Assessment of water quality in Iran’s Anzali Wetland,using qualitative indices from 1985, 2007, and 2014

In the present study, the water quality of the Anzali Wetland, located southwest of the Caspian Sea in Iran, was compared for the years 1985, 2007, and 2014, using a weighted arithmetic mean function (National Sanitation Foundation Water Quality Index: NSFWQI_a), a weighted geometric mean function (NSFWQI_m), and the Oregon Water Quality Index (OWQI). To that end, nine water quality parameters [pH, turbidity (TURB), temperature (T), dissolved oxygen (DO), nitrate (NO₃), total solids (TS), phosphate (PO₄), biological oxygen demand (BOD₅), and fecal coliforms (FC)] were analyzed at eight selected stations. According to the proposed classification for water quality indices (higher value (0–100), better water quality), the Wetland water quality was classified as the mean values of the three indices for the three sampled years, as follows: NSFWQI_a (13.72, 12.81, 12.07); NSFWQI_m (63.049, 52.388, 49.108); and OWQI (26.867, 14.477, 15.53). The values of NSFWQI_a, NSFWQI_m, and OWQI for the western stations were better than for the other stations in the region over the 29-year span of investigation; however, the remainders of the stations’ values were very poor. Because wastewaters discharged from industrial and agricultural areas are more concentrated in the eastern part of the Anzali Wetland, the eastern stations of the Wetland showed lower water quality compared to the central and western stations. The water of the Anzali Wetland has different quality classes according to the aggregation methods employed. It is concluded that when evaluating water quality of aquatic ecosystems, several indices should be used to obtain more comprehensive results.     

Synthesis and pharmacological screening: Sulfa derivatives of 2-pipecoline-bearing 1,3,4-oxadiazole core

An electrophile, 1-(4-(bromomethylbenzenesulfonyl)-2-methylpiperidine, was synthesized by the reaction of 2-methylpiperidine (2-pipecoline) and 4-bromomethylbenzenesulfonyl chloride in a weak basic medium under pH control. A series of nucleophiles, 5-aryl/aralkyl-1,3,4-oxadiazol-2-thiols, were synthesized from corresponding carboxylic acids in three steps. The title molecules were synthesized by coupling the electrophile to nucleophiles in an aprotic medium using LiH as an activator. The structures of all synthesized compounds were corroborated through IR, ¹H NMR, and EI-MS techniques. All the compounds were screened for their pharmacological behavior, particularly, antibacterial and enzyme inhibitory activities. Notably efficient results were obtained against both gram-positive and gram-negative bacterial strains. Regarding enzyme inhibition, compounds were efficient against acetylcholinesterase and butyrylcholinesterase.     

Efficacy of different copper compounds in the control of Xanthomonas citri subsp. citri pathotypes A and A*

Citrus canker disease is one of the most devastating diseases that attacks citrus, especially limes in the Southern parts of Iran, and is caused by Xanthomonas citri subsp. citri (Xcc). The efficacy of several formulations of copper compounds including Bordeaux mixture, copper oxychloride and copper sulphate in controlling Xcc in Key lime was estimated in vitro and in planta using artificial inoculation. Specific primers were used to detect copper-resistant genes copA, copB and copL in 30 isolates of Xcc. The copA and copL genes were present in all isolates, and copB was detected only in 6 strains. In this study, we observed a very good in vitro growth inhibition activity of copper compounds against Xcc pathotype A. S14 strain (pathotype A^*) was the sole isolate that grew on media amended with 2/4 mM of Bordeaux mixture, copper oxychloride and copper sulphate. All other strains (pathotype A) failed to grow on media amended with this concentration. Bordeaux mixture exhibited high efficacy in controlling Xcc in both conditions. However, there were no significant differences in the efficacy of copper oxychloride and copper sulphate at 1.2 mM concentration in planta. A significantly minimum canker necrotic spot and highest disease control was achieved with Bordeaux mixture and copper oxychloride. There was a significant difference in disease severity of the type strain LMG9322 (pathotype A) and Xcc strain S14 (pathotype A^*). Our experiments showed that Bordeaux mixture exhibited satisfactory efficacy in controlling the causal agent of citrus canker.     

Crystal Structures of Human HMG-CoA Synthase Isoforms Provide Insights into Inherited Ketogenesis Disorders and Inhibitor Design

3-Hydroxy-3-methylglutaryl coenzyme A (CoA) synthase (HMGCS) catalyzes the condensation of acetyl-CoA and acetoacetyl-CoA into 3-hydroxy-3-methylglutaryl CoA. It is ubiquitous across the phylogenetic tree and is broadly classified into three classes. The prokaryotic isoform is essential in Gram-positive bacteria for isoprenoid synthesis via the mevalonate pathway. The eukaryotic cytosolic isoform also participates in the mevalonate pathway but its end product is cholesterol. Mammals also contain a mitochondrial isoform; its deficiency results in an inherited disorder of ketone body formation. Here, we report high-resolution crystal structures of the human cytosolic (hHMGCS1) and mitochondrial (hHMGCS2) isoforms in binary product complexes. Our data represent the first structures solved for human HMGCS and the mitochondrial isoform, allowing for the first time structural comparison among the three isoforms. This serves as a starting point for the development of isoform-specific inhibitors that have potential cholesterol-reducing and antibiotic applications. In addition, missense mutations that cause mitochondrial HMGCS deficiency have been mapped onto the hHMGCS2 structure to rationalize the structural basis for the disease pathology.     

Green synthesis of zinc nanoparticles using Lavandula angustifolia Vera. Extract by microwave method and its prophylactic effects on Toxoplasma gondii infection

BackgroundToday, a suitable vaccine has not yet been discovered to prevent Toxoplasma gondii infection. Therefore, prophylaxis can be suggested as the preferred approach to prevent toxoplasmosis. This study aims to evaluate the prophylactic effects of synthesized zinc nanoparticles (ZnNPs) using Lavandula angustifolia Vera., by microwave method on chronic toxoplasmosis in mice.MethodsBALB/c Mice orally administrated with ZnNPs the doses of 32.5, 75, 150 mg/kg/day for two weeks. On the 15th day, the mice were intraperitoneally infected with the Tehran strain of T. gondii (25 tissue cysts). The mean diameter and the numbers of brain tissue cysts, as well as the mRNA levels of inducible nitric oxide synthesize (iNOs), and interferon-gamma (IFN-γ) in mice of each experimental group were evaluated.ResultsThe synthesized ZnNPs represent a spherical form with a size ranging from 30 to 80 nm. The results revealed that oral administration of Zn NPs at the doses of 32.5 (p < 0.001) and 75 mg/kg/day (p < 0.001) for 14 days significantly reduced the mean number and diameter of the brain tissue cysts in tested mice. No T. gondii tissue cyst was observed after oral administration of Zn NPs at the doses of 150 mg/kg. Based on the results of Real-time PCR analysis, the expression level of IFN-γ and iNOs was significantly increased (p < 0.001) in mice treated with 32.5, 75, 150 mg/kg/day for two weeks.ConclusionThe obtained findings of the current investigation exhibit the significant prophylactic effects of ZnNPs against chronic toxoplasmosis in mice; so that oral administration of ZnNPs the doses 32.5, 75, 150 mg/kg reduced the parasite load and even completely controlled the infection in mice. The results show that the ZnNPs had strengthened the innate immune system which could be the reason for its strong prophylactic effects. However, further in vivo and clinical investigations are required to confirm these results as well as other possible mechanisms that can trigger these pharmacological properties.     

Selective localization of Mfn2 near PINK1 enables its preferential ubiquitination by Parkin on mitochondria

Mutations in Parkin and PINK1 cause early-onset familial Parkinson''s disease. Parkin is a RING-In-Between-RING E3 ligase that transfers ubiquitin from an E2 enzyme to a substrate in two steps: (i) thioester intermediate formation on Parkin and (ii) acyl transfer to a substrate lysine. The process is triggered by PINK1, which phosphorylates ubiquitin on damaged mitochondria, which in turn recruits and activates Parkin. This leads to the ubiquitination of outer mitochondrial membrane proteins and clearance of the organelle. While the targets of Parkin on mitochondria are known, the factors determining substrate selectivity remain unclear. To investigate this, we examined how Parkin catalyses ubiquitin transfer to substrates. We found that His433 in the RING2 domain contributes to the catalysis of acyl transfer. In cells, the mutation of His433 impairs mitophagy. In vitro ubiquitination assays with isolated mitochondria show that Mfn2 is a kinetically preferred substrate. Using proximity-ligation assays, we show that Mfn2 specifically co-localizes with PINK1 and phospho-ubiquitin (pUb) in U2OS cells upon mitochondrial depolarization. We propose a model whereby ubiquitination of Mfn2 is efficient by virtue of its localization near PINK1, which leads to the recruitment and activation of Parkin via pUb at these sites.     

Control of Blood Pressure and Risk Attenuation: Post Trial Follow-Up of Randomized Groups

Background

Evidence on long term effectiveness of public health strategies for lowering blood pressure (BP) is scarce. In the Control of Blood Pressure and Risk Attenuation (COBRA) Trial, a 2 x 2 factorial, cluster randomized controlled trial, the combined home health education (HHE) and trained general practitioner (GP) intervention delivered over 2 years was more effective than no intervention (usual care) in lowering systolic BP among adults with hypertension in urban Pakistan. However, it was not clear whether the effect would be sustained after the cessation of intervention. We conducted 7 years follow-up inclusive of 5 years of post intervention period of COBRA trial participants to assess the effectiveness of the interventions on BP during extended follow-up.

Methods

A total of 1341 individuals 40 years or older with hypertension (systolic BP 140 mm Hg or greater, diastolic BP 90 mm Hg or greater, or already receiving treatment) were followed by trained research staff masked to randomization status. BP was measured thrice with a calibrated automated device (Omron HEM-737 IntelliSense) in the sitting position after 5 minutes of rest. BP measurements were repeated after two weeks. Generalized estimating equations (GEE) were used to analyze the primary outcome of change in systolic BP from baseline to 7- year follow-up. The multivariable model was adjusted for clustering, age at baseline, sex, baseline systolic and diastolic BP, and presence of diabetes.

Findings

After 7 years of follow-up, systolic BP levels among those randomised to combined HHE plus trained GP intervention were significantly lower (2.1 [4.1–0.1] mm Hg) compared to those randomised to usual care, (P = 0.04). Participants receiving the combined intervention compared to usual care had a greater reduction in LDL-cholesterol (2.7 [4.8 to 0.6] mg/dl.

Conclusions

The benefit in systolic BP reduction observed in the original cohort assigned to the combined intervention was attenuated but still evident at 7- year follow-up. These findings highlight the potential for scaling-up simple strategies for cardiovascular risk reduction in low- and middle- income countries.

Trial Registration

ClinicalTrials.gov NCT00327574     

Food habits of the snow leopard Panthera uncia (Schreber, 1775) in Baltistan, Northern Pakistan

The snow leopard (Panthera uncia) inhabits the high, remote mountains of Pakistan from where very little information is available on prey use of this species. Our study describes the food habits of the snow leopard in the Himalayas and Karakoram mountain ranges in Baltistan, Pakistan. Ninety-five putrid snow leopard scats were collected from four sites in Baltistan. Of these, 49 scats were genetically confirmed to have originated from snow leopards. The consumed prey was identified on the basis of morphological characteristics of hairs recovered from the scats. It was found that most of the biomass consumed (70%) was due to domestic livestock viz. sheep (23%), goat (16%), cattle (10%), yak (7%), and cattle?Cyak hybrids (14%). Only 30% of the biomass was due to wild species, namely Siberian ibex (21%), markhor (7%), and birds (2%). Heavy predation on domestic livestock appeared to be the likely cause of conflict with the local inhabitants. Conservation initiatives should focus on mitigating this conflict by minimizing livestock losses.