Study of Various Pyridazine and Phthalazine Drugs with Diverse Therapeutical and Agrochemical Activities

Russian Journal of Bioorganic Chemistry - Pyridazines hold considerable interest relative to pharmacologically active molecules. The pyridazine compounds are exhibited different types of...     

Fine-scale spatial distribution of soil organic carbon and its fractions after afforestation with Pinus sylvestris and Salix psammophila in a semiarid desert of China

半干旱沙漠中樟子松和沙柳造林后土壤有机碳及其组分的小尺度空间分布 半干旱沙漠造林有助于改善土壤功能以及增加土壤有机碳(SOC)固定,但人们对造林后SOC及其不稳定(LOC)组分的小尺度空间分布了解甚少。本研究以毛乌素沙地东南缘樟子松(Pinus sylvestris)和沙柳 (Salix psammophila)为研究对象,量化了距离树体20、80、150和240 cm处SOC、LOC组分及其相关变量的小尺度空间分布。研究结果表明,沙柳和樟子松造林显著提高了SOC、总氮(TN)、可溶性有机碳 (DOC)、微生物碳(MBC)和易氧化有机碳(ROOC)含量;在距离树体20 cm处,0–100 cm土层樟子松SOC 储量比沙柳高27.21%;在距离树体80和150 cm处,沙柳SOC储量分别比樟子松高5.50%和5.66%;与流 沙地相比,在距离树体20、80、150 和240 cm处,沙柳和樟子松SOC储量显著增加了94.90%、39.50%、 27.10%和18.50%;沙柳和樟子松ROOC分别占SOC的14.09%和18.93%。总之,造林促进了半干旱流沙地SOC的积累,樟子松比沙柳分配更多的有机质到距离树体<80 cm范围内的土体中。     

Novel mutation G324C in <Emphasis Type="Italic">WNT1</Emphasis> mapped in a large Pakistani family with severe recessively inherited <Emphasis Type="Italic">Osteogenesis Imperfecta</Emphasis>

Introduction

Osteogenesis imperfecta (OI) is a clinically and genetically heterogeneous disease with skeletal fragility and variable extra-skeletal manifestations. To date several point mutations in 18 different genes causing different types of OI have been identified. Mutations in WNT1 compromise activity of the osteoblasts leading to disturbed bone mass accrual, fragility fractures and progressive skeletal abnormalities. The present study was conducted to determine the underlying genetic cause of an autosomal recessive skeletal dysplasia in a large consanguineous family from Chinute, Pakistan.

Materials and methods

Blood was collected from 24 individuals of affected family along with clinical data. Homozygosity mapping was performed to confirm consanguinity. SNPs were identified, followed by whole exome and Sanger sequencing. In silico characterization of WNT1 mutation was performed using multiple platforms.

Results

Nine affected family members exhibited severe bone deformities, recurrent fractures, short stature and low bone mineral density. SNP array data revealed homozygous segments >?1 Mb in length accounting for 2.1–12.7% of the genome in affected individuals and their siblings and a single 6,344,821 bp homozygous region in all affected individuals on chromosome 12q12-q13. This region includes two potential OI candidate genes WNT1 and VDR. We did whole-exome sequencing for both genes in two patients and identified a novel damaging missense mutation in exon 4 of WNT1: c.1168G?>?T (NM_005430) resulting in p.G324C. Sanger sequencing confirmed segregation of mutation with the disease in family.

Conclusion

We report a novel mutation responsible for OI and our investigation expands the spectrum of disease-causing WNT1 mutations and the resulting OI phenotypes.

     

Metabolic Syndrome Is Associated with Increased Oxo-Nitrative Stress and Asthma-Like Changes in Lungs

Epidemiological studies have shown an increased obesity-related risk of asthma. In support, obese mice develop airway hyperresponsiveness (AHR). However, it remains unclear whether the increased risk is a consequence of obesity, adipogenic diet, or the metabolic syndrome (MetS). Altered L-arginine and nitric oxide (NO) metabolism is a common feature between asthma and metabolic syndrome that appears independent of body mass. Increased asthma risk resulting from such metabolic changes would have important consequences in global health. Since high-sugar diets can induce MetS, without necessarily causing obesity, studies of their effect on arginine/NO metabolism and airway function could clarify this aspect. We investigated whether normal-weight mice with MetS, due to high-fructose diet, had dysfunctional arginine/NO metabolism and features of asthma. Mice were fed chow-diet, high-fat-diet, or high-fructose-diet for 18 weeks. Only the high-fat-diet group developed obesity or adiposity. Hyperinsulinemia, hyperglycaemia, and hyperlipidaemia were common to both high-fat-diet and high-fructose-diet groups and the high-fructose-diet group additionally developed hypertension. At 18 weeks, airway hyperresponsiveness (AHR) could be seen in obese high-fat-diet mice as well as non-obese high-fructose-diet mice, when compared to standard chow-diet mice. No inflammatory cell infiltrate or goblet cell metaplasia was seen in either high-fat-diet or high-fructose-diet mice. Exhaled NO was reduced in both these groups. This reduction in exhaled NO correlated with reduced arginine bioavailability in lungs. In summary, mice with normal weight but metabolic obesity show reduced arginine bioavailability, reduced NO production, and asthma-like features. Reduced NO related bronchodilation and increased oxo-nitrosative stress may contribute to the pathogenesis.     

Bacteriostatic stimulus of meropenem on allelochemical-metabolizing Burkholderia sp. LS-044 mitigates ferulic acid autotoxicity in rice (Oryza sativa ssp. japonica cv. Tainung 71)

Plant and Soil - To screen plant-associated Burkholderia strains for plant probiotic traits including allelochemical metabolism and understand their role on rice allelopathy using a...     

Novel 2,4-dichlorophenoxy acetic acid substituted thiazolidin-4-ones as anti-inflammatory agents: Design,synthesis and biological screening

A library of fourteen 2-imino-4-thiazolidinone derivatives (1a-1n) has been synthesized and evaluated for in vivo anti-inflammatory activity and effect on ex-vivo COX-2 and TNF–α expression. Compounds 1k (5-(2,4-dichloro-phenooxy)-acetic acid (3-benzyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) and 1m (5-(2,4-dichloro-phenooxy)-acetic acid (3-cyclohexyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) exhibited in vivo inhibition of 81.14% and 78.80% respectively after 5 h in comparison to indomethacin which showed 76.36% inhibition of inflammation without causing any damage to the stomach. Compound 1k showed a reduction of 68.32% in the level of COX-2 as compared to the indomethacin which exhibited 66.23% inhibition of COX-2. The selectivity index of compound 1k was found to be 29.00 in comparison to indomethacin showing selectivity index of 0.476. Compounds 1k and 1m were also found to significantly suppress TNF-α concentration to 70.10% and 68.43% in comparison to indomethacin which exhibited 66.45% suppression.     

Sunflower germination and growth behavior under various gamma radiation absorbed doses

Gamma radiation, various absorbed doses (0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5 krad) effects were evaluated on sunflower (Helianthus annus. L.) germination and growth characteristics. Sunflower healthy seeds were exposed to gamma radiation source Co⁶⁰ at nuclear institute for food and agriculture and exposed seeds were grown under controlled laboratory conditions. In comparison to control, gamma radiation absorbed doses affected the measured response positively i.e., radical length, plumule length, number of roots, seedling fresh weight, seedling dry weight, germination percentage, time of germination and diameter of hypocotyl of sunflower enhanced up to 83.15%, 70.32%, 73.03%, 4.80%, 3.26%, 72.0%, ? 18.88% and 12.58%, respectively. The time of germination, fresh weight and percent moisture contents enhanced insignificantly, however, the response was higher than control. All gamma radiation absorbed doses showed a stimulatory effect on sunflower germination and seedling growth characteristics. The low gamma radiation absorbed doses were found to be more effective versus higher doses for enhancing the germination and growth characteristics of sunflower. In view of positive effect of gamma radiation of sunflower germination and growth characteristics, it is concluded that this techniques could possibly be used for the enhancement of germination, growth and ultimately yield in sunflower in areas where germination is low due to unfavorable conditions.