Synthesis of quinoline derivatives as diabetic II inhibitors and molecular docking studies

In searchof the potenttherapeutic agent as an α-glucosidase inhibitor, we have synthesized twenty-five analogs (1–25) of quinoline-based Schiff bases as an inhibitoragainst α-glucosidase enzyme under positive control acarbose (IC₅₀ = 38.45 ± 0.80 µM). From the activity profile it was foundthat analogs 1, 2, 3, 4, 11, 12 and 20with IC₅₀values 12.40 ± 0.40, 9.40 ± 0.30, 14.10 ± 0.40, 6.20 ± 0.30, 14.40 ± 0.40, 7.40 ± 0.20 and 13.20 ± 0.40 µMrespectively showed most potent inhibition among the series even than standard drug acarbose (IC₅₀ = 38.45 ± 0.80 µM). Here in the present study analog 4 (IC₅₀ = 6.20 ± 0.30 µM) was found with many folds better α-glucosidase inhibitory activity than the reference drug. Eight analogs like 5, 7, 8, 16, 17, 22, 24 and 25 among the whole series displayed less than 50% inhibition. The substituents effects on phenyl ring thereby superficially established through SAR study. Binding interactions of analogs and the active site of ligands proteins were confirmed through molecular docking study. Spectroscopic techniques like ¹H NMR, ¹³C NMR and ESIMS were used for characterization.     

Development of a novel inducer for EBV lytic therapy

Epstein-Barr virus (EBV) is a human herpesvirus that infects over 90% of the world's population that persists as a latent infection in various lymphoid and epithelial malignancies. The total number of EBV associated malignancies is estimated to exceed 200,000 new cancers per year. Current chemotherapeutic treatments of EBV-positive cancers include broad-spectrum cytotoxic drugs that ignore the EBV positive status of tumors and have limited safety and selectivity. In an effort to develop new and more efficacious molecules for inducing EBV reactivation, we have developed high-throughput screening assays to identify a class of small molecules (referred to as the C60 series) that efficiently activate the EBV lytic cycle in multiple latency types, including lymphoblastoid and nasopharyngeal carcinoma cell lines. In this paper we report our preliminary structure activity relationship studies and demonstrate reactivation of EBV in the SNU719 gastric carcinoma mouse model and the AGS-Akata gastric carcinoma mouse model.     

The responses of Apis mellifera jemenitica to different artificial queen rearing techniques

In the current study, we investigated if any variations exist in acceptance rate of grafted larvae and quality of queens reared in different queen cell cup sizes, between wet and dry grafting and between queen right and queen less conditions of A. m. jemenitica colonies. The acceptance rate of grafted larvae in different queen cell cup sizes (7.0 mm, 7.5 mm, 8.0 mm, 8.5 mm) were varying from 69 to 71% and the variations were not significant among the different queen cups sizes but averagely lower than the acceptances recorded for other races. Out of the 172 dry grafted larvae, only 56.4% of them were accepted while in wet grafting out of 174 grafted larvae 77.01% were accepted. Regarding the rate of sealing, 48.84% and 71.84% of them sealed for dry and wet grafts, respectively. The observed variation in the rate of acceptance and sealing were significant (N = 346, df = 1, P < 0.0001) between the two techniques. However, there was no significant difference in fresh weight of emerged queens between the two grafting methods. Out of the 324 grafted larvae given to queen right and queen less starter colonies each; 106 (32.72%) and 252 (73.68%) were accepted in queen right and queen less starter colonies, respectively and the variation was highly significant at P < 0.0001. The total number of sealed pupae were 82 (25.31%) and 216 (63.16%) for queen right and queen less colonies, respectively and the variations was significant at P < 0.0001. From the study it can be concluded that A. m. jemenitica colonies can rear significantly more queens under wet grafting and in queen less colonies conditions than dry grafting and queen right conditions     

Risk factors associated with E. coli causing neonatal calf diarrhea

Calf diarrhea is one of the major health challenges in cattle herds. The bacteriological examination of fecal samples collected from apparently healthy and diarrheic calves' revealed isolation of 26 E. coli isolates out of 56 calves with an incidence of 46.4%. Serogroups O1, O26, O44, O55, O115, O119, O125, O146, and O151 were identified from the collected fecal samples. Using PCR all isolates was positive for ompA gene species specific for E. coli. While stx1 and eaeA genes detected with incidence of 3.8 and 19.2% respectively from the isolates. The presence of stx2 gene was negative in the fecal isolates. Among colostrum samples 4 E. coli isolates were detected and serogrouped to O26, O55 and O119. They were negative for eaeA, stx1 and stx2 except strain number 4 (O55) was positive for stx1. E. coli strains were sensitive to norfloxacin (80.7%) and resistant to ampicillin and cefotaxime (100% each). Based on our findings, there was no association between occurrence of E. coli and age of calf (2–14 days), while bottle feeding calf colostrum may be a source of E. coli contamination.     

Blepharis saudensis (Acanthaceae), a new species from Saudi Arabia

Blepharis saudensis, from small islands in the Red Sea of Jazan Provence, Saudi Arabia, is described as a new species and illustrated. This species differs from other known species in this genus by having a combination of long stems, oblong-lanceolate to linear leaves with entire margins and pubescence.     

The genetic association study of TP53 polymorphisms in Saudi obese patients

Obesity is a multifactorial metabolic disorder characterized by low grade chronic inflammation. Rare and novel mutations in genes which are vital in several key pathways have been reported to alter the energy expenditure which regulates body weight. The TP53 or p53 gene plays a prominent role in regulating various metabolic activities such as glycolysis, lipolysis, and glycogen synthesis. Recent genome-wide association studies reported that tumor suppressor gene p53 variants play a critical role in the predisposition of type 2 diabetes and obesity. Till date, no reports are available from the Arabian population; hence the present study was intended to assess the association between p53 variants with risk of obesity development in the Saudi population. We have selected three p53 polymorphisms, rs1642785 (C > G), and rs9894946 (A > G), and rs1042522 (Pro72Arg; C > G) and assessed their association with obesity risk in the Saudi population. Phenotypic and biochemical parameters were also evaluated to check their association with p53 genotypes and obesity. Genotyping was carried out on 136 obese and 122 normal samples. We observed that there is significantly increased prevalence p52 Pro72Arg (rs1042522) polymorphism in obese persons when compared to controls at GG genotype in overall comparison (OR: 2.169, 95% CI: 1.086-4.334, p = 0.02716). Male obese subjects showed three-fold higher risk at GG genotype (OR: 3.275, 95% CI: 1.230-8.716, p = 0.01560) and two-fold risk at G allele (OR: 1.827, 95% CI: 1.128-2.958, p = 0.01388) of p53 variant Pro72Arg respectively. This variant has also shown significant influence on cholesterol, LDL level, and random insulin levels in obese subjects (p ≤ 0.05). In conclusion, p53 Pro72Arg variant is highly prevalent among obese individuals and may act as a genetic modifier for obesity development among Saudis.     

Genetic variations of NOD2 and MD2 genes in hepatitis B virus infection

Objectives: Nucleotide oligomerization domain 2 (NOD2) and myeloid differentiation protein 2 (MD-2) have crucial roles in the innate immune system. NOD2 is a member of the NOD-like receptor (NLR) family of pattern recognition receptors (PRRs), while MD-2 is a co-receptor for Toll-like receptor 4 (TLR4), which comprises another group of PRRs. Genetic variations in the NOD2 and MD-2 genes may be susceptibility factors to viral pathogens including hepatitis B virus (HBV). We investigated whether polymorphisms at NOD2 (rs2066845 and rs2066844) or at MD-2 (rs6472812 and rs11466004) were associated with susceptibility to HBV infection and advancement to related liver complications in a Saudi Arabian population. Methods: A total of 786 HBV-infected patients and 600 healthy uninfected controls were analyzed in the present study. HBV-infected patients were categorized into three groups based on the clinical stage of the infection: inactive HBV carriers, active HBV carriers, and patients with liver cirrhosis + hepatocellular carcinoma (HCC). Results: All four SNPs were significantly associated with susceptibility to HBV infection although none of the SNPs tested in NOD2 and MD-2 were significantly associated with persistence of HBV infection. We found that HBV-infected patients that were homozygous CC for rs2066845 in the NOD2 gene were at a significantly increased risk of progression to HBV-related liver complications (Odds Ratio = 7.443 and P = 0.044). Furthermore, haplotype analysis found that the rs2066844-rs2066845 C-G and T-G haplotypes at the NOD2 gene and four rs6472812-rs11466004 haplotypes (G-C, G-T, A-C, and A-T) at the MD-2 gene were significantly associated with HBV infection in the affected cohort compared to those found in our control group. Conclusion: We found that the single nucleotide polymorphisms rs2066844 and rs2066845 at NOD2 and rs6472812 and rs11466004 at MD-2 were associated with susceptibility to HBV infection in a Saudi population.     

Field estimates of fitness costs of the pace‐of‐life in an endangered damselfly

Theory predicts that within‐population differences in the pace‐of‐life can lead to cohort splitting and produce marked intraspecific variation in body size. Although many studies showed that body size is positively correlated with fitness, many argue that selection for the larger body is counterbalanced by opposing physiological and ecological selective mechanisms that favour smaller body. When a population split into cohorts with different paces of life (slow or fast cohort), one would expect to detect the fitness–size relationship among and within cohorts, that is, (a) slower‐developing cohort has larger body size and higher fitness than faster‐developing cohort, and (b) larger individuals within each cohort show higher fitness than smaller individuals. Here, we test these hypotheses in capture–mark–recapture field surveys that assess body size, lifespan, survival and lifetime mating success in two consecutive generations of a partially bivoltine aquatic insect, Coenagrion mercuriale, where the spring cohort is slower‐developing than the autumn cohort. As expected, body size was larger in the slow‐developing cohort, which is consistent with the temperature‐size rule and also with the duration of development. Body size seasonal variation was greater in slow‐developing cohort most likely because of the higher variation in age at maturity. Concordant with theory, survival probability, lifespan and lifetime mating success were higher in the slow‐developing cohort. Moreover, individual body size was positively correlated with survival and mating success in both cohorts. Our study confirms the fitness costs of fast pace‐of‐life and the benefits of larger body size to adult fitness.     

Unwanted Horse Population in Illinois: Perceptions of Horse Owners,Non-Horse Owners,and Equine Industry Stakeholders

This paper presents the results of an investigation to determine perceptions, awareness, and knowledge of the unwanted horse population in Illinois from the viewpoint of horse owners, non-horse owners, and equine industry stakeholders. A questionnaire included items that pertained to knowledge of current legislation, equine background, current methods of controlling the unwanted horse population, and methods that respondents believe would reduce the unwanted horse population in Illinois. Results indicated that 58% of horse owners viewed horses as companion animals. Respondents perceived financial hardship to be the major reason why horses become unwanted. Current methods of managing unwanted horse populations were found to be ineffective. Reducing the costs of euthanasia and carcass disposal, allowing processing facilities to reopen in Illinois, and increasing the availability of gelding programs emerged as the most effective ways to manage the unwanted horse population. Results of this survey may lead to greater awareness of the unwanted horse population in Illinois. Furthermore, these results may lead to discussions about future legislation in the State designed to support and manage unwanted horses.     

The role of chick Ebf genes in the mediolateral patterning of the somites

This study was conducted to check whether the three chick Early B‐cell Factor (Ebf) genes, particularly cEbf1, would be targets for Shh and Bmp signals during somites mediolateral (ML) patterning. Tissue manipulations and gain and loss of function experiments for Shh and Bmp4 were performed and the results revealed that cEbf1 expression was initiated in the cranial presomitic mesoderm by low dose of Bmp4 from the lateral mesoderm and maintained in the ventromedial part of the epithelial somite and the medial sclerotome by Shh from the notochord; while cEbf2/3 expression was induced and maintained by Bmp4 and inhibited by high dose of Shh. To determine whether Ebf1 plays a role in somite patterning, transfection of a dominant‐negative construct was carried out; this showed suppression of cPax1 expression in the medial sclerotome and upregulation and medial expansion of cEbf3 and cPax3 expression in sclerotome and dermomyotome, respectively, suggesting that Ebf1 is important for ML patterning. Thus, it is possible that low doses of Bmp4 set up Ebf1 expression which, together with Shh from the notochord, leads to establishment of the medial sclerotome and suppression of lateral identities. These data also conclude that Bmp4 is required in both the medial and lateral domain of the somitic mesoderm to keep the ML identity of the sclerotome through maintenance of cEbf gene expression. These striking findings are novel and give a new insight on the role of Bmp4 on mediolateral patterning of somites.