A conserved guided entry of tail-anchored pathway is involved in the trafficking of a subset of membrane proteins in Plasmodium falciparum.

Tail-anchored (TA) proteins are defined by the absence of N-terminus signal sequence and the presence of a single transmembrane domain (TMD) proximal to their C-terminus. They play fundamental roles in cellular processes including vesicular trafficking, protein translocation and quality control. Some of the TA proteins are post-translationally integrated by the Guided Entry of TA (GET) pathway to the cellular membranes; with their N-terminus oriented towards the cytosol and C-terminus facing the organellar lumen. The TA repertoire and the GET machinery have been extensively characterized in the yeast and mammalian systems, however, they remain elusive in the human malaria parasite Plasmodium falciparum. In this study, we bioinformatically predicted a total of 63 TA proteins in the P. falciparum proteome and revealed the association of a subset with the P. falciparum homolog of Get3 (PfGet3). In addition, our proximity labelling studies either definitively identified or shortlisted the other eligible GET constituents, and our in vitro association studies validated associations between PfGet3 and the corresponding homologs of Get4 and Get2 in P. falciparum. Collectively, this study reveals the presence of proteins with hallmark TA signatures and the involvement of evolutionary conserved GET trafficking pathway for their targeted delivery within the parasite.

Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum.

BACKGROUND: Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment. METHODS: The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-ß-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library. RESULTS: Among all the compounds screened, 1-aryltetrahydro-ß-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds. CONCLUSION: Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum.

Efficacy of spent tea waste as chemically impregnated adsorbent involving ortho-phosphoric and sulphuric acid for abatement of aqueous phenol-isotherm, kinetics and artificial neural network modelling.

The current study emphasises on sorptive expulsion of phenol from aqueous solution using ortho-phosphoric acid (STAC-O) and sulphuric acid (STAC-H)-activated biochar derived from spent tea waste. STAC-O and STAC-H were instrumentally anatomised using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), BET surface area and thermal gravimetric analyser. Equilibrium and kinetic data were implemented for the investigative parametric batch study to prospect the influence of adsorbent dosage, contact time, initial concentration and pH for eradication of phenol from aqueous solution. The maximum phenolic removals by STAC-O and STAC-H are 93.59% and 91.024% respectively at the parametric conditions of adsorbent dosage 3 g/l time 2 h, initial phenol concentration 100 mg/l and pH 8. Non-linear regression of adsorption isotherms and kinetics was accomplished using the equilibrium data. Both the specimens were compared, and it delineated that Temkin isotherm model is contented. The maximum adsorption intakes for STAC-H and STAC-O were 185.002 mg/g and 154.39 mg/g respectively. Pseudo-second-order kinetic model was best fitted for portraying the chemisorption phenomena. Boyd kinetic and intra-particle diffusion model were investigated to elucidate the diffusion mechanism involved in the process. Desorption study was employed for determining the regeneration proficiency of the adsorbents using water, ethanol and NaOH with maximum 93% and 51.16% extrusion for STAC-O and STAC-H respectively. The process parameters involved in this study were further analysed using artificial neural network perusal to determine the input-output relationships and data pattern. The overall adsorption study along with cost estimation exhibited that bidirectional activation of spent tea biochar was prospective in abatement of phenol from aqueous media.

Maturation profile and fecundity of the exotic Oreochromis niloticus in the River Yamuna, India.

The knowledge on the reproductive biology of fish Oreochromis niloticus (Linnaeus, 1758) in riverine condition is meagre in the Indian sub-continent which is necessary for the development of an appropriate fishery management protocols for the rivers. In this context, the gonadal maturation profile and fecundity of 0. niloticus was studied. Mature, spawning and spent females recorded in almost all the months of the year evidenced multiple and prolonged breeding behaviour. An overall sex ratio (M/F) of 1: 1.08 observed was statistically non-significant from expected 1:1 ratio (chi2=6.994219, p=0.8642) indicating that males and females were statistically equal in number. The absolute fecundity ranged from 1192 to 4760 with mean of 2590 eggs from ovary weighing between 1.91 g to 28.89 g. Monthly changes in gonado-somatic index (GSI) revealed that fish bred throughout the year except in July and August, but at peak between October-November and March-June. Size at first maturity of male was estimated as 229.6 mm with confidence limit of 235.9 and 223.6 mm and for female as 238.1 mm with confidence limit of 244.7 and 231.7 mm, respectively.