Interspecific variation, habitat complexity and ovipositional responses modulate the efficacy of cyclopoid copepods in disease vector control

The use of predatory biological control agents can form an effective component in the management of vectors of parasitic diseases and arboviruses. However, we require predictive methods to assess the efficacies of potential biocontrol agents under relevant environmental contexts. Here, we applied functional responses (FRs) and reproductive effort as a proxy of numerical responses (NRs) to compare the Relative Control Potential (RCP) of three cyclopoid copepods, Macrocyclops albidus, M. fuscus and Megacyclops viridis towards larvae of the mosquito Culex quinquefasciatus. The effects of habitat complexity on such predatory impacts were examined, as well as ovipositional responses of C. quinquefasciatus to copepod cues in pairwise choice tests. All three copepod species demonstrated a population destabilising Type II FR. M. albidus demonstrated the shortest handling time and highest maximum feeding rate, whilst M. fuscus exhibited the highest attack rate. The integration of reproductive effort estimations in the new RCP metric identifies M. albidus as a very promising biocontrol agent. Habitat complexity did not impact the FR form or maximum feeding rate of M. albidus, indicating that potentially population destabilising effects are robust to habitat variations; however, attack rates of M. albidus were reduced in the presence of such complexity. C. quinquefasciatus avoided ovipositing where M. albidus was physically present, however it did not avoid chemical cues alone. C. quinquefasciatus continued to avoid M. albidus during oviposition when both the treatment and control water were dyed; however, when an undyed, predator-free control was paired with dyed, predator-treated water, positive selectivity towards the treatment water was stimulated. We thus demonstrate the marked predatory potential of cyclopoid copepods, utilising our new RCP metric, and advocate their feasibility in biological control programmes targeting container-style habitats. We also show that behavioural responses of target organisms and environmental context should be considered to maximise agent efficacy

Mutation of the Zebrafish Nucleoporin elys Sensitizes Tissue Progenitors to Replication Stress

The recessive lethal mutation flotte lotte (flo) disrupts development of the zebrafish digestive system and other tissues. We show that flo encodes the ortholog of Mel-28/Elys, a highly conserved gene that has been shown to be required for nuclear integrity in worms and nuclear pore complex (NPC) assembly in amphibian and mammalian cells. Maternal elys expression sustains zebrafish flo mutants to larval stages when cells in proliferative tissues that lack nuclear pores undergo cell cycle arrest and apoptosis. p53 mutation rescues apoptosis in the flo retina and optic tectum, but not in the intestine, where the checkpoint kinase Chk2 is activated. Chk2 inhibition and replication stress induced by DNA synthesis inhibitors were lethal to flo larvae. By contrast, flo mutants were not sensitized to agents that cause DNA double strand breaks, thus showing that loss of Elys disrupts responses to selected replication inhibitors. Elys binds Mcm2-7 complexes derived from Xenopus egg extracts. Mutation of elys reduced chromatin binding of Mcm2, but not binding of Mcm3 or Mcm4 in the flo intestine. These in vivo data indicate a role for Elys in Mcm2-chromatin interactions. Furthermore, they support a recently proposed model in which replication origins licensed by excess Mcm2-7 are required for the survival of human cells exposed to replication stress

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Biocidal and inhibitive duality of naturally occurring substance azadiracta indica on mild steel in fresh water

This paper deals with the biocidal and inhibitive effects of aqueous extract of Azardiracta indica (neem) on mild steel in fresh water environment. The extract retards the corrosive effect to an extent, which mainly depends on the concentration and stability of the extract. The biocidal and inhibitive properties are investigated by pour plate technique and by weight loss measurements, potentiodynamic polarization and AC impedance measurements. The inhibition activity is due to the adsorption of natural compounds, which are found in A.indica extrac