Novel venom peptides from the cone snail Conus pulicarius discovered through next-generation sequencing of its venom duct transcriptome

ManuscriptThe venom peptides (i.e., conotoxins or conopeptides) that species in the genus Conus collectively produce are remarkably diverse, estimated to be around 50,000 to 140,000, but the pace of discovery and characterization of these peptides have been rather slow. To date, only a minor fraction have been identified and studied. However, the advent of next generation DNA sequencing technologies has opened up opportunities for expediting the exploration of this diversity. The whole transcriptome of a venom duct from the vermivorous marine snail C. pulicarius was sequenced using the 454 sequencing technology. Analysis of the data set resulted in the identification of over eighty unique putative conopeptide sequences, the highest number discovered so far from a Conus venom duct transcriptome. More importantly, majority of the sequences are potentially novel, many with unexpected structural features, hinting at the vastness of the diversity of Conus venom peptides that remains to be explored. The sequences can be classified into at least 14 major superfamilies/types (disulfide- and non-disulfide-rich), indicating the structural and functional diversity of conotoxins in the venom of C. pulicarius. In addition, the contryphans were surprisingly more diverse than what is currently known. Comparative analysis of the O-superfamily sequences also revealed insights into the complexity of the processes that drive the evolution and diversification of conotoxins

Isolation and characterization of a novel Conus peptide with apparent antinociceptive activity

Journal ArticleCone snails are tropical marine mollusks that envenomate prey with a complex mixture of neuropharmacologically active compounds. We report the discovery and biochemical characterization of a structurally unique peptide isolated from the venom of Conus marmoreus. The new peptide, mr10a, potently increased withdrawal latency in a hot plate assay (a test of analgesia) at intrathecal doses that do not produce motor impairment as measured by rotarod test

Aetiology of Depression: Insights from epidemiological and genetic research

This thesis includes several population-based studies that explore the aetiology of depression, with a specific interest on biological factors, genetics and epigenetics, and physical health factors for depression. Unravelling the aetiology of depression could potentially answer some remaining questions about depression, and finally may explain why we consistently fail to develop effective management and treatment tools for depression. Therefore, this thesis aims to apply advanced epidemiological studies and to extend the existing knowledge on the aetiology of depression. Using population- based data, the studies described in this thesis examine several risk factors and predictors that may enlighten the pathophysiological mechanism that underlie the development of depression. Specifically, Chapter 2 of this thesis presents longitudinal studies that examine the impact of potential biomarkers, such as vitamin D (Chapter 2.1), and inflammatory markers (Chapter 2.2) on the occurrence of depression. Chapter 3 of this thesis presents two studies which apply advanced genetic epidemiological methods to study the genetics of depression. Chapter 4 focuses on the epigenetics of depression and presents the largest epigenome wide association population-based study so far. Moreover, we dedicated a chapter to the impact of physical health conditions such as myocardial infarct on depression (Chapter 5.1) as well as one to the physical consequences of depression such as cognitive decline (Chapter 5.2). Finally, Chapter 6 provides a more general discussion of the main findings in this thesis and addresses several methodological considerations of the studies. Clinical implications of the results in this thesis, and future directions are also presented

Thermodynamics of Einstein-Born-Infeld black holes with negative cosmological constant

We study the thermodynamics associated to topological black hole solutions of AdS gravity coupled to nonlinear electrodynamics (Born-Infeld) in any dimension, using a background-independent regularization prescription for the Euclidean action given by boundary terms which explicitly depend on the extrinsic curvature (Kounterterms series). A finite action principle leads to the correct definition of thermodynamic variables as Noether charges, which satisfy a Smarr-like relation. In particular, for the odd-dimensional case, a consistent thermodynamic description is achieved if the internal energy of the system includes the vacuum energy for AdS spacetime.Comment: 29 pages, no figures; additional comments on extreme black hole case, a few references added; final version for PR

Report 43: Quantifying the impact of vaccine hesitancy in prolonging the need for Non-Pharmaceutical Interventions to control the COVID-19 pandemic

Vaccine hesitancy – a delay in acceptance or refusal of vaccines despite availability 1 – has the potential to threaten the successful roll-out of SARS-CoV-2 vaccines globally 2 . Here, we evaluate the potential impact of vaccine hesitancy on the control of the pandemic and the relaxation of non-pharmaceutical interventions (NPIs) by combining an epidemiological model of SARS-CoV-2 transmission 3 with data on vaccine hesitancy from population surveys. Our findings suggest that the mortality over a 2-year period could be up to 8 times higher in countries with high vaccine hesitancy compared to an ideal vaccination uptake if NPIs are relaxed. Alternatively, high vaccine hesitancy could prolong the need for NPIs to remain in place. Addressing vaccine hesitancy with behavioural interventions is therefore an important priority in the control of the COVID-19 pandemic

Geometry and stability of spinning branes in AdS gravity

The geometry of spinning codimension-two branes in AdS spacetime is analyzed in three and higher dimensions. The construction of non-extremal solutions is based on identifications in the covering of AdS space by isometries that have fixed points. The discussion focuses on the cases where the parameters of spinning states can be related to the velocity of a boosted static codimension-two brane. The resulting configuration describes a single spinning brane, or a set of intersecting branes, each one produced by an independent identification. The nature of the singularity is also examined, establishing that the AdS curvature acquires one in the form of a Dirac delta distribution. The stability of the branes is studied in the framework of Chern-Simons AdS supergravity. A class of branes, characterized by one free parameter, are shown to be stable when the BPS conditions are satisfied. In 3D, these stable branes are extremal, while in higher dimensions, the BPS branes are not the extremal ones.Comment: 40 pages, 6 figure

Presence of Listeria species in fresh meats from retail markets in Serbia

Listeria spp. are Gram positive, short, non-sporing rods, microaerophilic. Of the six species currently recognized, Listeria monocytogenes is the most important as it causes a range of infections in humans and animals. The organism can be found in a wide variety of habitats including the soil, food processing environments and raw foods. The ability of the organism to grow at refrigeration temperatures is of major importance in food production. This study examines the presence of Listeria species in fresh meat. 29 samples (chicken, pork and beef) meat. This bacteria was found in 82.7% of analyzed samples; 7 L. innocua, 8 L. monocytogenes and 9 L. welshimeri (of all isolates). L. innocua prevailed in pork meat (40%), L. monocytogenes in chicken and pork meat (30%), and L. welshimeri in beef meat (44.4%)

Optimizacija proizvodnje biodizela kukuruznog ulja metanolizom katalizovanom pepelom kurdeljke

The use of low-cost or priceless feedstocks such as byproducts in biodiesel production results in a reduced overall process costs. The present paper reports the use of corn germs and corn cobs as byproducts from corn-based starch production in the biodiesel production by the methanolysis of the oil extracted from corn germs, catalyzed by the ash produced by combustion of corn cobs. The major aim was to optimize the methanol-to-oil molar ratio, catalyst loading, and reaction time in a batch stirred reactor with respect to the content of methyl ester fatty acids (FAME). The statistical modeling and optimization were carried out using a second-order polynomial (quadratic) model developed by the response surface methodology combined with a 33 factorial design with 3 central points. The FAME content was determined by a high-pressure liquid chromatography method. The analysis of variance showed that only the catalyst amount, the reaction time, the catalyst amount interaction with reaction time and all three quadratic terms were the significant model terms with the confidence level of 95 %. The optimum reaction conditions (the catalyst amounts of 19.8 %, the methanol-to-oil molar ratio of 9.4 mol/mol and the reaction time of 31 min) provided the FAME content of 98.1 %, which was in an excellent agreement with the predicted FAME content (98.4 %). Thus, both corn germs and corn cobs may be suitable feedstocks for biodiesel production.Upotreba jeftinih ili bezvrednih sirovina, kao što su sporedni proizvodi, u proizvodnji biodizela ima za rezultat smanjene ukupne troškove procesa. U ovom radu su prikazani rezultati upotrebe kukuruznih klica i okrunjenog kukuruznog klipa (kurdeljke, krudeljke) kao sporednih proizvoda iz proizvodnje kukuruznog skroba u proizvodnji biodizela metanolizom ulja izdvojenog iz kukuruznih klica, katalizovane pepelom dobijenim sagorevanjem kurdeljke. Glavni cilj je bila optimizacija molskog odnosa metanol-ulje, količine katalizatora i reakcionog vremena u šaržnom reaktoru sa mešanjem u odnosu na sadržaj metilestra masnih kiselina (MEMK). Statističko modelovanje i optimizacija izvršeni su korišćenjem kvadratnog modela, razvijenog metodologijom odzivne površine, u kombinaciji sa 33 faktorijelnim planom sa 3 centralne tačke. Sadržaj MEMK-a je određen metodom tečne hromatografije pod visokim pritiskom. Analiza varijanse je pokazala da su samo uticaji količine katalizatora, reakcionog vremena, interakcije količine katalizatora sa reakcionim vremenom i sva tri kvadratna člana statistički značajni sa nivoom pouzdanosti od 95 %. Pod optimalnim reakcionim uslovima (količina katalizatora 19,8 %, molski odnos metanol/ulje 9,4 mol/mol i reakciono vreme 31 min) dobijen je sadržaj MEMK-a od 98,1 %, koji se slaže sa predviđenim sadržajem MEMK-a (98,4 %). Prema tome, i kukuruzne klice i kurdeljka mogu biti pogodne sirovine za proizvodnju biodizela

Turrids in the Outer Barrier Reef, Northeast Bohol, Philippines from Lumun-Lumun Nets

The micro turrids in the sandy sediments substrata of Outer Barrier Reef, Danajon Bank were systematically investigated using two different methodologies: sediment suction and \emph{lumun-lumun} nets. Turrids morphospecies recovered from the experimental \emph{lumun-lumun} nets, which are a bundle of fine mesh fishing nets set at 15 m depth in the subtidal sandy sediments of outer barrier reef for two months during intermonsoon, southwest monsoon and northeast monsoon seasons were analyzed. The sediments suction method was also used to collect micro turrids in the sandy sediment substrata in the Outer Barrier Reef. Results of the analysis revealed that the turrids collected at 3m and 15m depth representing natural habitat sandy substrate had about $30\%$ morphospecies similar. The composition of turrids morphospecies collected from the natural habitat sandy substrate and in the \emph{lumun-lumun} nets were different with only one species shared by the two methods of collecting micromollusks probably due to nocturnal behavior of turrids which could have smaller chances of collecting during day time. However, \emph{lumun-lumun} nets are efficient in colonizing the free-swimming veliger and may serve as better sampler in collecting turrid recruits. The recovery of $80\%$ microturrids in the net proved that \emph{lumun-lumun} is efficient in recovering live tiny gastropods than the conventional sediment suctioning method; providing great opportunity for anatomical, morphological and molecular analysis. The very low overlap of turrid morphospecies obtained in the \emph{lumun-lumun} nets across monsoon periods implies that turrids are not self-seeding gastropod