Mechanistic insights into the C₅₅-P targeting lipopeptide antibiotics revealed by structure-activity studies and high-resolution crystal structures

The continued rise of antibiotic resistance is a global concern that threatens to undermine many aspects of modern medical practice. Key to addressing this threat is the discovery and development of new antibiotics that operate by unexploited modes of action. The so-called calcium-dependent lipopeptide antibiotics (CDAs) are an important emerging class of natural products that provides a source of new antibiotic agents rich in structural and mechanistic diversity. Notable in this regard is the subset of CDAs comprising the laspartomycins and amphomycins/friulimicins that specifically target the bacterial cell wall precursor undecaprenyl phosphate (C(55)-P). In this study we describe the design and synthesis of new C(55)-P-targeting CDAs with structural features drawn from both the laspartomycin and amphomycin/friulimicin classes. Assessment of these lipopeptides revealed previously unknown and surprisingly subtle structural features that are required for antibacterial activity. High-resolution crystal structures further indicate that the amphomycin/friulimicin-like lipopeptides adopt a unique crystal packing that governs their interaction with C(55)-P and provides an explanation for their antibacterial effect. In addition, live-cell microscopy studies provide further insights into the biological activity of the C(55)-P targeting CDAs highlighting their unique mechanism of action relative to the clinically used CDA daptomycin

Collection, identification of Iranian fish parasites for “Iranian parasitology Museum”

Abstract: Identification and classification of aquatic parasites are more important by the day. Aquaculture development are faced with parasites previously "not pathogenic in normal conditions, but under certain conditions bacame diseases and have caused heavy losses to the aquaculture farms. The results of these studies recognize the importance of parasites in fish production has clear economic value. Before any action for economic aquatic breeding the parasites that can infect the fish have been identified and methods of control will be drawn. The current project is a part (the fishes) of the project Parasitology Museum in the Faculty of Veterinary medicine of Tehran University. In the first phase of the project, it was planned the fish parasites from different regions of the country were collected and the Iranian Fish Parasites Data Base has also set up. Required experts and various specialties were organized for implementation an recognation of the collected parasitese. The province executive and coordination necessary and the methods of sampling were discussed after a day of training workshop was held at the Faculty of Veterinary medicine of Tehran University. Due to the lack of funds needed to coordinate the implementation, it was conducted that the parasite specimens collected from other projects. In the first phase of projects 261 parasites various have been sent. Collected samples received a temporary code and announced. In the laboratory the specimens categoried and the shape designed and finally the consultants send the final identification of the parasites. Posted parasites according to the latest international standards are maintained. Each parasite has a unique code that represents the name of the sender, verification of the final consultant, host and fishing region. Simultaneously, reported fish parasites from 1327 AD (1949 AD) were collected to create a database, they classified to be placed on the site inPersian and English. Fish parasites that have been reported are available in four types: final report of the research projects conducted at research centers and universities, student theses, abstracts published in scientific conferences and finally "published in national and international research journals. “Iranian fish parasitesd database” included: Founders and Pioneers Monument, Iranian fish parasite fauna, History, Search, Resources, Executive Committee, links, News. Researchers can search through the five “key words”: the name of the parasite, the parasite class branch, region or provincial fishing, infected of host organ. After achieving the desired list of parasites, descriptions, and specifications can be observe. The resource section lists some of the articles published and will be visible as a “pdf”

Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes

Underlying genetic determinants contribute to developing type 2 diabetes (T2D) future diseases. The present study aimed to identify which genetic variants are associated with the incident of the major T2D co-morbid disease. First, we conducted a discovery study by investigating the genetic associations of comorbid diseases within the framework of the Utrecht Cardiovascular Pharmacogenetic studies by turning information of > 25 years follow-up data of 1237 subjects whom were genotyped and included in the discovery study. We performed Cox proportional-hazards regression to examine associations between genetic variants and comorbid diseases including cardiovascular diseases (CVD), chronic eye disease, cancer, neurologic diseases and chronic kidney disease. Secondly, we replicated our findings in two independent cohorts consisting of 1041 subjects. Finally, we performed a meta-analysis by combining the discovery and two replication cohorts. We ascertained 390 (39.7%) incident cases of CVD, 182 (16.2%) of chronic eye disease, 155 (13.8%) of cancer, 31 (2.7%) of neurologic disease and 13 (1.1%) of chronic kidney disease during a median follow-up of 10.2 years. In the discovery study, we identified a total of 39 Single Nucleotide Polymorphisms (SNPs) associated with comorbid diseases. The replication study, confirmed that rs1870849 and rs8051326 may play a role in the incidence of chronic eye disease in T2D patients. Half of patients developed at least one comorbid disease, with CVD occurring most often and earliest followed by chronic eye disease. Further research is needed to confirm the associations of two associated SNPs with chronic eye disease in T2D

CIGARETTE DEMAND IN SOUTH AFRICA OVER 1996-2006: THE ROLE OF PRICE, INCOME AND HEALTH AWARENESS

The study seeks to re-investigate the role of price, income and health awareness in the evolution of South African cigarette demand over the period 1996 to 2006. At first glance, rising cigarette prices appear to have played an important role in reducing cigarette consumption over the sample period, especially during the late 90s. But how dependent is the impact of price increases on general economic conditions and overall health awareness among smokers? Health awareness, in particular, has not received sufficient attention in the South African context, due to a lack of data. Previous estimates of price and income elasticities of cigarette demand are based on long annual time series data, which do not allow for changes in underlying tastes and preferences. The paper attempts to disentangle the forces of price, income, health awareness and policy intervention using a quarterly data set. In addition, the study also cautions against the upward bias in estimates derived from formal cigarette sales data - in the light of increasing illicit cigarette volumes in South Africa. Copyright (c) 2008 The Author. Journal compilation (c) Economic Society of South Africa 2008.