cells that strongly modify the tumor microenvironment, favoring immunosuppression and tumor growth. We discovered, through an unbiased proteomics screen, that the immune checkpoint inhibitor programmed cell death 1 ligand 2 (PD-L2) is highly upregulated upon induction of senescence in different types of cancer cells. PD-L2 is not required for cells to undergo senescence, but it is critical for senescent cells to evade the immune system and persist intratumorally. Indeed, after chemotherapy, PD-L2-deficient senescent cancer cells are rapidly eliminated and tumors do not produce the senescence-associated chemokines CXCL1 and CXCL2. Accordingly, PD-L2-deficient pancreatic tumors fail to recruit myeloid-derived suppressor cells and undergo regression driven by CD8 T cells after chemotherapy. Finally, antibody-mediated blockade of PD-L2 strongly synergizes with chemotherapy causing remission of mammary tumors in mice. The combination of chemotherapy with anti-PD-L2 provides a therapeutic strategy that exploits vulnerabilities arising from therapy-induced senescence. © 2024, The Author(s)

Worldwide trends in quantity and quality of published articles in the field of infectious diseases

BACKGROUND: Trying to confront with the widespread burden of infectious diseases, the society worldwide invests considerably on research. We evaluated the contribution of different world regions in research production in Infectious Diseases. METHODS: Using the online Pubmed database we retrieved articles from 38 journals included in the "Infectious Diseases" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995–2002. The world was divided into 9 regions based on geographic, economic and scientific criteria. Using an elaborate retrieval system we obtained data on published articles from different world regions. In our evaluation we introduced an estimate of both quantity and quality of research produced from each world region per year using: (1) the total number of publications, (2) the mean impact factor of publications, and (3) the product of the above two parameters. RESULTS: Data on the country of origin of the research was available for 45,232 out of 45,922 retrieved articles (98.5 %). USA and Western Europe are by far the most productive regions concerning publications of research articles. However, the rate of increase in the production of articles was higher in Eastern Europe, Africa, Latin America and the Caribbean, and Asia during the study period. The mean impact factor is highest for articles originating in the USA (3.42), while it was 2.82 for Western Europe and 2.73 for the rest of the world (7 regions combined). CONCLUSION: USA and Western Europe make up a striking 80% of the world's research production in Infectious Diseases in terms of both quantity and quality. However, all world regions achieved a gradual increase in the production of Infectious Diseases articles, with the regions ranking lower at present displaying the highest rate of increase

Sea Urchins Predation Facilitates Coral Invasion in a Marine Reserve

Macroalgae is the dominant trophic group on Mediterranean infralittoral rocky bottoms, whereas zooxanthellate corals are extremely rare. However, in recent years, the invasive coral Oculina patagonica appears to be increasing its abundance through unknown means. Here we examine the pattern of variation of this species at a marine reserve between 2002 and 2010 and contribute to the understanding of the mechanisms that allow its current increase. Because indirect interactions between species can play a relevant role in the establishment of species, a parallel assessment of the sea urchin Paracentrotus lividus, the main herbivorous invertebrate in this habitat and thus a key species, was conducted. O. patagonica has shown a 3-fold increase in abundance over the last 8 years and has become the most abundant invertebrate in the shallow waters of the marine reserve, matching some dominant erect macroalgae in abundance. High recruitment played an important role in this increasing coral abundance. The results from this study provide compelling evidence that the increase in sea urchin abundance may be one of the main drivers of the observed increase in coral abundance. Sea urchins overgraze macroalgae and create barren patches in the space-limited macroalgal community that subsequently facilitate coral recruitment. This study indicates that trophic interactions contributed to the success of an invasive coral in the Mediterranean because sea urchins grazing activity indirectly facilitated expansion of the coral. Current coral abundance at the marine reserve has ended the monopolization of algae in rocky infralittoral assemblages, an event that could greatly modify both the underwater seascape and the sources of primary production in the ecosystem