Securing reproductive function in mungbean grown under high temperature environment with exogenous application of proline.

Escalating temperatures are adversely impacting the production potential of various cool- and warm-season crops, such as Mungbean, therefore effective strategies are required to improve heat tolerance of various crops. Mungbean, a summer season food legume, is seriously affected at temperatures more than 35/25 °C, especially at its reproductive stage, resulting in pollen infertility to induce loss of flowers and potential pods. Proline (Pro), a well-researched stress-related molecule, has been implicated in determining pollen fertility, but its involvement in affecting reproductive function under heat stress is not reported so far. In the present study, it was hypothesised that depletion of endogenous Pro in reproductive components of the flowers of heat-stressed Mungbean plants might impair the reproductive function. To test this hypothesis, Mungbean genotypes (heat tolerant and heat-sensitive), growing in outdoor environment (32.5/17.5 ±â€¯1 °C mean day/night temperature), until on the onset of flowering (30 days after sowing) were subjected to mild heat stress (MS; 40/28 °C) and high heat stress (HS; 45/33 °C), in the absence or presence of 5 mM proline treatment, applied as soil drenching and foliar spray, 2 days before imposition of heat stress. In MS plants, the endogenous Pro showed a significant increase in leaves, anthers, pollen and ovules, while in SS plants, a marked reduction was noticed. In later case, the activity of proline synthesising enzymes (pyrolline-5-carboxylate synthase and pyrroline-5-carboxylate reductase) declined severely, along with a proline catabolism enzyme (proline dehydrogenase) suggesting disruption in proline metabolism in vegetative and reproductive components. This was associated with considerable decrease in pollen germination, stigma receptivity and ovule viability in heat-stressed plants. Simultaneously, leaf tissue showed high damage to cell membranes, leaf water status, stomatal conductance and cellular respiration. Photosynthetic ability (Chlorophyll, Photo system II function), carbon fixation (RuBisCo activity) and assimilation processes (sucrose synthesis and its hydrolysis) were significantly inhibited, in heat-stressed (HS) plants, which impacted the pod number, pod and seed weight per plant. Pro treatment, especially to HS plants resulted in appreciable increase in its endogenous concentration in vegetative and reproductive parts, which significantly improved the pollen fertility as well as stigma and ovule function. At the same time, stress damage to leaves was reduced significantly, leaf water status and chlorophyll were significantly higher, as a result the carbon fixation and assimilation capacity improved notably to increase the pod set, filled pod number, pod weight and seed weight per plants, suggesting a vital role of proline in enhancing the thermo-tolerance. The effects of Pro treatment were more pronounced in heat-sensitive genotype.

Nitroimidazole carboxamides as antiparasitic agents targeting Giardia lamblia, Entamoeba histolytica and Trichomonas vaginalis.

Diarrhoeal diseases caused by the intestinal parasites Giardia lamblia and Entamoeba histolytica constitute a major global health burden. Nitroimidazoles are first-line drugs for the treatment of giardiasis and amebiasis, with metronidazole 1 being the most commonly used drug worldwide. However, treatment failures in giardiasis occur in up to 20% of cases and development of resistance to metronidazole is of concern. We have re-examined 'old' nitroimidazoles as a foundation for the systematic development of next-generation derivatives. Using this approach, derivatisation of the nitroimidazole carboxamide scaffold provided improved antiparasitic agents. Thirty-three novel nitroimidazole carboxamides were synthesised and evaluated for activity against G. lamblia and E. histolytica. Several of the new compounds exhibited potent activity against G. lamblia strains, including metronidazole-resistant strains of G. lamblia (EC50 = 0.1-2.5 µM cf. metronidazole EC50 = 6.1-18 µM). Other compounds showed improved activity against E. histolytica (EC50 = 1.7-5.1 µM cf. metronidazole EC50 = 5.0 µM), potent activity against Trichomonas vaginalis (EC50 = 0.6-1.4 µM cf. metronidazole EC50 = 0.8 µM) and moderate activity against the intestinal bacterial pathogen Clostridium difficile (0.5-2 µg/mL, cf. metronidazole = 0.5 µg/mL). The new compounds had low toxicity against mammalian kidney and liver cells (CC50 > 100 µM), and selected antiparasitic hits were assessed for human plasma protein binding and metabolic stability in liver microsomes to demonstrate their therapeutic potential.

Clinical experience with a simple algorithm for plerixafor utilization in autologous stem cell mobilization.

Plerixafor augments PBSC collection, but the optimal approach for incorporating it into mobilization is uncertain. Forty-nine consecutive patients mobilized with G-CSF alone were analyzed, and a day 4 peripheral blood CD34(+) cell count of 0.015/ml was found to predict for a day 5 apheresis yield of 2 × 10(6) CD34(+) progenitors/kg, our institutional minimum necessary for a single autologous transplant. On the basis of this relationship, a clinical guideline was developed which recommended pre-emptive use of plerixafor if the day 4 peripheral blood CD34(+) cell count was between 0.005 and 0.015/ml. A total of 166 consecutive subjects with lymphoma or plasma cell dyscrasias underwent G-CSF mobilization after adoption of this care pathway, and the mobilization failure rate was only 7% in patients managed per guideline. The median PBSC yield was 6.3 × 10(6) CD34(+) progenitors/kg with G-CSF (day 4 peripheral blood CD34(+) cell > 0.015/ml) and 4.9 × 10(6) CD34(+) progenitors/kg with G-CSF+plerixafor (day 4 peripheral blood CD34(+) cell 0.005-0.015/ml). The median number of days of apheresis was 2 in both groups. This clinical guideline is an effective mobilization algorithm that minimizes mobilization failures, reduces poor apheresis yields, does not require risk factor identification and is simple to implement.