Frequency and determinants of intracranial atherosclerotic stroke in urban Pakistan.

BACKGROUND: Intracranial atherosclerosis (ICAD) is a frequent underlying mechanism of ischemic stroke. There is little direct evidence on its frequency and determinants from regions of high prevalence. This study explores the conventional and socioeconomic risk factors of ICAD in a South Asian population. METHODS: The Karachi Intracranial Stenosis Study is a case-control study of 313 cases of ischemic stroke secondary to ICAD and 331 controls enrolled from 4 major hospitals in Karachi, Pakistan. Stroke subtype was verified by a vascular neurologist using the Trial of Org 10172 in Acute Stroke Treatment classification. Relationships of conventional and socioeconomic risk factors with ICAD-related strokes are reported by calculating odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS: ICAD was the cause of stroke in 81.1% cases with large-artery atherosclerosis and 19.5% of all stroke events. Along with risk factors like history of hypertension (OR, 3.33; CI, 2.31-4.78), history of diabetes (OR, 2.29; CI, 1.56-3.35), use of tobacco (OR, 1.49; CI, 1.03-2.16), waist-to-hip ratio (OR, 1.58; CI, 1.04-2.41), and family history of stroke (OR, 1.89; CI, 1.21-2.95), other significant social determinants of ICAD strokes were monthly income (OR, 1.59; CI, 1.01-2.51), unemployment (OR, 2.15; CI, 1.21-3.83), and chronic stress (OR, 3.67; CI, 2.13-6.34). These social determinants were independent predictors of the risk of ICAD, in addition to those described in other world populations. CONCLUSIONS: ICAD accounted for one fifth of all strokes making it the most common ischemic stroke mechanism. In addition to aggressive risk factor control, data also indicated broader holistic efforts on ameliorating inequity, unemployment, and stress reduction to reduce stroke because of ICAD.

Implications of metal accumulation mechanisms to phytoremediation.

BACKGROUND, AIM, AND SCOPE: Trace elements (heavy metals and metalloids) are important environmental pollutants, and many of them are toxic even at very low concentrations. Pollution of the biosphere with trace elements has accelerated dramatically since the Industrial Revolution. Primary sources are the burning of fossil fuels, mining and smelting of metalliferous ores, municipal wastes, agrochemicals, and sewage. In addition, natural mineral deposits containing particularly large quantities of heavy metals are found in many regions. These areas often support characteristic plant species thriving in metal-enriched environments. Whereas many species avoid the uptake of heavy metals from these soils, some of them can accumulate significantly high concentrations of toxic metals, to levels which by far exceed the soil levels. The natural phenomenon of heavy metal tolerance has enhanced the interest of plant ecologists, plant physiologists, and plant biologists to investigate the physiology and genetics of metal tolerance in specialized hyperaccumulator plants such as Arabidopsis halleri and Thlaspi caerulescens. In this review, we describe recent advances in understanding the genetic and molecular basis of metal tolerance in plants with special reference to transcriptomics of heavy metal accumulator plants and the identification of functional genes implied in tolerance and detoxification. RESULTS: Plants are susceptible to heavy metal toxicity and respond to avoid detrimental effects in a variety of different ways. The toxic dose depends on the type of ion, ion concentration, plant species, and stage of plant growth. Tolerance to metals is based on multiple mechanisms such as cell wall binding, active transport of ions into the vacuole, and formation of complexes with organic acids or peptides. One of the most important mechanisms for metal detoxification in plants appears to be chelation of metals by low-molecular-weight proteins such as metallothioneins and peptide ligands, the phytochelatins. For example, glutathione (GSH), a precursor of phytochelatin synthesis, plays a key role not only in metal detoxification but also in protecting plant cells from other environmental stresses including intrinsic oxidative stress reactions. In the last decade, tremendous developments in molecular biology and success of genomics have highly encouraged studies in molecular genetics, mainly transcriptomics, to identify functional genes implied in metal tolerance in plants, largely belonging to the metal homeostasis network. DISCUSSION: Analyzing the genetics of metal accumulation in these accumulator plants has been greatly enhanced through the wealth of tools and the resources developed for the study of the model plant Arabidopsis thaliana such as transcript profiling platforms, protein and metabolite profiling, tools depending on RNA interference (RNAi), and collections of insertion line mutants. To understand the genetics of metal accumulation and adaptation, the vast arsenal of resources developed in A. thaliana could be extended to one of its closest relatives that display the highest level of adaptation to high metal environments such as A. halleri and T. caerulescens. CONCLUSIONS: This review paper deals with the mechanisms of heavy metal accumulation and tolerance in plants. Detailed information has been provided for metal transporters, metal chelation, and oxidative stress in metal-tolerant plants. Advances in phytoremediation technologies and the importance of metal accumulator plants and strategies for exploring these immense and valuable genetic and biological resources for phytoremediation are discussed. RECOMMENDATIONS AND PERSPECTIVES: A number of species within the Brassicaceae family have been identified as metal accumulators. To understand fully the genetics of metal accumulation, the vast genetic resources developed in A. thaliana must be extended to other metal accumulator species that display traits absent in this model species. A. thaliana microarray chips could be used to identify differentially expressed genes in metal accumulator plants in Brassicaceae. The integration of resources obtained from model and wild species of the Brassicaceae family will be of utmost importance, bringing most of the diverse fields of plant biology together such as functional genomics, population genetics, phylogenetics, and ecology. Further development of phytoremediation requires an integrated multidisciplinary research effort that combines plant biology, genetic engineering, soil chemistry, soil microbiology, as well as agricultural and environmental engineering.

Comparative phylogenetic analysis of small GTP-binding genes of model legume plants and assessment of their roles in root nodules.

Small GTP-binding genes play an essential regulatory role in a multitude of cellular processes such as vesicle-mediated intracellular trafficking, signal transduction, cytoskeletal organization, and cell division in plants and animals. Medicago truncatula and Lotus japonicus are important model plants for studying legume-specific biological processes such as nodulation. The publicly available online resources for these plants from websites such as http://www.ncbi.nih.gov, http://www.medicago.org, http://www.tigr.org, and related sites were searched to collect nucleotide sequences that encode GTP-binding protein homologues. A total of 460 small GTPase sequences from several legume species including Medicago and Lotus, Arabidopsis, human, and yeast were phyletically analysed to shed light on the evolution and functional characteristics of legume-specific homologues. One of the main emphases of this study was the elucidation of the possible involvement of some members of small GTPase homologues in the establishment and maintenance of symbiotic associations in root nodules of legumes. A high frequency of vesicle-mediated trafficking in nodules led to the idea of a probable subfunctionalization of some members of this family in legumes. As a result of the analyses, a group of 10 small GTPases that are likely to be mainly expressed in nodules was determined. The sequences determined as a result of this study could be used in more detailed molecular genetic analyses such as creation of RNA interference silencing mutants for further clarification of the role of GTPases in nodulation. This study will also assist in furthering our understanding of the evolutionary history of small GTPases in legume species.

Using phytoremediation technologies to upgrade waste water treatment in Europe.

GOAL, SCOPE AND BACKGROUND: One of the burning problems of our industrial society is the high consumption of water and the high demand for clean drinking water. Numerous approaches have been taken to reduce water consumption, but in the long run it seems only possible to recycle waste water into high quality water. It seems timely to discuss alternative water remediation technologies that are fit for industrial as well as less developed countries to ensure a high quality of drinking water throughout Europe. MAIN FEATURES: The present paper discusses a range of phytoremediation technologies to be applied in a modular approach to integrate and improve the performance of existing wastewater treatment, especially towards the emerging micro pollutants, i.e. organic chemicals and pharmaceuticals. This topic is of global relevance for the EU. RESULTS: Existing technologies for waste water treatment do not sufficiently address increasing pollution situation, especially with the growing use of organic pollutants in the private household and health sector. Although some crude chemical approaches exist, such as advanced oxidation steps, most waste water treatment plants will not be able to adopt them. The same is true for membrane technologies. DISCUSSION: Incredible progress has been made during recent years, thus providing us with membranes of longevity and stability and, at the same time, high filtration capacity. However, these systems are expensive and delicate in operation, so that the majority of communities will not be able to afford them. Combinations of different phytoremediation technologies seem to be most promising to solve this burning problem. CONCLUSIONS: To quantify the occurrence and the distribution of micropollutants, to evaluate their effects, and to prevent them from passing through wastewater collection and treatment systems into rivers, lakes and ground water bodies represents an urgent task for applied environmental sciences in the coming years. RECOMMENDATIONS: Public acceptance of green technologies is generally higher than that of industrial processes. The EU should stimulate research to upgrade existing waste water treatment by implementing phytoremediation modules and demonstrating their reliability to the public.

Pattern of nosocomial infection in two intensive care units of a tertiary care hospital in Karachi.

OBJECTIVE: To determine the pattern of nosocomial infections in two ICUs' of a teaching hospital in terms of frequency, common sites of infection, the pathogens involved and the antibiotic sensitivity patterns. DESIGN: Observational study. PLACE AND DURATION OF STUDY: It was conducted in two medical ICUs (Neurology and Nephrology) of a public tertiary care hospital i.e. Civil Hospital, Karachi, from June to November 2004. PATIENTS AND METHODS: Data was collected prospectively on patients suspected to have developed nosocomial infection after 48 hours of admission to the ICU according to objective. RESULTS: There were 101 cases of suspected nosocomial infection out of a total of 254 patients. The frequency of nosocomial infection was 39.7%. UTI developed in 44.6%, while 27% had blood stream infection, and 21% had pneumonia. Each of the three major sites of infection was strongly associated with the use of invasive devices. Escherichia (E.) coli was the most common organism isolated followed by Pseudomonas aeruginosa and Klebsiella. E. coli and Klebsiella showed a maximum sensitivity to Imipenem followed by Tazocin (pipericillin + tazobactam). Pseudomonas aeruginosa was sensitive to Amikacin and Fosfomycin. CONCLUSION: The high frequency of nosocomial infection suggests that more strict measures regarding invasive devices should be taken in future to control the infection and limit the emergence of antibiotic resistant organisms.

The role of ADP-ribosylation factor and SAR1 in vesicular trafficking in plants.

Ras-like small GTP binding proteins regulate a wide variety of intracellular signalling and vesicular trafficking pathways in eukaryotic cells including plant cells. They share a common structure that operates as a molecular switch by cycling between active GTP-bound and inactive GDP-bound conformational states. The active GTP-bound state is regulated by guanine nucleotide exchange factors (GEF), which promote the exchange of GDP for GTP. The inactive GDP-bound state is promoted by GTPase-activating proteins (GAPs) which accelerate GTP hydrolysis by orders of magnitude. Two types of small GTP-binding proteins, ADP-ribosylation factor (Arf) and secretion-associated and Ras-related (Sar), are major regulators of vesicle biogenesis in intracellular traffic and are founding members of a growing family that also includes Arf-related proteins (Arp) and Arf-like (Arl) proteins. The most widely involved small GTPase in vesicular trafficking is probably Arf1, which not only controls assembly of COPI- and AP1, AP3, and AP4/clathrin-coated vesicles but also recruits other proteins to membranes, including some that may be components of further coats. Recent molecular, structural and biochemical studies have provided a wealth of detail of the interactions between Arf and the proteins that regulate its activity as well as providing clues for the types of effector molecules which are controlled by Arf. Sar1 functions as a molecular switch to control the assembly of protein coats (COPII) that direct vesicle budding from ER. The crystallographic analysis of Sar1 reveals a number of structurally unique features that dictate its function in COPII vesicle formation. In this review, I will summarize the current knowledge of Arf and Sar regulation in vesicular trafficking in mammalian and yeast cells and will highlight recent advances in identifying the elements involved in vesicle formation in plant cells. Additionally, I will briefly discuss the similarities and dissimilarities of vesicle traffic in plant, mammalian and yeast cells.

Legume small GTPases and their role in the establishment of symbiotic associations with Rhizobium spp.

Small GTP-binding genes act as molecular switches regulating myriad of cellular processes including vesicle-mediated intracellular trafficking, signal transduction, cytoskeletal reorganization and cell division in plants and animals. Even though these genes are well conserved both functionally and sequentially across whole Eukaryotae, occasional lineage-specific diversification in some plant species in terms of both functional and expressional characteristics have been reported. Hence, comparative phyletic and correlative functional analyses of legume small GTPases homologs with the genes from other Metazoa and Embryophyta species would be very beneficial for gleaning out the small GTPases that could have specialized in legume-specific processes; e.g., nodulation. The completion of genome sequences of two model legumes, Medicago truncatula and Lotus japonicus will significantly improve our knowledge about mechanism of biological processes taking place in legume-rhizobia symbiotic associations. Besides, the need for molecular switches coordinating busy cargo-trafficking between symbiosis partners would suggest a possible subfunctionalization of small GTPases in Fabaceae for these functions. Therefore, more detailed investigation into the functional characteristics of legume small GTPases would be helpful for the illumination of the events initialized with the perception of bacteria by host, followed by the formation of infection thread and the engulfment of rhizobial bacteria, and end with the senescence of nitrogen-fixing organelles, nodules. In summary, a more thorough functional and evolutionary characterization of small GTPases across the main lineages of Embryophyta is significant for better comprehension of evolutionary history of Plantae, that is because, these genes are associated with multitude of vital biological processes including organogenesis.