α,ω-Bis(trichlorostannyl)alkanes: unravelling the hydrolysis pathway to organotin-oxo oligomers

New α,ω-bis(trichlorostannyl)alkanes, Cl₃Sn(CH₂)_nSnCl₃ [n = 3-5, 8], have been synthesized via tin-phenyl bond cleavage reactions on α,ω-bis(triphenylstannyl)alkanes, Ph₃Sn(CH₂)_nSnPh₃ [n = 3-5, 8], using either SnCl₄ or concentrated hydrochloric acid. Some key missing links, (H₂O)Cl₃Sn(CH₂)₃SnCl₃(H₂O) (1a) and (H₂O)₂Cl₃Sn(CH₂)₃SnCl₃(H₂O)₂ (6), in the hydrolysis pathway of organotin trichlorides were identified. Crystal structures of the nonassociated di-tin compounds (H₂O)Cl₃Sn(CH₂)₃SnCl₃(H₂O) (1a) and (H₂O)₂Cl₃Sn(CH₂)₃SnCl₃(H₂O)₂ (6, isolated as the 18-crown-6 cocrystal acetonitrile solvate) as well as the polymeric hydrolysis product [H₂O(OH)Cl₂Sn(CH₂)₃SnCl₂(OH)H₂O·₂H2O]_n (7·2H₂O) are reported.

Nicotine treatment decreases food intake and body weight via a leptin-independent pathway in Psammomys obesus

It has been reported previously that leptin may be involved in nicotine's ability to reduce body weight. Our aim was to investigate whether the anorexic action of nicotine is related to the actions of leptin by utilizing lean leptin-sensitive and obese leptin-resistant Psammomys obesus. Lean and obese P. obesus were assigned to receive nicotine sulphate at 6, 9 or 12 mg/day or saline (control) for 9 days (n = 6-10 in each group), administered using mini-osmotic pumps. Food intake, body weight, plasma leptin concentrations, plasma insulin and blood glucose were measured at baseline and throughout the study period. Nicotine treatment reduced food intake by up to 40% in lean and obese P. obesus. Plasma leptin levels fell significantly only in lean nicotine-treated animals, whereas no changes were observed in obese nicotine-treated animals. However, both lean and obese nicotine-treated animals had similar reductions in body weight. Our results show that nicotine has dramatic effects on food intake and body weight, however, these changes appear to be independent of the leptin signalling pathway.

Copper-dependent iron assimilation pathway in the model photosynthetic eukaryote chlamydomonas reinhardtii

The unicellular green alga Chlamydomonas reinhardtii is a valuable model for studying metal metabolism in a photosynthetic background. A search of the Chlamydomonas expressed sequence tag database led to the identification of several components that form a copper-dependent iron assimilation pathway related to the high-affinity iron uptake pathway defined originally for Saccharomyces cerevisiae. They include a multicopper ferroxidase (encoded by Fox1), an iron permease (encoded by Ftr1), a copper chaperone (encoded by Atx1), and a copper-transporting ATPase. A cDNA, Fer1, encoding ferritin for iron storage also was identified. Expression analysis demonstrated that Fox1 and Ftr1 were coordinately induced by iron deficiency, as were Atx1 and Fer1, although to lesser extents. In addition, Fox1 abundance was regulated at the posttranscriptional level by copper availability. Each component exhibited sequence relationship with its yeast, mammalian, or plant counterparts to various degrees; Atx1 of C. reinhardtii is also functionally related with respect to copper chaperone and antioxidant activities. Fox1 is most highly related to the mammalian homologues hephaestin and ceruloplasmin; its occurrence and pattern of expression in Chlamydomonas indicate, for the first time, a role for copper in iron assimilation in a photosynthetic species. Nevertheless, growth of C. reinhardtii under copper- and iron-limiting conditions showed that, unlike the situation in yeast and mammals, where copper deficiency results in a secondary iron deficiency, copper-deficient Chlamydomonas cells do not exhibit symptoms of iron deficiency. We propose the existence of a copper-independent iron assimilation pathway in this organism.

Straddling the pathway from paediatrician to mainstream health care : transition issues experienced in disability care

Objective: To identify the strengths and limitations of health care and related services provided to young adults with a disability during the period of transition from the care of a paediatrician to the mainstream health system.
Design: A descriptive design was used to address the study objectives.
Setting: Barwon and south-western region of Victoria.
Subjects: Twelve focus group discussions, with young adults with a disability, carers of young adults with a disability and health care service providers. Each focus group involved eight to 10 participants.
Results: The findings revealed a number of problems with the transition period. All participants acknowledged the supportive, coordinating role of the paediatrician. In the absence of this type of role, carers felt they lacked the knowledge and support to manage the adolescent with a disability. Communication problems between all service providers were identified as being problematical. The general lack of continuity of care between providers made it difficult for individuals to negotiate the transition period and increased the burden of care on carers.
Conclusion: There is a need for policy makers to address these transition problems and develop appropriate services that improve the situation for young adults with a disability and their carers.
What is already known: It is well documented that the transition period from paediatrician to adult health care services is problematic for the young adult with a disability and their carer. The difficulties experienced are attributed to poor communication between service providers and a lack of continuity of care.
What does this study add: This study provides insights from a number of different consumer and health care professionals' perspectives. The findings identify service delivery gaps and a need to develop health care services that could assist the young adult with the disability negotiate this transition from the paediatric services to mainstream health care services in rural and regional settings in Victoria.

Cytokine receptor signaling through the Jak-Stat-Socs pathway in disease

The complexity of multicellular organisms is dependent on systems enabling cells to respond to specific stimuli. Cytokines and their receptors are one such system, whose perturbation can lead to a variety of disease states. This review represents an overview of our current understanding of the cytokine receptors, Janus kinases (Jaks), Signal transducers and activators of transcription (Stats) and Suppressors of cytokine signaling (Socs), focussing on their contribution to diseases of an immune or hematologic nature.

Hydrolysis of bis((trimethylsilyl)methyl)tin dihalides. Crystallographic and spectroscopic study of the hydrolysis pathway

The synthesis and characterization by multinuclear NMR spectroscopy of the diorganotin dihalides (Me₃SiCH₂)₂SnX₂ (1, X = Cl; 2, X = Br), the diorganotin dichloride water adduct (Me₃SiCH₂)₂SnCl₂·H₂O (1a), the dimeric tetraorganodistannoxanes [(Me₃SiCH₂)₂(X)SnOSn(Y)(CH₂SiMe₃)₂]₂ (3, X = Y = Cl; 4, X = Br, Y = OH; 5, X = Br, Y = F; 6, X = Y = OH; 8, X = Cl, Y = OH), and the molecular diorganotin oxide cyclo-[(Me₃SiCH₂)₂SnO]₃ (7) are reported. The structures in the solid state of compounds 1a, 3, 6, and 7 were determined by single-crystal X-ray analysis. In toluene solution, the hydroxy-substituted tetraorganodistannoxane 6 is in equilibrium with the diorganotin oxide 7 and water. The eight-membered diorganotin oxide cyclo-[(Me₃SiCH₂)₂SnO]₄ (7a) is proposed to be involved in this equilibrium. On the basis of the results of this and previous works, a general hydrolysis pathway is developed for diorganotin dichlorides containing reasonably bulky substituents.

The Jak-Stat pathway in Hematopoiesis and Disease

This book for the first time comprehensively surveys the research investigating the Jak-Stat pathway and its role in normal blood development as well as its perturbation in disease. It draws on the expertise of world-renowned medical researchers to take the reader from basic biology through to recent therapeutic advances.

Pathway planning and 'becoming somebody' : Exploring the tensions between wellbeing and credentialism with students at (educational) risk

This paper maps the policy shifts around the education and training of youth that frame how schools respond to issues of youth' at risk'. These shifts have occurred with the move from the self managing schools marked by market discourses of competition, autonomy and image management that supplanted earlier discourses of welfare and community, through to recent policies in Victoria arising from the Kirby Review of Post compulsory Education and Public Education, the Next Generation undertaken by the Labor government. These reports, and the policies emerging out of them, are producing new discourses about youth and schooling focusing on wellbeing, learning networks and more systemic support for schools at the same time as there is increased accountability and expectations of schools. Drawing on the school exclusion literature from the U.K, and using Bourdieu's notion of habitus, we examine the findings from a recent study undertaken on the Geelong Pathways Planning project, funded through a Victorian government strategy, to discuss how schools respond to such initiatives. The project explored the ways in which students in the Geelong region understood and worked with the job planning pathways program, and how service providers (schools, community education facilities, job networks etc) coordinated to meet the needs of individual youth. There was a disjuncture in the participating schools between the discourses of care and welfare for students at risk, and the actual practices and policies that ignored or excluded such students. This paper concludes with a discussion of what might be required systemically, in schools and in their relations to other education providers, to build the capacity to respond more effectively to all students.

Lignin production and monolignol pathway gene expression is suppressed by abscisic acid during defence reactions of Arabidopsis

The phytohormone, abscisic acid (ABA) has been shown to influence the outcome of the interactions between various hosts with biotrophic and hemibiotrophic pathogens. Susceptibility to avirulent isolates can be induced by addition of low physiological concentrations of ABA to plants. In contrast, addition of ABA biosynthesis inhibitors induced resistance following challenge of plants by virulent isolates. ABA deficient mutants of Arabidopsis, such as aba1-1, were resistant to virulent isolates of Peronospora parasitica. In interactions of Arabidopsis with avirulent isolates of Pseudomonas syringae pv. tomato, susceptibility was induced following addition of ABA or imposition of drought stress. These results indicate a pivotal, albiet undefined, role for ABA in determining either susceptibility or resistance to pathogen attack. We have found that the production of the cell wall strengthening compound, lignin, is increased during resistant interactions of aba1-1 but suppressed in ABA induced susceptible interactions. Using RT-PCR and microarray analysis we have found down-regulation by ABA of key genes of the phenylpropanoid pathway especially of those genes involved directly in lignin biosynthesis. ABA also down-regulates a number of genes in other functional classes including those involved in defence and cell signalling.

Suppression by abscisic acid of lignin production and monolignol pathway gene expression in interactions of Arabidopsis with oomycete and bacterial pathogens

The phytohormone, abscisic acid (ABA) has been shown to influence the outcome of the interactions between various hosts with biotrophic and hemibiotrophic pathogens. Susceptibility to avirulent isolates can be induced in plants by addition of low physiological concentrations of ABA. In contrast, addition of ABA biosynthesis inhibitors induced resistance following challenge of plants by virulent isolates. ABA deficient mutants of Arabidopsis, such as aba1-1, were resistant to virulent isolates of Peronospora parasitica. In interactions of Arabidopsis with avirulent isolates of Pseudomonas syringae pv. tomato, susceptibility was induced following addition of ABA or imposition of drought stress. These results indicate a pivotal, albiet undefined, role for ABA in determining either susceptibility or resistance to pathogen attack. We have found that the production of the cell wall strengthening compound, lignin, is increased during resistant interactions of aba1-1 but suppressed in ABA-induced susceptible interactions. Using RT-PCR and microarray analysis we have found down-regulation by ABA of key genes of the phenylpropanoid pathway especially of those genes involved directly in lignin biosynthesis. ABA also down-regulates a number of genes in other functional classes including those involved in defence and cell signalling.

Regulation of STARS and its downstream target suggest a novel pathway involved in human skeletal hypertrophy and atrophy

Skeletal muscle atrophy is a severe consequence of ageing, neurological disorders and chronic disease. Identifying the intracellular signalling pathways controlling changes in skeletal muscle size and function is vital for the future development of potential therapeutic interventions. Striated activator of Rho signalling (STARS), an actin-binding protein, has been implicated in rodent cardiac hypertrophy; however its role in human skeletal muscle has not been determined. This study aimed to establish if STARS, as well as its downstream signalling targets, RhoA, myocardin-related transcription factors A and B (MRTF-A/B) and serum response factor (SRF), were increased and decreased respectively, in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. The mRNA levels of the SRF target genes involved in muscle structure, function and growth, such as α-actin, myosin heavy chain IIa (MHCIIa) and insulin-like growth factor-1 (IGF-1), were also measured. Following resistance training, STARS, MRTF-A, MRTF-B, SRF, α-actin, MHCIIa and IGF-1 mRNA, as well as RhoA and nuclear SRF protein levels were all significantly increased by between 1.25- and 3.6-fold. Following the de-training period all measured targets, except for RhoA, which remained elevated, returned to base-line. Our results show that the STARS signalling pathway is responsive to changes in skeletal muscle loading and appears to play a role in both human skeletal muscle hypertrophy and atrophy.

The calcineurin signal transduction pathway is essential for successful muscle regeneration in mdx dystrophic mice

Although mdx mice share the same genetic defect and lack dystrophin expression as in Duchenne muscular dystrophy (DMD), their limb muscles have a high regenerative capacity that ensures a more benign phenotype and essentially normal function. The cellular pathways responsible for this enhanced regenerative capacity are unknown. We tested the hypothesis that the calcineurin signal transduction pathway is essential for the successful regeneration following severe degeneration observed in the limb muscles of young mdx mice (2–4 weeks old) and that inhibition of this pathway using cyclosporine A (CsA) would exacerbate the dystrophic pathology. Eighteen-day-old mdx and C57BL/10 mice were treated with CsA for 16 days. CsA administration severely disrupted muscle regeneration in mdx mice, but had minimal effect in C57BL/10 mice. Muscles from CsA-treated mdx mice had fewer centrally nucleated fibers and extensive collagen, connective tissue, and mononuclear cell infiltration than muscles from vehicle-treated littermates. The deleterious effects of CsA on muscle morphology were accompanied by a 30–35% decrease in maximal force producing capacity. Taken together, these observations indicate that the calcineurin signal transduction pathway is a significant determinant of successful skeletal muscle regeneration in young mdx mice. Up-regulating this pathway may have clinical significance for DMD.