Integrated mapping of establishment risk for emerging vector-borne infections: a case study of canine leishmaniasis in southwest France

Background

Zoonotic visceral leishmaniasis is endemic in the Mediterranean Basin, where the dog is the main reservoir host. The disease''s causative agent, Leishmania infantum, is transmitted by blood-feeding female sandflies. This paper reports an integrative study of canine leishmaniasis in a region of France spanning the southwest Massif Central and the northeast Pyrenees, where the vectors are the sandflies Phlebotomus ariasi and P. perniciosus.

Methods

Sandflies were sampled in 2005 using sticky traps placed uniformly over an area of approximately 100 by 150 km. High- and low-resolution satellite data for the area were combined to construct a model of the sandfly data, which was then used to predict sandfly abundance throughout the area on a pixel by pixel basis (resolution of c. 1 km). Using literature- and expert-derived estimates of other variables and parameters, a spatially explicit R ₀ map for leishmaniasis was constructed within a Geographical Information System. R ₀ is a measure of the risk of establishment of a disease in an area, and it also correlates with the amount of control needed to stop transmission.

Conclusions

To our knowledge, this is the first analysis that combines a vector abundance prediction model, based on remotely-sensed variables measured at different levels of spatial resolution, with a fully mechanistic process-based temperature-dependent R ₀ model. The resulting maps should be considered as proofs-of-principle rather than as ready-to-use risk maps, since validation is currently not possible. The described approach, based on integrating several modeling methods, provides a useful new set of tools for the study of the risk of outbreaks of vector-borne diseases.     

Putting your eggs in several baskets: oviposition in a wasp that walks between several figs

The interaction between figs (Ficus spp., Moraceae) and their pollinator fig wasps (Hymenoptera: Agaonidae) is an obligate mutualism, but females of dioecious fig trees exploit fig wasps without providing rewards. Figs are closed inflorescences that typically trap pollinator females after entry, but some fig wasp species can re‐emerge (although wingless) and subsequently oviposit in and pollinate further figs. Using glasshouse populations, we examined the sex ratios and clutches laid by single foundresses of Kradibia tentacularis (Grandi) in their first and subsequent male figs of Ficus montana Blume, and how the probability of emergence and entering a second fig varied between seasons. A maximum of four figs were entered by any one foundress. Wingless foundresses were able to locate and enter figs up to 60 cm from the first fig they entered, but the probability of entry declined sharply with distance from that fig. The foundresses that re‐emerged produced slightly higher adult offspring totals than those that failed to re‐emerge. Clutch sizes of a single foundress in its first fig equalled those in all the subsequent figs combined, with clutch size per fig decreasing when more figs were entered. Smaller clutches had less female‐biased sex ratios. Figs were more numerous in summer than in winter, but the proportion of figs entered by only wingless foundresses remained unchanged. Movement between figs increases pollinator reproductive success in male figs, thereby encouraging foundresses that encounter a female tree to also move between and pollinate several female figs.     

Molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein

The MUC1 oncoprotein is known to be linked with different types of cancer. Therefore, it is of interest to document the molecular docking analysis of compounds from Justica adhatoda L with the MUC1 oncoprotein. We report the structure based molecular binding features compounds such as amrinone, ethambutol, pyrazinamide and vasicoline the MUC1 oncoprotein for further consideration in drug discovery.     

Performance of suspended and attached growth MBR systems in treating high strength synthetic wastewater

The performance of laboratory-scale attached growth (AG) and suspended growth (SG) membrane bioreactors (MBRs) was evaluated in treating synthetic wastewater simulating high strength domestic wastewater. This study investigated the influence of sponge suspended carriers in AG-MBR system, occupying 15% reactor volume, on the removal of chemical oxygen demand (COD), total nitrogen (TN) and total phosphorus (TP), and compared it to that of SG-MBR. Results showed that the removal efficiencies of COD, TN and TP in AG-MBR were 98%, 89% and 58%, respectively as compared to 98%, 74% and 38%, respectively in SG-MBR. Improved TN removal in AG-MBR systems was primarily based on simultaneous nitrification and denitrification (SND) process. These results infer that the presence of small bio-particles having higher microbial activity and the growth of complex biomass captured within the suspended sponge carriers resulted in improved TN and TP removal in AG-MBR.     

Kinetic study of partially purified cellulase enzyme produced by Trichoderma viride FCBP-142 and its hyperactive mutants

Cellulases are the enzymes that cleave beta-1,4 linkages of cellulose, and carbohydrate that is main part of plants' cell walls. Presently, cellulase isolation and partial purification was executed through ammonium sulfate precipitation. The isolated protein of parental and derived mutants conferred molecular weights of 30, 45 and 55 kDa. The optimum temperature for maximal cellulase activity was 50 degrees C with Ea for substrate hydrolysis of 77.73, 83.97 and 83.14 kJ mol(-1) and temperature quotient of 1.0020, 1.0022 and 1.0022 by Trichoderma viride FCBP-142, Tv-UV-5.6 and Tv-Ch-4.3, respectively. The enzyme was stable at 50 degrees C for about 60 min but rapid denaturation occurred above 55 degrees C. The enzyme showed optimum activity at pH 4.0 and involved two types of acidic and basic limbs with pKa1 and pKa2. The pKa1 of active site presented a significant shift from 2.55 to 2.9 and 3.1 by Tv-UV-5.6 and Tv-Ch-4.3, respectively in comparison to parental strain. Likewise, pKa2 moved from 6.05 to 6.5 and 6.4. Enzyme kinetics displayed Michaelis-Menten constant Km 0.6, 0.5 and 0.28 mg mL(-1) and Vmax value of 8.33, 10 and 9.09 Units mL(-1) for parental, Tv-UV-5.6 and Tv-Ch-4.3, respectively.     

Antidepressant-like deliverables from the sea: evidence on the efficacy of three different brown seaweeds via involvement of monoaminergic system

Brown seaweeds exhibit several health benefits in treating and managing wide array of ailments. In this study, the antidepressant-like effect of methaolic extracts from Sargassum swartzii (SS), Stoechospermum marginatum (SM), and Nizamuddinia zanardinii (NZ) was examined in forced swimming test (FST), in rats. Oral administration of SS, SM, and NZ extract (30–60 mg/kg) exhibited antidepressant-like activity in FST by reducing immobility time as compared to control group, without inducing significant change in ambulatory behavior in open field test. In order to evaluate the involvement of monoaminergic system, rats were pretreated with the inhibitor of brain serotonin stores p-chlorophenylalanin (PCPA), dopamine (SCH23390 and sulpiride), and adrenoceptor (prazosin and propranolol) antagonists. Rats receiving treatment for 28 days were decapitated and brains were analyzed for monoamine levels. It may be concluded that the extracts of SS, SM, and NZ produces antidepressant-like activity via modulation of brain monoaminergic system in a rat model.     

Identification of the Site of Inhibition of Oncogenic ras–p21-Induced Signal Transduction by a Peptide from a ras Effector Domain

We have previously found that a peptide corresponding to residues 35–47 of the ras-p21 protein, from its switch 1 effector domain region, strongly inhibits oocyte maturation induced by oncogenic p21, but not by insulin-activated cellular wild-type p21. Another ras–p21 peptide corresponding to residues 96–110 that blocks ras–jun and jun kinase (JNK) interactions exhibits a similar pattern of inhibition. We have also found that c-raf strongly induces oocyte maturation and that dominant negative c-raf strongly blocks oncogenic p21-induced oocyte maturation. We now find that the p21 35–47, but not the 96–110, peptide completely blocks c-raf-induced maturation. This finding suggests that the 35–47 peptide blocks oncogenic ras at the level of raf; that activated normal and oncogenic ras–p21 have differing requirements for raf-dependent signaling; and that the two oncogenic-ras-selective inhibitory peptides, 35–47 and 96–110, act at two different critical downstream sites, the former at raf, the latter at JNK/jun, both of which are required for oncogenic ras-p21 signaling.     

Inflammation and serotonin deficiency in major depressive disorder: molecular docking of antidepressant and anti-inflammatory drugs to tryptophan and indoleamine 2,3-dioxygenases

The roles of the kynurenine pathway (KP) of tryptophan (Trp) degradation in serotonin deficiency in major depressive disorder (MDD) and the associated inflammatory state are considered in the present study. Using molecular docking in silico, we demonstrate binding of antidepressants to the crystal structure of tryptophan 2,3-dioxygenase (TDO) but not to indoleamine 2,3-dioxygenase (IDO). TDO is inhibited by a wide range of antidepressant drugs. The rapidly acting antidepressant ketamine does not dock to either enzyme but may act by inhibiting kynurenine monooxygenase thereby antagonising glutamatergic activation to normalise serotonin function. Antidepressants with anti-inflammatory properties are unlikely to act by direct inhibition of IDO but may inhibit IDO induction by lowering levels of proinflammatory cytokines in immune-activated patients. Of six anti-inflammatory drugs tested, only salicylate docks strongly to TDO and apart from celecoxib, the other five dock to IDO. TDO inhibition remains the major common property of antidepressants and TDO induction the most likely mechanism of defective serotonin synthesis in MDD. TDO inhibition and increased free Trp availability by salicylate may underpin the antidepressant effect of aspirin and distinguish it from other nonsteroidal anti-inflammatory drugs. The controversial findings with IDO in MDD patients with an inflammatory state can be explained by IDO induction being overridden by changes in subsequent KP enzymes influencing glutamatergic function. The pathophysiology of MDD may be underpinned by the interaction of serotonergic and glutamatergic activities.     

Biallelic variants in TRAPPC10 cause a microcephalic TRAPPopathy disorder in humans and mice

The highly evolutionarily conserved transport protein particle (TRAPP) complexes (TRAPP II and III) perform fundamental roles in subcellular trafficking pathways. Here we identified biallelic variants in TRAPPC10, a component of the TRAPP II complex, in individuals with a severe microcephalic neurodevelopmental disorder. Molecular studies revealed a weakened interaction between mutant TRAPPC10 and its putative adaptor protein TRAPPC2L. Studies of patient lymphoblastoid cells revealed an absence of TRAPPC10 alongside a concomitant absence of TRAPPC9, another key TRAPP II complex component associated with a clinically overlapping neurodevelopmental disorder. The TRAPPC9/10 reduction phenotype was recapitulated in TRAPPC10^-/- knockout cells, which also displayed a membrane trafficking defect. Notably, both the reduction in TRAPPC9 levels and the trafficking defect in these cells could be rescued by wild type but not mutant TRAPPC10 gene constructs. Moreover, studies of Trappc10^-/- knockout mice revealed neuroanatomical brain defects and microcephaly, paralleling findings seen in the human condition as well as in a Trappc9^-/- mouse model. Together these studies confirm autosomal recessive TRAPPC10 variants as a cause of human disease and define TRAPP-mediated pathomolecular outcomes of importance to TRAPPC9 and TRAPPC10 mediated neurodevelopmental disorders in humans and mice.     

Physiological responses of wheat to drought stress and its mitigation approaches

Drought is a polygenically controlled stress and a major agricultural risk that reduces crop productivity and limits the successful insight of land potential throughout the world. This review article has been divided into two parts, i.e., effect of drought stress on physiology of wheat and potential drought mitigation approaches. In the first part, physiological responses of wheat to stress were discussed. Cell membrane stability, relative water content, early maturity, decreased leaf area, small plant size, increased dry weight and root–shoot ratio, and the whole-plant transpiration rate response to enhanced atmospheric vapor pressure deficit are physiological traits associated with drought tolerance in wheat. Reduction of relative water content closes stomata and thereby reduces stomatal conductance. Osmotic adjustment improves drought tolerance by allowing cell enlargement, plant growth, and stomata to stay partially open and by maintaining CO₂ fixation under severe water deficit. The wheat plant accumulates several organic and inorganic solutes in its cytosol to lessen its osmotic potential for maintenance of cell turgor. Drought affects photosynthesis negatively by changing the inner structure of chloroplasts, mitochondria, and chlorophyll content and minerals. Destruction of the photosystem II (PSII) oxygen releasing complex and reaction center can disturb production and use of electrons, causing lipid peroxidation of cell membrane through the production of reactive oxygen species. In the second part, drought mitigation approaches were discussed. Seed, drought, bacterial, and hormonal priming are common approaches used to lessen the effects of water deficit. Physiological trait-based breeding, molecular breeding, marker-assisted backcrossing, aerial phenotyping, water budgeting, and resource allocation are modern approaches used to develop drought tolerant wheat cultivars. Wheat genotypes produced as a result of a combination of all these methodologies will increase food security regarding the currently changing climate.