E6AP, an E3 ubiquitin ligase negatively regulates granulopoiesis by targeting transcription factor C/EBPα for ubiquitin-mediated proteasome degradation.

CCAAT/enhancer-binding protein alpha (C/EBPα) is an important transcription factor involved in granulocytic differentiation. Here, for the first time we demonstrate that E6-associated protein (E6AP), an E3 ubiquitin ligase targets C/EBPα for ubiquitin-mediated proteasome degradation and thereby negatively modulates its functions. Wild-type E6AP promotes ubiquitin dependent proteasome degradation of C/EBPα, while catalytically inactive E6-associated protein having cysteine replaced with alanine at amino-acid position 843 (E6AP-C843A) rather stabilizes it. Further, these two proteins physically associate both in non-myeloid (overexpressed human embryonic kidney epithelium) and myeloid cells. We show that E6AP-mediated degradation of C/EBPα protein expression curtails its transactivation potential on its target genes. Noticeably, E6AP degrades both wild-type 42 kDa CCAAT-enhancer-binding protein alpha (p42C/EBPα) and mutant isoform 30 kDa CCAAT-enhancer-binding protein alpha (p30C/EBPα), this may explain perturbed p42C/EBPα/p30C/EBPα ratio often observed in acute myeloid leukemia (AML). We show that overexpression of catalytically inactive E6AP-C843A in C/EBPα inducible K562- p42C/EBPα-estrogen receptor (ER) cells inhibits ß-estradiol (E2)-induced C/EBPα degradation leading to enhanced granulocytic differentiation. This enhanced granulocytic differentiation upon E2-induced activation of C/EBPα in C/EBPα stably transfected cells (ß-estradiol inducible K562 cells stably expressing p42C/EBPα-ER (K562-C/EBPα-p42-ER)) was further substantiated by siE6AP-mediated knockdown of E6AP in both K562-C/EBPα-p42-ER and 32dcl3 (32D clone 3, a cell line widely used model for in vitro study of hematopoietic cell proliferation, differentiation, and apoptosis) cells. Taken together, our data suggest that E6AP targeted C/EBPα protein degradation may provide a possible explanation for both loss of expression and/or functional inactivation of C/EBPα often experienced in myeloid leukemia.

Comparative study of chemical composition and antioxidant activity of fresh and dry rhizomes of turmeric (Curcuma longa Linn.).

The phytoconstituents of essential oil and ethanol oleoresin of fresh and dry rhizomes of turmeric (Curcuma longa Linn.) were analyzed by GC-MS. The major constituents were aromatic-turmerone (24.4%), alpha-turmerone (20.5%) and beta-turmerone (11.1%) in fresh rhizome and aromatic-turmerone (21.4%), alpha-santalene (7.2%) and aromatic-curcumene (6.6%) in dry rhizome oil. Whereas, in oleoresins, the major components were alpha-turmerone (53.4%), beta-turmerone (18.1%) and aromatic-turmerone (6.2%) in fresh and aromatic-turmerone (9.6%), alpha-santalene (7.8%) and alpha-turmerone (6.5%) in dry rhizome. Results showed that alpha-turmerone, a major component in fresh rhizomes is only minor one in dry rhizomes. Also, the content of beta-turmerone in dry rhizomes is less than a half amount found in fresh rhizomes. The antioxidant properties have been assessed by various lipid peroxidation assays as well as DPPH radical scavenging and metal chelating methods. The essential oil and ethanol oleoresin of fresh rhizomes have higher antioxidant properties as compared dry ones.

In situ simulation training for paediatric cardiorespiratory arrest: initial observations and identification of latent errors.

In response to a successful, although difficult resuscitation in one of our paediatric wards, we developed and implemented an educational program to improve the resuscitation skills, teamwork and safety climate in our multidisciplinary acute-care paediatric service. The program is ongoing and consists of didactic presentations, high-fidelity in situ simulation and facilitated debriefing to encourage reflective learning. The underlying goal, to provide this training to all staff over a two-year period, should be achieved by late 2011. In this preliminary report we describe teamwork difficulties that are commonly found during such training. These included inconsistent leadership behaviours, inadequate delegation of areas of responsibility, failure to communicate problems during the execution of technical tasks (such as difficulty opening the resuscitation trolley) and failure to challenge inadequate or inappropriate therapy (such as poor chest expansion during bag-mask ventilation). In addition, we unexpectedly discovered seven latent errors in our clinical environment during the first nine months of course delivery. The most disturbing of these was that participants repeatedly struggled to identify and overcome the locking-mechanism and tamper-proof device on a newly introduced resuscitation trolley.

Chemistry and in vitro antioxidant activity of volatile oil and oleoresins of black pepper (Piper nigrum).

Essential oil and oleoresins (ethanol and ethyl acetate) of Piper nigrum were extracted by using Clevenger and Soxhlet apparatus, respectively. GC-MS analysis of pepper essential oil showed the presence of 54 components representing about 96.6% of the total weight. beta-Caryophylline (29.9%) was found as the major component along with limonene (13.2%), beta-pinene (7.9%), sabinene (5.9%), and several other minor components. The major component of both ethanol and ethyl acetate oleoresins was found to contain piperine (63.9 and 39.0%), with many other components in lesser amounts. The antioxidant activities of essential oil and oleoresins were evaluated against mustard oil by peroxide, p-anisidine, and thiobarbituric acid. Both the oil and oleoresins showed strong antioxidant activity in comparison with butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) but lower than that of propyl gallate (PG). In addition, their inhibitory action by FTC method, scavenging capacity by DPPH (2,2'-diphenyl-1-picrylhydrazyl radical), and reducing power were also determined, proving the strong antioxidant capacity of both the essential oil and oleoresins of pepper.

Chemistry, antioxidant and antimicrobial investigations on essential oil and oleoresins of Zingiber officinale.

The essential oil and oleoresins (ethanol, methanol, CCl(4) and isooctane) of Zingiber officinale were extracted respectively by hydrodistillation and Soxhlet methods and subjected to GC-MS analysis. Geranial (25.9%) was the major component in essential oil; eugenol (49.8%) in ethanol oleoresin, while in the other three oleoresins, zingerone was the major component (33.6%, 33.3% and 30.5% for, methanol, CCl(4) and isooctane oleoresins, respectively). The antioxidant activity of essential oil and oleoresins were evaluated against mustard oil by peroxide, anisidine, thiobarbituric acid (TBA), ferric thiocyanate (FTC) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging methods. They were found to be better antioxidants than butylated hydroxyanisole (BHA). The antimicrobial properties were also studied using various food-borne pathogenic fungal and bacterial species. The essential oil and CCl(4) oleoresin showed 100% zone inhibition against Fusarium moniliforme. For other tested fungi and bacteriae, the essential oil and all oleoresins showed good to moderate inhibitory effects. Though, both essential oil and oleoresins were found to be effective, essential oil was found to be better than the oleoresins.

Preparation, X-ray crystallography, and thermal decomposition of some transition metal perchlorate complexes of hexamethylenetetramine.

The perchlorate complexes of manganese, nickel, and zinc with hexamethylenetetramine (HMTA) of the general formula [M(H2O-HMTA-H2O)2(H2O-ClO4)2(H2O)2] (where M=Mn, Ni, and Zn) have been prepared and characterized by X-ray crystallography. Thermal studies were undertaken using thermogravimetry (TG), differential thermal analysis (DTA), and explosion delay (DE) measurements. The kinetics of thermal decomposition of these complexes was investigated using isothermal TG data by applying isoconversional method. The decomposition pathways of the complexes have also been proposed. These were found to explode when subjected to higher temperatures.

Studies on essential oils: part 10; antibacterial activity of volatile oils of some spices.

The essential oils extracted from the seeds of seven spices, Anethum graveolens, Carum capticum, Coriandrum sativum, Cuminum cyminum, Foeniculum vulgare, Pimpinella anisum and Seseli indicum have been studied for antibacterial activity against eight pathogenic bacteria, causing infections in the human body. It has been found that the oil of C. capticum is very effective against all tested bacteria. The oil of C. cyminum and A. graveolens also gave similar results. These oils are equally or more effective when compared with standard antibiotics, at a very low concentration.

Propofol as a sole agent for paediatric day care diagnostic ophthalmic procedures: comparison with halothane anaesthesia.

BACKGROUND: Our aim was to study the feasibility of total intravenous anaesthesia with propofol in spontaneously breathing children undergoing ophthalmic procedures. METHODS: Fifty-five children (aged 6 months to 5 years) were randomly allocated to receive either propofol bolus (until loss of eyelash reflex) followed by infusion [group P (n=29)] or halothane 3-4% for induction, followed by 1-2% in 70% nitrous oxide and oxygen via face mask [group H (n=28)]. Dose for induction and maintenance, intraoperative adverse events, time to recovery (on an Observer's Assessment of Alertness/Sedation Scale, 5 at each level) and duration of procedure were recorded. All children in both groups, were anaesthetized successfully. RESULTS: 4.0 +/- 0.7 mg x kg(-1) and 5.1 +/- 1.0 mg x kg(-1) of propofol were required for loss of eyelash reflex and tolerance of the ophthalmic speculum, respectively. An infusion rate of 8.3 +/- 1.7 mg x kg(-1) x h(-1) was needed for maintenance of anaesthesia; 3.4 +/- 0.5%, 3.6 +/- 0.4% and 1.4 +/- 0.4% halothane was needed for induction, tolerance of the eye speculum and maintenance of anaesthesia, respectively. Induction and recovery were significantly faster with halothane compared with propofol [induction - 38.3 +/- 6.6 s (group H)/60.9 +/- 15.2 s (group P) (P < 0.001); recovery 12.8 +/- 4.6 min (group H)/27.0 +/- 23.3 min (group P) (P < 0.001)]. Apnoea, coughing and breath-holding were seen only in group H. Group P had significantly higher incidence of involuntary movements (minor degree) (n=6) (P < 0.01). CONCLUSIONS: Propofol is a feasible option for paediatric diagnostic ophthalmic procedures with the advantage over halothane of providing complete access to the eye.

Towards participatory environmental management?

While the mainstream approach to environmental management (EM) has tended to be centralized, adopting a narrow conception of 'environment', there is a growing body of literature supporting a participatory approach which is decentralized, community oriented and holistic in its view of the environment. This paper examines the main principles underlying this development and assesses the opportunities and constraints associated with it. It concludes that, while participation is conducive to a localized and inclusive approach to EM, many questions remain about the extent to which it is meaningful in practice or can be institutionalized.

Studies on energetic compounds. Part 16. Chemistry and decomposition mechanisms of 5-nitro-2,4-dihydro-3H-1,2,4-triazole-3-one (NTO).

The present review deals with the chemistry and thermolysis of NTO and plausible decomposition pathways have been described. The decomposition of 5-nitro-2,4-dihydro-3H-1,2,4-triazole-3-one (NTO) induced by X-ray, UV, laser, photochemical irradiation has also been discussed. High-speed photographic studies of the impact responses of NTO are also included. The thermal decomposition of labelled NTO has also been described here. Methods of detection as well as safe disposal of NTO have also been mentioned.

Studies on energetic compounds part 8 : thermolysis of salts of HNO(3) and HClO(4).

The thermolysis of various substituted ammonium salts of nitric and perchloric acids has been reviewed in the present communication. The mechanistic aspects of thermal decomposition of these salts have been discussed critically. It has been observed that the proton transfer process do play a major role during thermolysis of these salts. The plausible decomposition pathways have also been described.

Studies on energetic compounds. Part XI: preparation and thermolysis of polynitro organic compounds.

The thermolysis of high energetic polynitro organic compounds has been reviewed in the present communication.

FPAs look for solutions amid financial squeeze. Asia.

PIP: There are many reproductive health (RH) needs to be met in South Asia. However, while the countries who participated in the International Conference on Population and Development (ICPD) broadened their approach to RH and agreed upon the need to take care of RH, they have failed to provide the funds which they have pledged for RH. The broad perspective of the ICPD program of action, covering health and other components such as information, unsafe abortion, sexual health, and the abuse of women, makes it difficult for family planning associations (FPAs) to secure the funds they need to continue operating. Nongovernmental organizations (NGOs) are successfully achieving many things that governments could not. As such, governments should give NGOs enough time to become self-sustaining before cutting or withdrawing much needed funding. FPAs are currently trying to generate income through the sale of services and technical expertise. They are also tapping local businesses, philanthropists, and other local NGOs for support. Japan should be praised for maintaining its level of funding support.^ieng

New focus on advocacy in South Asia. Advocacy for reproductive health: South Asia.

PIP: Initiatives like Vision 2000, the International Conference on Population and Development in Cairo, and the Fourth World Conference on Women in Beijing have focused attention on the activities of regional family planning associations (FPAs) in South Asia. These activities include male acceptance of the responsibility for family life, youth involvement in program design and implementation, the promotion of gender equality, and increased public awareness about the value of the female child. The Beijing conference also directed attention to the problem of not allocating resources to problems recognized by governments. In the South Asia region funding levels have been falling, which impacts the maintenance of current programs. The South Asia Regional Bureau began to coordinate an information, education, and communication (IEC) and Advocacy Working Group in the region with the participation of IEC officers from all regional FPAs. The group will be planning IEC and advocacy activities based on the regional FPAs' goals and aspirations. The IEC and advocacy activities will be examined to identify existing skills and experiences of group participants. The group will also try to identify the activities of each FPA. The information gathered will point out the similarities in IEC and advocacy activities serving as a common ground for the region. Problems of IEC and advocacy comprise their subordinate structure and the failure to evaluate to show the impact of the activities. Better planning and organization and more holistic evaluation of program components should be achieved. The group will be self-directed responding to the IEC and advocacy needs, while also developing the professional and personal capacity of FPA staff to meet these needs.^ieng

Unmet need in family planning in South Asia Region.

Today's population in South Asia is estimated at 1.2 billion. With an average annual growth of 2%, it increases by more than 24 million people each year, the highest increment in the world. Despite recent improvements in the contraceptive prevalence rate, all countries in the region experience high levels of unmet need for contraception, Several of the region's characteristics have a bearing on the challenge of promoting and providing family planning services: women's status is particularly low; the persistence of son preference results in higher female than male mortality at all ages; the young age structure means an increasing number of people entering childbearing ages. Being predominantly rural, the region experiences shortages of trained health personnel as well as major problems of accessibility to basic health services.

Family planning encompasses sexuality -- an Asian perspective.

PIP: In India, where there is widespread ignorance about sexuality and a resistance to its open discussion, sexual and reproductive health issues must be integrated into family planning programs. It is not possible for staff to discuss birth spacing with clients without also addressing the sexual context. Sexual problems that are an appropriate focus for family planning programs include difficulty achieving orgasm, pain on intercourse, vaginismus, impotence, premature ejaculation, and loss of libido. An integrated program is especially necessary in Asian countries given women's hesitation to raise sexual issues. Family planning staff have been shaped by the same cultural taboos and must be helped, through training, to adopt an open, positive attitude toward human sexuality. This openness must extend to unmarried young people as well.^ieng