Structural basis for feedforward control in the PINK1/Parkin pathway

PINK1 and parkin constitute a mitochondrial quality control system mutated in Parkinson’s disease. PINK1, a kinase, phosphorylates ubiquitin to recruit parkin, an E3 ubiquitin ligase, to mitochondria. PINK1 controls both parkin localization and activity through phosphorylation of both ubiquitin and the ubiquitin‐like (Ubl) domain of parkin. Here, we observed that phospho‐ubiquitin can bind to two distinct sites on parkin, a high‐affinity site on RING1 that controls parkin localization and a low‐affinity site on RING0 that releases parkin autoinhibition. Surprisingly, ubiquitin vinyl sulfone assays, ITC, and NMR titrations showed that the RING0 site has higher affinity for phospho‐ubiquitin than phosphorylated Ubl in trans. We observed parkin activation by micromolar concentrations of tetra‐phospho‐ubiquitin chains that mimic mitochondria bearing multiple phosphorylated ubiquitins. A chimeric form of parkin with the Ubl domain replaced by ubiquitin was readily activated by PINK1 phosphorylation. In all cases, mutation of the binding site on RING0 abolished parkin activation. The feedforward mechanism of parkin activation confers robustness and rapidity to the PINK1‐parkin pathway and likely represents an intermediate step in its evolutionary development.     

Runoff and drainage water quality from geotextile and gravel pads used in livestock feeding and loafing areas

Geotextile and gravel pads offer a low-cost alternative to concrete for providing all-weather surfaces for cattle and vehicle traffic, and are used in many livestock facilities to minimize mud, runoff and erosion of heavy traffic areas. The objective of this study was to compare different combinations of geotextile and gravel used in heavy livestock traffic areas that minimize the potential for water pollution. Three different pad combinations were constructed in 2.4 x 6-m plots as follows: (i) woven geotextile+100mm of gravel+50mm Dense Grade Aggregate (DGA); (ii) woven geotextile + geoweb+100 mm DGA; and (iii) non-woven geotextile+152 mm of gravel+50mm DGA; (iv) mud lots as control. The third combination was equivalent to one of the base treatments specified by the Kentucky Natural Resource and Conservation Service (NRCS). All treatment combinations were duplicated. Lysimeter pans were installed in four out of eight plots for the collection of leachate or drainage water. Runoff was collected at the lower end of the plots. About 14 kg of beef cattle manure were added evenly to the plots. Rainfall at 50mm/h was applied using rainfall simulators. In the first five of ten experiments, manure was removed from the surface of the pads after each experiment. In the remaining five experiments manure accumulated on the surface of the pads. The effect of pad treatment was significant on the electrical conductivity (EC), total solids (TS), chemical oxygen demand (COD), nitrite (NO2-N), total nitrogen (TN) and total phosphorus (TP) values in surface runoff at the 5% level. Manure removal did not have any significant effect on the nutrient content of runoff or leachate samples except for ammonia (NH4-N) values. Although a mass balance indicated relatively small amounts of organic matter and nutrients were lost by runoff and leaching, the actual contamination level of both runoff and leachate samples were high; TP levels as high as 12 mg/l (5.4 mg/m2) in runoff and nitrate (NO3-N) values as high as 10.8 mg/l (1.6 mg/m2) in leachate were observed.     

Place prioritization for biodiversity conservation using probabilistic surrogate distribution data

We analyse optimal and heuristic place prioritization algorithms for biodiversity conservation area network design which can use probabilistic data on the distribution of surrogates for biodiversity. We show how an Expected Surrogate Set Covering Problem (ESSCP) and a Maximal Expected Surrogate Covering Problem (MESCP) can be linearized for computationally efficient solution. For the ESSCP, we study the performance of two optimization software packages (XPRESS and CPLEX) and five heuristic algorithms based on traditional measures of complementarity and rarity as well as the Shannon and Simpson indices of α‐diversity which are being used in this context for the first time. On small artificial data sets the optimal place prioritization algorithms often produced more economical solutions than the heuristic algorithms, though not always ones guaranteed to be optimal. However, with large data sets, the optimal algorithms often required long computation times and produced no better results than heuristic ones. Thus there is generally little reason to prefer optimal to heuristic algorithms with probabilistic data sets.     

A short note on predicted motifs in the Thaparocleidus wallagonius genome

Thaparocleidus wallagonius is a monogenean parasite and a fish-borne pathogen with a worldwide distribution. The genome for Thaparocleidus wallagonius is known. Therefore, it is of interest to report the DNA motif analysis data in the 18S rDNA of Thaparocleidus wallagonius collected from the fish Wallago attu in India. This data forms a framework for an in-depth analysis of the parasite biology and development, immune evasion strategies, virulence and long-term survival within the definitive host.     

An unusual presentation of filariasis: a case report

BACKGROUND: Filariasis and its consequences are a major health problem in tropical countries, including the Indian subcontinent. Despite its high incidence, it is unusual to find microfilaria in fine needle aspiration cytology (FNAC) smears. We present a case of subcutaneous firm to cystic swelling, aspiration of which revealed a large number of microfilaria. CASE: A 30-year-old man presented with a chain of intermittent, firm swellings in both arms. FNAC of the swellings revealed a large number of 4 microfilariae with associated giant cell reaction and inflammatory cell-like eosinophils. CONCLUSION: Besides the documented usual mode of presentation of filarial infection, it can present in an atypical manner, so careful examination of aspirates from the subcutaneous swellings, especially in filariasis endemic zones, is very important.     

Microwave enhanced solid support synthesis of fluorine containing benzopyrano-triazolo-thiadiazepines as potent anti-fungal agents

A facile, dry media procedure has been developed for the synthesis of a series of a new class of fluorine containing 3-alkyl-7-chloro-11a,12-dihydro-11-phenyl-12-(substituted aryl)-11H-benzopyrano[4,3-e][1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazepines (4a-k) under microwaves using basic alumina as solid support. The reaction time has been brought down from hours (60-65 h) to minutes (3-5 min) with improved yield as compared to conventional method, demonstrating the versatility of the process. The method reported herein is devoid of the hazards of solution-phase reactions. The synthesized compounds have been screened 'in vitro' for anti-fungal activity against Rhizoctonia solani, Fusarium oxysporum and Collectotrichum capsici. Most of the compounds have shown good activity against these pathogens.