The expression and functional analysis of neurite outgrowth inhibitors in the nervous system of Xenopus laevis

Includes bibliographical references (leaves 115-128).Generally, the factors contributing to success or failure of axon regeneration lie in the intrinsic properties of the injured neurons, as well as the surrounding microenvironment of the transected axon. Mammalian neurons may lack the intrinsic ability to survive after trauma, or to re-express genes required for axonal regrowth. Moreover, several proteins inhibitory to neurite growth, such as Tenascin-R (TN-R) and Nogo-A, have been identified in mammals. These proteins are associated with oligodendrocytes and myelin and are considered major inhibitory components of the CNS environment

Feeding Bottles Usage and the Prevalence of Childhood Allergy and Asthma

This study aimed to examine the association between the length of use of feeding bottles or pacifiers during childhood and the prevalence of respiratory and allergic morbidities. A large-scale questionnaire survey was performed in day care centers and kindergartens (with children's ages ranging from 2 to 7 years) in southern Taiwan, and a total of 14,862 questionnaires completed by parents were finally recruited for data analysis. Effects of using feeding bottles on children's wheezing/asthma (adjusted OR: 1.05, 95% CI 1.00–1.09), allergic rhinitis (adjusted OR: 1.04, 95% CI 1.00–1.08), and eczema (adjusted OR: 1.07, 95% CI 1.01–1.2) were found. Moreover, significant dose-dependent relationships were further established after an adjustment for confounders was performed that included children's ages, gender, gestational age, birth weight, length of breastfeeding, the age when first given infant formula or complementary foods, family history, parental educational levels, and smoking status, as well as the problem of indoor water damage. This study was the first to reveal the potential risk of using plastic consumer products such as feeding bottles on the reported health status of preschool children in Asian countries

Immunity Against Bacterial Infection of the Central Nervous System: An Astrocyte Perspective

Bacterial infection of the central nervous system (CNS) is a severe and life-threatening condition with high mortality, and it may lead to permanent neurological deficits in survivors. Increasing evidence indicates that astrocytes, as the most abundant CNS glial cell population, regulate innate and adaptive immune responses in the CNS under pathological conditions in addition to their role in the maintenance of CNS homeostasis and neuronal function. Following antigen recognition, astrocytes participate in the initiation of innate immune responses, and prompt an adaptive immune response to recruit peripheral immune cells. Investigations have been conducted to understand the immunological role of astrocytes in CNS disease and injury, however, their part in bacterial infections of the CNS has not been fully evaluated. A better understanding will permit the identification of successful therapeutic targets for an improved prognosis and disease outcome

Persistent p55TNFR expression impairs T cell responses during chronic tuberculosis and promotes reactivation

Acknowledgements We thank Lizette Fick for her contribution to histopathology. We thank Faried Abbass for technical support. We thank the support staff of the Division of Immunology and the Research Animal Facility at the University of Cape Town for their contribution to animal care and technical support. The study was supported by the University of Cape Town, National Research Foundation (South Africa), South African Medical Research Council (SAMRC) National Health Laboratory Service (South Africa), The European Union (contract number: 028190), FP6 NEST project N°028190 “TB REACT”. Research carried out within the scope of the Franco/South African Laboratory “TB Immunity” (Associated International Laboratory ‘AIL’).Peer reviewedPublisher PD

Feeding Bottles Usage and the Prevalence of Childhood Allergy and Asthma

This study aimed to examine the association between the length of use of feeding bottles or pacifiers during childhood and the prevalence of respiratory and allergic morbidities. A large-scale questionnaire survey was performed in day care centers and kindergartens (with children's ages ranging from 2 to 7 years) in southern Taiwan, and a total of 14,862 questionnaires completed by parents were finally recruited for data analysis. Effects of using feeding bottles on children's wheezing/asthma (adjusted OR: 1.05, 95% CI 1.00-1.09), allergic rhinitis (adjusted OR: 1.04, 95% CI 1.00-1.08), and eczema (adjusted OR: 1.07, 95% CI 1.01-1.2) were found. Moreover, significant dose-dependent relationships were further established after an adjustment for confounders was performed that included children's ages, gender, gestational age, birth weight, length of breastfeeding, the age when first given infant formula or complementary foods, family history, parental educational levels, and smoking status, as well as the problem of indoor water damage. This study was the first to reveal the potential risk of using plastic consumer products such as feeding bottles on the reported health status of preschool children in Asian countries

Prominent role for T cell-derived Tumour Necrosis Factor for sustained control of Mycobacterium tuberculosis infection

Tumour Necrosis Factor (TNF) is critical for host control of M. tuberculosis, but the relative contribution of TNF from innate and adaptive immune responses during tuberculosis infection is unclear. Myeloid versus T-cell-derived TNF function in tuberculosis was investigated using cell type-specific TNF deletion. Mice deficient for TNF expression in macrophages/neutrophils displayed early, transient susceptibility to M. tuberculosis but recruited activated, TNF-producing CD4+ and CD8+ T-cells and controlled chronic infection. Strikingly, deficient TNF expression in T-cells resulted in early control but susceptibility and eventual mortality during chronic infection with increased pulmonary pathology. TNF inactivation in both myeloid and T-cells rendered mice critically susceptible to infection with a phenotype resembling complete TNF deficient mice, indicating that myeloid and T-cells are the primary TNF sources collaborating for host control of tuberculosis. Thus, while TNF from myeloid cells mediates early immune function, T-cell derived TNF is essential to sustain protection during chronic tuberculosis infection

Reactivation of M. tuberculosis Infection in Trans-Membrane Tumour Necrosis Factor Mice

Of those individuals who are infected with M. tuberculosis, 90% do not develop active disease and represents a large reservoir of M. tuberculosis with the potential for reactivation of infection. Sustained TNF expression is required for containment of persistent infection and TNF neutralization leads to tuberculosis reactivation. In this study, we investigated the contribution of soluble TNF (solTNF) and transmembrane TNF (Tm-TNF) in immune responses generated against reactivating tuberculosis. In a chemotherapy induced tuberculosis reactivation model, mice were challenged by aerosol inhalation infection with low dose M. tuberculosis for three weeks to establish infection followed chemotherapeutic treatment for six weeks, after which therapy was terminated and tuberculosis reactivation investigated. We demonstrate that complete absence of TNF results in host susceptibility to M. tuberculosis reactivation in the presence of established mycobacteria-specific adaptive immunity with mice displaying unrestricted bacilli growth and diffused granuloma structures compared to WT control mice. Interestingly, bacterial re-emergence is contained in Tm-TNF mice during the initial phases of tuberculosis reactivation, indicating that Tm-TNF sustains immune pressure as in WT mice. However, Tm-TNF mice show susceptibility to long term M. tuberculosis reactivation associated with uncontrolled influx of leukocytes in the lungs and reduced IL-12p70, IFNγ and IL-10, enlarged granuloma structures, and failure to contain mycobacterial replication relative to WT mice. In conclusion, we demonstrate that both solTNF and Tm-TNF are required for maintaining immune pressure to contain reactivating M. tuberculosis bacilli even after mycobacteria-specific immunity has been established

TNF-dependent regulation and activation of innate immune cells are essential for host protection against cerebral tuberculosis

BACKGROUND: Tuberculosis (TB) affects one third of the global population, and TB of the central nervous system (CNS-TB) is the most severe form of tuberculosis which often associates with high mortality. The pro-inflammatory cytokine tumour necrosis factor (TNF) plays a critical role in the initial and long-term host immune protection against Mycobacterium tuberculosis (M. tuberculosis) which involves the activation of innate immune cells and structure maintenance of granulomas. However, the contribution of TNF, in particular neuron-derived TNF, in the control of cerebral M. tuberculosis infection and its protective immune responses in the CNS were not clear. METHODS: We generated neuron-specific TNF-deficient (NsTNF / ) mice and compared outcomes of disease against TNF f/f control and global TNF / mice. Mycobacterial burden in brains, lungs and spleens were compared, and cerebral pathology and cellular contributions analysed by microscopy and flow cytometry after M. tuberculosis infection. Activation of innate immune cells was measured by flow cytometry and cell function assessed by cytokine and chemokine quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS: Intracerebral M. tuberculosis infection of TNF / mice rendered animals highly susceptible, accompanied by uncontrolled bacilli replication and eventual mortality. In contrast, NsTNF / mice were resistant to infection and presented with a phenotype similar to that in TNF f/f control mice. Impaired immunity in TNF / mice was associated with altered cytokine and chemokine synthesis in the brain and characterised by a reduced number of activated innate immune cells. Brain pathology reflected enhanced inflammation dominated by neutrophil influx. CONCLUSION: Our data show that neuron-derived TNF has a limited role in immune responses, but overall TNF production is necessary for protective immunity against CNS-TB

Task-Switching Performance Improvements After Tai Chi Chuan Training Are Associated With Greater Prefrontal Activation in Older Adults

Studies have shown that Tai Chi Chuan (TCC) training has benefits on task-switching ability. However, the neural correlates underlying the effects of TCC training on task-switching ability remain unclear. Using task-related functional magnetic resonance imaging (fMRI) with a numerical Stroop paradigm, we investigated changes of prefrontal brain activation and behavioral performance during task-switching before and after TCC training and examined the relationships between changes in brain activation and task-switching behavioral performance. Cognitively normal older adults were randomly assigned to either the TCC or control (CON) group. Over a 12-week period, the TCC group received three 60-min sessions of Yang-style TCC training weekly, whereas the CON group only received one telephone consultation biweekly and did not alter their life style. All participants underwent assessments of physical functions and neuropsychological functions of task-switching, and fMRI scans, before and after the intervention. Twenty-six (TCC, N = 16; CON, N = 10) participants completed the entire experimental procedure. We found significant group by time interaction effects on behavioral and brain activation measures. Specifically, the TCC group showed improved physical function, decreased errors on task-switching performance, and increased left superior frontal activation for Switch > Non-switch contrast from pre- to post-intervention, that were not seen in the CON group. Intriguingly, TCC participants with greater prefrontal activation increases in the switch condition from pre- to post-intervention presented greater reductions in task-switching errors. These findings suggest that TCC training could potentially provide benefits to some, although not all, older adults to enhance the function of their prefrontal activations during task-switching