Functional studies on the Wilson copper P-Type ATPase and toxic milk mouse mutant

The Wilson protein (WND; ATP7B) is an essential component of copper homeostasis. Mutations in the <i>ATP7Bi> gene result in Wilson disease, which is characterised by hepatotoxicity and neurological disturbances. In this paper, we provide the first direct biochemical evidence that the WND protein functions as a copper-translocating P-type ATPase in mammalian cells. Importantly, we have shown that the mutation of the conserved Met1386 to Val, in the <i>Atp7Bi> for the mouse model of Wilson disease, toxic milk (tx), caused a loss of Cu-translocating activity. These investigations provide strong evidence that the toxic milk mouse is a valid model for Wilson disease and demonstrate a link between the loss of catalytic function of WND and the Wilson disease phenotype.

Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type 1 and type 2 cytokine-mediated inflammatory reactions

Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in <i>Schistosoma mansonii> infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis,  apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining  coordinated gene expression profiles but are also highly effective for molecularly “fingerprinting” diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious  disease pathogenesis.

Cost-efficacy of surgically induced weight loss for the management of type 2 diabetes : a randomized controlled trial

OBJECTIVE -- To determine the within-trial cost-efficacy of surgical therapy relative to conventional therapy for achieving remission of recently diagnosed type 2 diabetes in class I and II obese patients.

RESEARCH DESIGN AND METHODS -- Efficacy results were derived from a 2-year randomized controlled trial. A health sector perspective was adopted, and within-trial intervention costs included gastric banding surgery, mitigation of complications, outpatient medical consultations, medical investigations, pathology, weight loss therapies, and medication. Resource use was measured based on data drawn from a trial database and patient medical records and valued based on private hospital costs and government schedules in 2006 Australian dollars (AUD). An incremental cost-effectiveness analysis was undertaken.

RESULTS -- Mean 2-year intervention costs per patient were 13,400 AUD for surgical therapy and 3,400 AUD for conventional therapy, with laparoscopic adjustable gastric band (LAGB) surgery accounting for 85% of the difference. Outpatient medical consultation costs were three times higher for surgical patients, whereas medication costs were 1.5 times higher for conventional patients. The cost differences were primarily in the first 6 months of the trial. Relative to conventional therapy, the incremental cost-effectiveness ratio for surgical therapy was 16,600 AUD per case of diabetes remitted (currency exchange: 1 AUD = 0.74 USD).

CONCLUSIONS -- Surgical therapy appears to be a cost-effective option for managing type 2 diabetes in class I and II obese patients.

Ribosome-inactivating proteins : current status and biomedical applications

Ribosome-inactivating proteins (RIPs) are mainly present in plants and function to inhibit protein synthesis through the removal of adenine residues from eukaryotic ribosomal RNA (rRNA). They are broadly classified into two groups: type I and type II. Type I RIPs are a diverse family of proteins comprising a single polypeptide chain, whereas type II RIPs are heterodimeric glycoproteins comprising an A-chain (functionally equivalent to a type I RIP) linked via a disulphide bond to a B chain, mediating cell entry. In this review, we describe common type I and type II RIPs, their diverse biological functions, mechanism of cell entry, stability in plasma and antigenicity. We end with a discussion of promising applications for RIPs in biomedicine.

Certificateless ignatures: New schemes and security models

We present a study of security in certificateless signatures. We divide potential adversaries according to their attack power, and for the first time, three new kinds of adversaries are introduced into certificateless signatures. They are Normal Adversary, Strong Adversary and Super Adversary (ordered by their attack power). Combined with the known Type I Adversary and Type II Adversary in certificateless cryptography, we then define the security of certificateless signatures in different attack scenarios. Our new security models, together with others in the literature, provide a clear definition of the security in certificateless signatures. Two concrete schemes with different security levels are also proposed in this paper. The first scheme, which is proven secure (in the random oracle model) against Normal Type I and Super Type II adversaries, has the shortest signature length among all known certificateless signature schemes. The second scheme is secure (in the random oracle model) against Super Type I and Type II adversaries. Compared with another scheme that has a similar security level, our second scheme requires less operational cost but a little longer signature length. Two server-aided verification protocols are also proposed to reduce the verification cost on the verifier.

Research of a new type rectifier and voltage-multiplier piezoelectric energy harvester circuit

Traditional rectifier circuit can convert AC to DC, but some disadvantages can't be avoided, such as small output current, high power consumption, low conversion efficiency. This paper designs a new type of rectifier voltage-multiplier circuit named MR MOS circuit. It uses a low let-through resistance MOS tube to replace the conventional rectifier diode, and adds the voltage-multiplying factor to the synchronous input port. Therefore, it can improve the rectifier effect and increase the output voltage. By the simulation result of Synopsys Saber Platform, it shows that the new type circuit can implement the rectification and voltage-multiplying by the simulating output pulse voltage of nano fiber made in Deakin University as the source of excitation. It can provide the basic theoretical of the piezoelectric energy harvester (PEH) development, and has certain reference significance to the development of piezoelectricity technology. © (2014) Trans Tech Publications.

Impact of cannabis use on long-term remission in bipolar I and schizoaffective disorder

OBJECTIVE: To investigate the impact of regular cannabis use on long-term remission of mood symptoms in bipolar spectrum disorders. METHODS: The 24-month prospective observational study included patients (n=239) with bipolar I disorder and schizoaffective disorder, bipolar type. Participants were classified as regular cannabis users (three times or more per week) or non-users. The primary outcome measure was the achievement of remission on the evaluations during the 24 months. RESULTS: Of the 234 participants for whom data was available, 25 (10.7%) were regular cannabis users, and the group comprised significantly more males than females. In the total population, cannabis use was significantly associated with decreased likelihood of remission during the 24-month follow-up period. Subgroup analyses showed that cannabis use was significantly associated with lower remission rates on the Hamilton Depression Rating Scale in females (n=139) and patients prescribed mood stabilizers alone (n=151), whereas in males (n=95) and patients prescribed olanzapine and/or a mood stabilizer (n=83), cannabis use was significantly associated with lower remission rates on the Young Mania Rating Scale. Remission rates were lowest in the concurrent cannabis and tobacco smoking group (n=22) followed by the tobacco smoking only group (n=97), and the non-smoker group (n=116). The post-hoc analysis revealed that all remission rates were significantly lower in the concurrent cannabis and the tobacco smoking group compared to the non-smoker group. CONCLUSION: Cannabis use negatively affects the long-term clinical outcome in patients with bipolar spectrum disorders. A comprehensive assessment and integrated management of cannabis use are required to achieve better treatment outcomes for bipolar spectrum disorders.

Mortality trends among people with type 1 and type 2 diabetes in Australia: 1997-2010

OBJECTIVE: With improvements in cardiovascular disease (CVD) rates among people with diabetes, mortality rates may also be changing. However, these trends may be influenced by coding practices of CVD-related deaths on death certificates. We analyzed trends of mortality over 13 years in people with diabetes and quantified the potential misclassification of CVD mortality according to current coding methods. RESEARCH DESIGN AND METHODS: A total of 1,136,617 Australians with diabetes registered on the National Diabetes Services Scheme between 1997 and 2010 were linked to the National Death Index. Excess mortality relative to the Australian population was reported as standardized mortality ratios (SMRs). Potential misclassification of CVD mortality was determined by coding CVD according to underlying cause of death (COD) and then after consideration of both the underlying and other causes listed in part I of the death certificate. RESULTS: For type 1 diabetes, the SMR decreased in males from 4.20 in 1997 to 3.08 in 2010 (Ptrend < 0.001) and from 3.92 to 3.46 in females (Ptrend < 0.01). For type 2 diabetes, the SMR decreased in males from 1.40 to 1.21 (Ptrend < 0.001) and from 1.56 to 1.22 in females (Ptrend < 0.001). CVD deaths decreased from 35.6 to 31.2% and from 31.5 to 27.2% in males and females with type 1 diabetes, respectively (Ptrend < 0.001 for both sexes). For type 2 diabetes, CVD decreased from 44.5 to 29.2% in males and from 45.5 to 31.6% in females (Ptrend < 0.001 for both sexes). Using traditional coding methods, &sim;38 and 26% of CVD deaths are underestimated in type 1 diabetes and type 2 diabetes, respectively. CONCLUSIONS: All-cause and CVD mortality has decreased in diabetes. However, the total CVD mortality burden is underestimated when only underlying COD is considered. This has important ramifications for understanding mortality patterns in diabetes.

Maternal creatine supplementation during pregnancy prevents acute and long-term deficits in skeletal muscle after birth asphyxia: a study of structure and function of hind limb muscle in the spiny mouse

BACKGROUND: Maternal antenatal creatine supplementation protects the brain, kidney, and diaphragm against the effects of birth asphyxia in the spiny mouse. In this study, we examined creatine's potential to prevent damage to axial skeletal muscles.

METHODS: Pregnant spiny mice were fed a control or creatine-supplemented diet from mid-pregnancy, and 1 d before term (39 d), fetuses were delivered by c-section with or without 7.5&thinsp;min of birth asphyxia. At 24&thinsp;h or 33&thinsp;±&thinsp;2 d after birth, gastrocnemius muscles were obtained for <i>ex-vivoi> study of twitch-tension, muscle fatigue, and structural and histochemical analysis.

RESULTS: Birth asphyxia significantly reduced cross-sectional area of all muscle fiber types (<i>Pi> < 0.05), and increased fatigue caused by repeated tetanic contractions at 24&thinsp;h of age (<i>Pi> < 0.05). There were fewer (<i>Pi> < 0.05) Type I and IIa fibers and more (<i>Pi> < 0.05) Type IIb fibers in male gastrocnemius at 33 d of age. Muscle oxidative capacity was reduced (<i>P i>< 0.05) in males at 24&thinsp;h and 33 d and in females at 24&thinsp;h only. Maternal creatine treatment prevented all asphyxia-induced changes in the gastrocnemius, improved motor performance.

CONCLUSION: This study demonstrates that creatine loading before birth protects the muscle from asphyxia-induced damage at birth.