Pathogens penetrating the central nervous system: Infection pathways and the cellular and molecular mechanisms of invasion

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

Schizophrenia Genetic Variants are not Associated with Intelligence

Background Schizophrenia is associated with lower pre-morbid intelligence (IQ) in addition to (pre-morbid) cognitive decline. Both schizophrenia and IQ are highly heritable traits. Therefore, we hypothesized that genetic variants associated with schizophrenia, including copy number variants (CNVs) and a polygenic schizophrenia (risk) score (PSS), may influence intelligence. Method IQ was estimated with the Wechsler Adult Intelligence Scale (WAIS). CNVs were determined from single nucleotide polymorphism (SNP) data using the QuantiSNP and PennCNV algorithms. For the PSS, odds ratios for genome-wide SNP data were calculated in a sample collected by the Psychiatric Genome-Wide Association Study (GWAS) Consortium (8690 schizophrenia patients and 11 831 controls). These were used to calculate individual PSSs in our independent sample of 350 schizophrenia patients and 322 healthy controls. Results Although significantly more genes were disrupted by deletions in schizophrenia patients compared to controls (p = 0.009), there was no effect of CNV measures on IQ. The PSS was associated with disease status (R 2 = 0.055, p = 2.1 × 10 -7) and with IQ in the entire sample (R 2 = 0.018, p = 0.0008) but the effect on IQ disappeared after correction for disease status. Conclusions Our data suggest that rare and common schizophrenia-associated variants do not explain the variation in IQ in healthy subjects or in schizophrenia patients. Thus, reductions in IQ in schizophrenia patients may be secondary to other processes related to schizophrenia risk. © Cambridge University Press 2013.

Genome-wide association analysis identifies 13 new risk loci for schizophrenia

Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-Analysis with previous schizophrenia GWAS (8,832 cases and 12,067 controls) and finally by replication of SNPs in 168 genomic regions in independent samples (7,413 cases, 19,762 controls and 581 parent-offspring trios). We identified 22 loci associated at genome-wide significance; 13 of these are new, and 1 was previously implicated in bipolar disorder. Examination of candidate genes at these loci suggests the involvement of neuronal calcium signaling. We estimate that 8,300 independent, mostly common SNPs (95% credible interval of 6,300-10,200 SNPs) contribute to risk for schizophrenia and that these collectively account for at least 32% of the variance in liability. Common genetic variation has an important role in the etiology of schizophrenia, and larger studies will allow more detailed understanding of this disorder.

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10 -11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9).

Toxoplasmosis in Indo-Pacific humpbacked dolphins (Sousa chinensis) from Queensland

Objective: To describe the clinical signs, gross pathology, serology, bacteriology, histopathology, electron microscopy and immunohistochemistry findings associated with toxoplasmosis in four Indo-Pacific humpbacked dolphins (Sousa chinensis) that stranded in Queensland in 2000 and 2001. Design: Clinical assessment, gross necropsy, and laboratory examinations. Procedure: Necropsies were performed on four S chinensis to determine cause of death. Laboratory tests including serology, bacteriology, histopathology and transmission electron microscopy were done on the four dolphins. lmmunohistochemistry was done on the brain, heart, liver, lung, spleen and adrenal gland from various dolphins to detect Toxoplasma gondii antigens. Results: Necropsies showed all of four S chinensis that stranded in Queensland in 2000 and 2001 had evidence of predatory shark attack and three were extremely emaciated. Histopathological examinations showed all four dolphins had toxoplasmosis with tissue cysts resembling T gondii in the brain. Tachyzoite stages of T gondii were detected in the lungs, heart, liver, spleen and adrenal gland, variously of all four dolphins. Electron microscopy studies and immunohistochemistry confirmed the tissues cysts were those of Tgondii. All four dolphins also had intercurrent disease including pneumonia, three had peritonitis and one had pancreatitis. Conclusion: Four S chinensis necropsied in Queensland in 2000 and 2001 were found to be infected with toxoplasmosis. It is uncertain how these dolphins became infected and further studies are needed to determine how S chinensis acquire toxoplasmosis. All four dolphins stranded after periods of heavy rainfall, and coastal freshwater runoff may be a risk factor for T gondii infection in S chinensis. This disease should be of concern to wildlife managers since S chinensis is a rare species and its numbers appear to be declining.

Internationalizing school curriculum in Australasia: As niche, by test, or at heart?

Global citizenship has emerged as a pressing curricular priority which all educational systems are currently grappling with. The challenge is to negotiate how this orientation might sit alongside the more traditional mission of mass school curriculum in building collective ballast for a national identity through a common morality and shared narratives, or may conflict with efforts to protect and promote indigenous and minority identities. As a case study of how these agendas interact, this chapter will consider curricular responses to global imperatives in the variegated conditions across the Australasian region (defined as Australia, New Zealand and Papua New Guinea). The chapter will outline recent developments in the social, economic and political contexts surrounding curricular reforms in these settings, and demonstrate how these developments have changed the conditions of possibility and strength of purpose behind efforts to internationalise school curricula. Three types of systemic responses are then described: firstly, an appetite for globally branded curricula such as the International Baccalaureate, Montessori, and Cambridge University Certificates to distinguish some in a stratified market; secondly, convergence in curriculum to improve national performance on international standardised tests; and thirdly, the infusion of cosmopolitan sensibilities, regional identities and intercultural competencies as a core curricular goal for all. The chapter considers the various pragmatic interpretations of ‘internationalisation’ in these responses, and argues that the third response seems both the most difficult to enact, and the most vulnerable to political interference.

Proposed vehicle impact speed: Severe injury probability relationships for selected crash types

Speed is recognised as a key contributor to crash likelihood and severity, and to road safety performance in general. Its fundamental role has been recognised by making Safe Speeds one of the four pillars of the Safe System. In this context, impact speeds above which humans are likely to sustain fatal injuries have been accepted as a reference in many Safe System infrastructure policy and planning discussions. To date, there have been no proposed relationships for impact speeds above which humans are likely to sustain fatal or serious (severe) injury, a more relevant Safe System measure. A research project on Safe System intersection design required a critical review of published literature on the relationship between impact speed and probability of injury. This has led to a number of questions being raised about the origins, accuracy and appropriateness of the currently accepted impact speed–fatality probability relationships (Wramborg 2005) in many policy documents. The literature review identified alternative, more recent and more precise relationships derived from the US crash reconstruction databases (NASS/CDS). The paper proposes for discussion a set of alternative relationships between vehicle impact speed and probability of MAIS3+ (fatal and serious) injury for selected common crash types. Proposed Safe System critical impact speed values are also proposed for use in road infrastructure assessment. The paper presents the methodology and assumptions used in developing these relationships. It identifies further research needed to confirm and refine these relationships. Such relationships would form valuable inputs into future road safety policies in Australia and New Zealand.

Effect of surface-applied treatments on the above-ground performance of simulated timber joinery

We examined the effect of surface-applied treatments on the above-ground decay resistance of the tenon of mortice-and-tenon timber joints designed to simulate joinery that is exposed to the weather. Joints made from untreated radiata pine, Douglas-fir, brush box, spotted gum and copper-chrome-arsenic (CCA) treated radiata pine were exposed to the weather for 9 y on above-ground racks at five sites throughout eastern Australia. Results indicate (1) a poorly maintained external paint film generally accelerated decay, (2) a brush coat of water-repellent preservative inside the joints often extended serviceability (in some cases by a factor of up to seven times that of untreated joints) and (3) the level of protection provided by a coat of primer applied inside the joint varied and in most cases was not as effective as the water-repellent preservative treatment.

Impaired physical function associated with childhood obesity: How should we intervene?

- Background This study examined relationships between adiposity, physical functioning and physical activity. - Methods Obese (N=107) and healthy-weight (N=132) children aged 10-13 years underwent assessments of percent body fat (%BF, dual energy X-ray absorptiometry), knee extensor strength (KE, isokinetic dynamometry), cardiorespiratory fitness (CRF, peak oxygen uptake by cycle ergometry), physical health-related quality of life (HRQOL), worst pain intensity and walking capacity [six-minute walk (6MWT)]. Structural equation modelling was used to assess relationships between variables. - Results Moderate relationships were observed between %BF and 6MWT, KE strength corrected for mass and CRF relative to mass (r -.36 to -.69, P≤.007). Weak relationships were found between: %BF and physical HRQOL (r -.27, P=.008); CRF relative to mass and physical HRQOL (r -.24, P=.003); physical activity and 6MWT (r .17, P=.004). Squared multiple correlations showed that 29.6% variance in physical HRQOL was explained by %BF, pain and CRF relative to mass, while 28% variance in 6MWT was explained by %BF and physical activity. - Conclusions It appears that children with a higher body fat percentage have poorer KE strength, CRF and overall physical functioning. Reducing percent fat appears to be the best target to improve functioning. However, a combined approach to intervention, targeting reductions in body fat percentage, pain and improvements in physical activity and CRF may assist physical functioning.

The efficacy of a vitamin D3 metabolite for improving the myofibrillar tenderness of meat from Bos indicus cattle

The influence of a once only administration of a metabolite of vitamin D3 (HY [middle dot] D(R)-25-hydroxy vitamin D3) on myofibrillar meat tenderness in Australian Brahman cattle was studied. Ninety-six Brahman steers of three phenotypes (Indo-Brazil, US and US/European) and with two previous hormonal growth promotant (HGP) histories (implanted or not implanted with Compudose(R)) were fed a standard feedlot ration for 70 d. Treatment groups of 24 steers were offered daily 10 g/head HY [middle dot] D(R) (125 mg 25-hydroxyvitamin D3) for 6, 4, or 2 d before slaughter. One other group of 24 steers was given the basal diet without HY [middle dot] D(R). Feed lot performance, blood and muscle samples and carcass quality data were collected at slaughter. Calcium, magnesium, potassium, sodium, iron and Vitamin D3 metabolites were measured in plasma and longissimus dorsi muscle. Warner-Bratzler (WB) shear force (peak force, initial yield) and other objective meat quality measurements were made on the longissimus dorsi muscle of each steer after ageing for 1, 7 and 14 d post-mortem at 0-2 [deg]C.There were no significant effects of HY [middle dot] D(R) supplements on average daily gain (ADG, 1.28-1.45 kg/d) over the experimental period. HY [middle dot] D(R) supplements given 6 d prior to slaughter resulted in significantly higher (P (R)) by phenotype/HGP interaction for peak force (P = 0.028), in which Indo-Brazil steers without previous HGP treatment responded positively (increased tenderness) to HY [middle dot] D(R) supplements at 2 d when compared with Indo-Brazil steers previously given HGP. There were no significant effects of treatment on other phenotypes. HY [middle dot] D(R) supplements did not affect muscle or plasma concentrations of calcium, potassium or sodium, but did significantly decrease plasma magnesium and iron concentrations when given 2 d before slaughter. There were no detectable amounts of 25-hydroxyvitamin D3 in the blood or muscle of any cattle at slaughter.

Effects of electrical muscle stimulation on oxygen consumption

Electrical muscle stimulation (EMS) devices are being marketed as weight/ fat loss devices throughout the world. Commercially available stimulators have the ability to evoke muscle contractions that may affect caloric expenditure while the device is being used. The aim of this study was to test the effects of two different EMS devices (Abtronic and Feminique) on oxygen consumption at rest. Subjects arrived for testing after an overnight fast, had the devices fitted, and then positioned supine with expired air measured to determine oxygen consumption. After a 10-minute acclimation period, oxygen consumption was measured for 20 minutes with the device switched off (resting) then 20 minutes with the device switched on (stimulated). There were no significant differences (p > 0.05) in oxygen consumption between the resting and stimulated periods with either the Abtronic (mean +/- SD; resting, 3.40 +/- 0.44; stimulated, 3.45 +/- 0.53 ml of O2[middle dot]kg-1[middle dot]min-1) or the Feminique (resting, 3.73 +/- 0.45; stimulated, 3.75 +/- 0.46 ml of O2[middle dot]kg-1[middle dot]min-1). In summary, the EMS devices tested had no effect on oxygen consumption during muscle stimulation.

Digital Commons Introduction

Presentation given on January 19th, 2005 by Jeff Riedel at the Catherwood Library.

Building and Construction Trades Unions: Are They Built to Win?

[Excerpt] The evidence of labor's declining power in the economic and political arenas is increasingly clear. Despite the tenacious efforts of talented leaders over the past ten years, the labor movement has still failed to turn the proverbial cornet. Some labor leaders now believe that a dramatic change in strategic direction may be necessary to revitalize labor's fortunes. The emerging debate about labor's future touches every sector of the movement. The building and construction trades are no exception.

Potential for using through-boring to improve groundline treatment of Australian wood species: A preliminary study.

An aging electricity distribution system and reduced availability of naturally durable tropical hardwoods in Australia will combine in the next decade to produce a major shortage of poles. One approach to mitigating this shortage is to utilize lower durability species and improve the penetration of preservatives into the refractory heartwood by introducing additional pretreatment processes. A potential method for improving preservative penetration in the critical ground-line zone is through-boring. This process, in which holes are drilled through the pole perpendicular to the grain in the ground-line zone, is widely used in the western United States for treatment of Douglas-fir and may be Suitable for many Australian wood species. The potential for improving heartwood penetration in eucalypts with alkaline-copper-quaternary (ACQ) compound was assessed on heartwood specimens from four species (Eucalyptus cloeziana F.Muell., E. grandis W.Hill ex Maiden, E. obliqua L'Her. and E. pellita F.Muell.) and Lophostemon confertus (R.Br.) Peter G.Wilson & J.T.Wateril). Longitudinal ACQ penetration was extremely shallow in L. confertus and only slightly better in E. cloeziana. Longitudinal penetration was good in both E. obliqua and E. pellita, although there was some variation in treatment results with length of pressure period. The results suggest that through-boring might be a reasonable approach for achieving heartwood penetration in some Eucalyptus species, although further studies are required to assess additional treatment schedules and to determine the effects of the process oil flexural properties of the poles.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.