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Abstract In the Cape Fynbos of South Africa, Psoralea pinnata (L.) plants occur naturally in both wetland and welldrained soils and yet effectively fix N2 under the two contrasting conditions. In this study, nodule structure and functioning in P. pinnata plants from the two habitats were evaluated using light and transmission electron microscopy (TEM), as well as the 15N natural abundance technique. The results showed that, structurally, fully developed P. pinnata nodules were spherical in shape with six components (namely, lenticels, periderm, outer cortex, middle cortex, inner cortex, and a central bacteria-infected medulla region). Morphometric analysis revealed 44 and 84 % increase in cell area and volume of wetland nodules compared to those from upland. The percentage area of nodules occupied by the middle cortex in wetland nodules was twice that of upland nodules. As a result, the size of the medulla region in wetland nodules was significantly reduced compared to upland nodules. Additionally, the average area of medulla occupied by intercellular air spaces in wetland nodules was about five times that of upland nodules (about 431 % increase in wetland over upland nodules). TEM data also showed more bacteroids in symbiosomes of upland nodules when compared to wetland nodules. However, isotopic analysis of above-ground plant parts revealed no differences in symbiotic parameters such as N concentration, ∂15N and %Ndfa between wetland and upland P. pinnata plants. These results suggest that, under limiting O2 conditions especially in wetlands, nodules make structural and functional adjustments to meet the O2 demands of N2-fixing bacteroids.

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Introduction: Biomarkers of tuberculosis (TB) diagnosis and treatment response in patients coinfected with human immunodeficiency virus (HIV) are a necessity to ensure early diagnosis and adequate monitoring of TB treatment response. We conducted 3 sub-studies: study 1 was a bioavailability study; study 2 was a PK study in HIV-TB co-infected persons, and study 3 evaluated a WHO-recommended treatment algorithm in TB-HIV co-infected persons. Study 1 and 2 contributed to the study of 2 (NAT2) polymorphisms. Study 1 was leveraged to evaluate Quantiferon Gold in tube (QFT-GIT) and a quality of life instrument as a longitudinal biomarker in smear and culture positive TB-HIV co-infected patients. Study 3 was leveraged to study urine lipoarabinomannan (LAM) as a diagnostic adjunct in smear-negative HIV-infected patients treated for TB. Methods: Blood was collected from participants with HIV-infection only and TB-HIV coinfection for NAT2 polymorphisms at baseline, and for QFT-GIT at baseline, month 3, 6 and 12; a health-related quality-of-life (HRQOL) instrument was applied at the same timepoints to monitor treatment response in Study 1. An additional 40 TB-HIV co-infected participants (Study 2) were included in the analysis for the assessment of NAT2 polymorphisms and its effect on isoniazid plasma levels and hepatotoxicity. Urine was collected from seriously ill HIV-infected patients with confirmed smear-negative presumptive-TB (Study 3) prior to anti-TB treatment and tested using a commercially available LAM-ELISA. Blood and sputum were collected and processed for TB culture. Results: One hundred and twenty participants (100 TB-HIV co-infected and 20 non-TB but HIVinfected) from Study 1 and Study 2 with genotype results and were evaluated. Percentage of metabolisers in each category were: slow 52.5% (63/120), (NAT2*5/*5); intermediate 35.8% (43/120), (NAT2*4/*5 and NAT2*5/12); and rapid 11.7% (14/120), (NAT2*4/*11, NAT2*11/12 and NAT2*12/12). In general, isoniazid area under the concentration curve (AUC)0-∞ and maximum concentration (Cmax) were lower amongst the study 1 compared to study 2 participants. INH and AcINH PK parameters across genotypes were not statistically significantly different within each study. The log AcINH: log INH ratio, calculated as a measure of acetylation at two and four hours post-dose, showed no statistically significant difference between genotypes.

Includes bibliographical references (leaves 33-42). / Aim: Neurological involvement related to HIV-1 infection is well described in the paediatric population and causes significant morbidity and mortality. This study aimed to describe specific neurological and neurobehavioural complications in this population. Method: Children infected with HIV-1 attending infectious diseases clinics were recruited for general and neurological assessments, developmental history screening and categorization of behavioural phenotype using the Aberrant Behaviour Checklist (ABC). Results: Eighty patients were assessed (males - 44/80: females - 36/80) (median age 5 years 1 month; range: 3 months - 12 yrs). Eighteen patients (23%) were not on antiretroviral (ARV) therapy at the time of testing. The Centre for Disease Control (CDC) immune categories of the patients at the time of assessment were: Category 1- n=6/80, Category 2- n=15/80 and Category 3- n=59/80. Thirty-three percent had a history of chronic lung disease, 10% had a history of an opportunistic central nervous system infection and 12.5% had epilepsy. 5 5 Anthropometric measurements identified that 19% of the patients were microcephalic, 17% of the patients were < 60% of their expected weight, 49% were 60-80% of expected weight and 45% were stunted. On neurological assessment 41% of the patients had global pyramidal tract signs, 7% had a hemiparesis, 5% had peripheral neuropathy, 16% had visual impairment, and 6% were hearing impaired. Of those who were screened for developmental deficits (patients < 6years of age) 66% had gross motor delay, 75% had fine motor delay, 70% had language delay and 73% had cognitive delay. Forty one percent had HIV Encephalopathy, 81% of whom a CD4 count < 15% and 48% were < 1year old. On the aberrant behaviour checklist (ABC) scale 24/80 patients had features of hyperactivity and 22/80 patients scored in the mild-moderate range on the lethargy / social withdrawal sub-scale reflecting a correlation with the affective and adjustment disorders. Conclusion: Diverse neurological and neurobehavioural deficits are common in children with HIV-1 infection especially those with CD4 < 15%, not on ARVs, with growth impairment and < 1yr of age. This study demonstrated the extent and spectrum of neurobehavioural and neurological complications in a defined HIV population. It stresses the need for early initiation of ARVs in the planning for future regimens and guidelines.