K<Emphasis Type="Italic">i</Emphasis> DoQ: using docking based energy scores to develop ligand based model for predicting antibacterials

Background  

Identification of novel drug targets and their inhibitors is a major challenge in the field of drug designing and development. Diaminopimelic acid (DAP) pathway is a unique lysine biosynthetic pathway present in bacteria, however absent in mammals. This pathway is vital for bacteria due to its critical role in cell wall biosynthesis. One of the essential enzymes of this pathway is dihydrodipicolinate synthase (DHDPS), considered to be crucial for the bacterial survival. In view of its importance, the development and prediction of potent inhibitors against DHDPS may be valuable to design effective drugs against bacteria, in general.     

New World Stictocladius Edwards (Diptera: Chironomidae)

The orthocladiine Chironomidae genus Stictocladius Edwards was described originally from South America. Although recognised subsequently as present also in Australia and New Zealand, the true diversity in the Neotropics has remained unclear. After more than a decade of collections of both isolated adults and aquatic immature stages, we can recognise several new taxa and associate some immature stages. Thus, we describe Stictocladius prati n. sp. as male, female, pupa and larva; Stictocladius acutus n. sp. and Stictocladius acrilobus n. sp. as male, female and pupa; Stictocladius fimbriatus n. sp. as male and female; Stictocladius fovigus n. sp. and Stictocladius nudiventer n. sp. as male and pupa; and Stictocladius privicalcar n. sp. and Stictocladius prostatus n. sp. each as male imago alone. The male and female of Stictocladius pulchripennis Edwards is redescribed and the pupa described. The male and female of Stictocladius flavozonatus Edwards and the male of Stictocladius calonotum Edwards are described. Five pupal types are described: Stictocladius sp. A (near S. acrilobus), Stictocladius sp. B (possibly S. calonotum), Stictocladius sp. C (near S. calonotum), Stictocladius sp. D (possibly S. flavozonatus) and Stictocladius sp. E with uncertain affinity. A larva from Chile of the Stictocladius ??sofour type?? (Stictocladius sp. F) and an unreared larva from North America (Stictocladius sp. G) possibly belonging to S. acutus are described. Keys to named Neotropical male and female imagines of Stictocladius and to all pupal forms of Neotropical Stictocladius are provided. Some data concerning fourth instars of Stictocladius are presented. Means of differentiation from putative sister taxon Lopescladius are discussed.     

Contamination of Floodplain Soils along the Wupper River,Germany, with As,Co, Cu,Ni, Sb,and Zn and the Impact of Pre-definite Redox Variations on the Mobility of These Elements

This study demonstrates that floodplain soils of the River Wupper, Germany, are seriously contaminated with metal(loid)s. We used an automated biogeochemical microcosm system allowing controlled variation of redox potential (E_H) to assess the impact of pre-definite redox conditions on the dynamics of arsenic (As), cobalt (Co), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), antimony (Sb), and zinc (Zn) in homogenized soil material taken from an acid floodplain soil. The concentrations of Co, Cu, Mn, Ni, Sb, and Zn in soil solution were low at low E_H, possibly due to the precipitation of metal sulfides, and increased with rising E_H, presumably caused by their association with dissolved organic carbon (DOC). A significant positive correlation between metal/DOC-ratio and E_H indicated that the binding of the metals to DOC shifted from stronger to weaker when E_H rose. Decreasing As concentrations with increasing E_H in soil solution indicated co-precipitation with Fe(hydr)oxides and/or oxidation of more soluble As(III) to less soluble As(V) during oxidation. The other studied elements seemed not to co-precipitate with newly formed Fe(hydr)oxides when E_H rose, possibly due to the prevailing low pH. In the future, the specific role of DOC and sulfur chemistry on metal(loid) dynamics should be elucidated more fully, and similar studies should be conducted with additional frequently flooded soils worldwide to verify these results.     

The teaching of prosthodontic care for older people: a non-rote philosophy

This essay complements that de Baat et al¹ in the last issue with emphasis on the importance of the variability between individual older people. The consequent need for an open minded approach towards planning Prosthodontics is discussed, based on each patient's motivation for aesthetics, function, comfort and self esteem. Both functional expectations and motivation to learn effective health behaviour vary widely, and evaluation of both is essential for realistic planning because further tooth loss and the need for partial dentures occur so frequently. The consequent variation in plans raises the question – which are the strategic teeth to maintain a stable dental occlusion or a future tooth stabilised denture? For undergraduates this demands a non-rote approach to learning.     

5-Fluorouracil-induced cardiotoxicity mimicking myocardial infarction: a case report

Background  

Severe cardiotoxicity is a documented, but very unusual side-effect of intravenous 5-fluorouracil therapy. The mechanism producing cardiotoxicity is poorly understood.     

The Fragilis interferon-inducible gene family of transmembrane proteins is associated with germ cell specification in mice

Background  

Specification of primordial germ cells in mice depends on instructive signalling events, which act first to confer germ cell competence on epiblast cells, and second, to impose a germ cell fate upon competent precursors. fragilis, an interferon-inducible gene coding for a transmembrane protein, is the first gene to be implicated in the acquisition of germ cell competence.     

The molecular evolution of the alcohol dehydrogenase and alcohol dehydrogenase-related genes in the Drosophila melanogaster species subgroup

The DNA sequences of the Adh genes of three members of the Drosophila melanogaster species subgroup have been determined. This completes the Adh sequences of the eight species of this subgroup. Two species, D. yakuba and D. teissieri, possess processed Adh pseudogenes. In all of the species of the subgroup, a gene of unknown function, Adhr, is located about 300 bp 3' to Adh. Although this gene is experiencing a higher rate of synonymous substitution than Adh, it is more constrained at the amino acid level. Phylogenetic relationships between all eight members of the melanogaster subgroup have been analyzed using a variety of methods. All analyses suggested that the D. yakuba and D. teissieri pseudogenes have a single common ancestor, rather than evolving independently in each species, and that D. melanogaster is the sister species to D. simulans, D. sechellia, and D. mauritiana. The evolutionary relationships of the latter three species remain equivocal.      

Involvement of the Reck tumor suppressor protein in maternal and embryonic vascular remodeling in mice

Background

The accessibility of the developing zebrafish pharyngeal dentition makes it an advantageous system in which to study many aspects of tooth development from early initiation to late morphogenesis. In mammals, hedgehog signaling is known to be essential for multiple stages of odontogenesis; however, potential roles for the pathway during initiation of tooth development or in later morphogenesis are incompletely understood.

Results

We have identified mRNA expression of the hedgehog ligands shha and the receptors ptc1 and ptc2 during zebrafish pharyngeal tooth development. We looked for, but did not detect, tooth germ expression of the other known zebrafish hedgehog ligands shhb, dhh, ihha, or ihhb, suggesting that as in mammals, only Shh participates in zebrafish tooth development. Supporting this idea, we found that morphological and gene expression evidence of tooth initiation is eliminated in shha mutant embryos, and that morpholino antisense oligonucleotide knockdown of shha, but not shhb, function prevents mature tooth formation. Hedgehog pathway inhibition with the antagonist compound cyclopamine affected tooth formation at each stage in which we applied it: arresting development at early stages and disrupting mature tooth morphology when applied later. These results suggest that hedgehog signaling is required continuously during odontogenesis. In contrast, over-expression of shha had no effect on the developing dentition, possibly because shha is normally extensively expressed in the zebrafish pharyngeal region.

Conclusion

We have identified previously unknown requirements for hedgehog signaling for early tooth initiation and later morphogenesis. The similarity of our results with data from mouse and other vertebrates suggests that despite gene duplication and changes in the location of where teeth form, the roles of hedgehog signaling in tooth development have been largely conserved during evolution.     

Rationale and design of EXPLORE: a randomized, prospective, multicenter trial investigating the impact of recanalization of a chronic total occlusion on left ventricular function in patients after primary percutaneous coronary intervention for acute ST-elevation myocardial infarction

Background

Hypothyroidism is a prevalent endocrine condition. Individuals with this disease are commonly managed through supplementation with synthetic thyroid hormone, with the aim of alleviating symptoms and restoring normal thyroid stimulating hormone levels. Generally this management strategy is effective and well tolerated. However, there is research to suggest that a significant proportion of hypothyroid sufferers are being inadequately managed. Furthermore, hypothyroid patients are more likely to have a decreased sense of well-being and more commonly experience constitutional and neuropsychiatric complaints, even with pharmacological intervention. The current management of hypothyroidism follows a biomedical model. Little consideration has been given to a biopsychosocial approach to this condition. Within the chiropractic profession there is growing support for the use of a biopsychosocial-based intervention called Neuro-Emotional Technique (NET) for this population.

Methods/Design

A placebo-controlled, single-blinded, randomised clinical pilot-trial has been designed to assess the influence of Neuro-Emotional Technique on a population with primary overt hypothyroidism. A sample of 102 adults (≥18 years) who meet the inclusion criteria will be randomised to either a treatment group or a placebo group. Each group will receive ten treatments (NET or placebo) over a six week period, and will be monitored for six months. The primary outcome will involve the measurement of depression using the Depression, Anxiety and Stress Scale (DASS). The secondary outcome measures to be used are; serum thyroid stimulating hormone, serum free-thyroxine, serum free-triiodothyronine, serum thyroid peroxidase auto-antibodies, serum thyroglobulin auto-antibodies as well as the measurement of functional health and well-being using the Short-Form-36 Version 2. The emotional states of anxiety and stress will be measured using the DASS. Self-measurement of basal heart rate and basal temperature will also be included among the secondary outcome measures. The primary and secondary measures will be obtained at commencement, six weeks and six months. Measures of basal heart rate and basal temperature will be obtained daily for the six month trial period, with recording to commence one week prior to the intervention.

Discussion

The study will provide information on the influence of NET when added to existing management regimens in individuals with primary overt hypothyroidism.

Trial Registration

ANZCTR Number: 12607000040460     

Characterization of chaotic dynamics in the human menstrual cycle

Background  

The human menstrual cycle is known to exhibit a significant amount of unexplained variability. This variation is typically dismissed as random fluctuations in an otherwise periodic and predictable system. Given the many delayed nonlinear feedbacks in the multiple levels of the reproductive endocrine system, however, the menstrual cycle can properly be construed as the output of a nonlinear dynamical system, and such a system has the possibility of being in a chaotic trajectory. We hypothesize that this is in fact the case and that it accounts for the observed variability.