Upholding heightened expectations of Indigenous children? Parents do, teachers do not

This paper argues that a component of increasing the rate of Aboriginal and Torres Strait Islander children and youths completing their secondary education is having parents and teachers maintain heightened expectations of these children in achieving this goal. To understand this phenomenon, we investigate the importance of, and discrepancies between, primary caregiver and teacher outlooks regarding Indigenous youths completing year 12. For the purpose of this paper, we adopt the term ‘primary caregiver’ in place of parent. This is because the majority (87.7%) of P1s analysed are the biological mothers with the remainder being close female relatives. P2s analysed are all male, 93.3% are biological fathers; remainder are step-fathers or adoptive fathers. This paper uses quantitative data from the Longitudinal Study of Indigenous Children to measure expectations from parents and teachers of Indigenous children. Results suggest that parents maintain exceptionally high expectations of their children, while teacher's expectations significantly decline over the course of Indigenous children's primary and secondary schooling years. We suggest that relationships and communication between parents and teachers, regarding expectations of students, are important to establishing an equilibrium in expectations of children, and that teachers may benefit from further training to address any underlying biases towards Indigenous children

Course of neuropsychological impairment during Natalizumab associated progressive multifocal leukoencephalopathy.

BACKGROUND Progressive multifocal leukoencephalopathy (PML) - an opportunistic infection of the central nervous system with the John Cunningham virus (JCV) - is a side-effect of Natalizumab (NTZ) treatment for relapsing remitting (RR) multiple sclerosis (MS), potentially leading to a substantial increase of physical and also mental disability. Nevertheless, data of neuropsychological impairment during NTZ-PML disease course is missing. OBJECTIVE To evaluate the neuropsychological disease course of NTZ-PML patients and to compare neuropsychological deficits of NTZ-PML patients with two different non-PML MS cohorts. METHODS Neuropsychological examinations of 28 NTZ-PML patients performed during different phases of the disease (I. at PML-diagnosis, II. during immune reconstitution inflammatory syndrome and III. post-IRIS/PML) were retrospectively analyzed and compared to those of NTZ treated RRMS or SPMS patients with and without immunotherapy. RESULTS Compared to controls, NTZ-PML patients performed worse in neuropsychological examinations during all stages of disease mainly affecting visuo-spatial abilitiy and working memory. Furthermore, failure to eliminate the JCV from the central nervous system (CNS) was associated with a progredient decline of cognition, especially working memory. CONCLUSION Working-memory and visuospatial ability are the core neuropsychological deficits of NTZ-PML patients even in long-term-follow-up. Our finding should be implemented in neurorehabilitation strategies

Two different subunits of importin cooperate to recognize nuclear localization signals and bind them to the nuclear envelope

AbstractBackground: Selective protein import into the cell nucleus occurs in two steps: binding to the nuclear envelope, followed by energy-dependent transit through the nuclear pore complex. A 60 kD protein, importin, is essential for the first nuclear import step, and the small G protein Ran/TC4 is essential for the second. We have previously purified the 60 kD importin protein (importin 60) as a single polypeptide.Results We have identified importin 90, a 90 kD second subunit that dissociates from importin 60 during affinity chromatography on nickel (II)–nitrolotriacetic acid–Sepharose, a technique that was originally used to purify importin 60. Partial amino-acid sequencing of Xenopus importin 90 allowed us to clone and sequence its human homologue; the amino-acid sequence of importin 90 is strikingly conserved between the two species. We have also identified a homologous budding yeast sequence from a database entry. Importin 90 potentiates the effects of importin 60 on nuclear protein import, indicating that the importin complex is the physiological unit responsible for import. To assess whether nuclear localization sequences are recognized by cytosolic receptor proteins, a biotin-tagged conjugate of nuclear localization signals linked to bovine serum albumin was allowed to form complexes with cytosolic proteins in Xenopus egg extracts; the complexes were then retrieved with streptavidin–agarose. The pattern of bound proteins was surprisingly simple and showed only two predominant bands: those of the importin complex. We also expressed the human homologue of importin 60, Rch1p, and found that it was able to replace its Xenopus counterpart in a functional assay. We discuss the relationship of importin 60 and importin 90 to other nuclear import factors.Conclusion Importin consists of a 60 and a 90 kD subunit. Together, they constitute a cytosolic receptor for nuclear localization signals that enables import substrates to bind to the nuclear envelope

Neural Correlates of Post-Conventional Moral Reasoning: A Voxel-Based Morphometry Study

Going back to Kohlberg, moral development research affirms that people progress through different stages of moral reasoning as cognitive abilities mature. Individuals at a lower level of moral reasoning judge moral issues mainly based on self-interest (personal interests schema) or based on adherence to laws and rules (maintaining norms schema), whereas individuals at the post-conventional level judge moral issues based on deeper principles and shared ideals. However, the extent to which moral development is reflected in structural brain architecture remains unknown. To investigate this question, we used voxel-based morphometry and examined the brain structure in a sample of 67 Master of Business Administration (MBA) students. Subjects completed the Defining Issues Test (DIT-2) which measures moral development in terms of cognitive schema preference. Results demonstrate that subjects at the post-conventional level of moral reasoning were characterized by increased gray matter volume in the ventromedial prefrontal cortex and subgenual anterior cingulate cortex, compared with subjects at a lower level of moral reasoning. Our findings support an important role for both cognitive and emotional processes in moral reasoning and provide first evidence for individual differences in brain structure according to the stages of moral reasoning first proposed by Kohlberg decades ago

Moral Competence and Brain Connectivity: A Resting-State fMRI Study

Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n = 31 individuals with MC scores in the highest 15% of the population and n = 33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent operation of these networks. Our findings provide novel insights into how individual differences in moral judgment are associated with RSFC in brain circuits related to emotion processing and cognitive control

Dissipation of potassium and proton gradients inhibits mitochondrial hyperpolarization and cytochrome c release during neural apoptosis.

Exposure of rat hippocampal neurons or human D283 medulloblastoma cells to the apoptosis-inducing kinase inhibitor staurosporine induced rapid cytochrome c release from mitochondria and activation of the executioner caspase-3. Measurements of cellular tetramethylrhodamine ethyl ester fluorescence and subsequent simulation of fluorescence changes based on Nernst calculations of fluorescence in the extracellular, cytoplasmic, and mitochondrial compartments revealed that the release of cytochrome c was preceded by mitochondrial hyperpolarization. Overexpression of the anti-apoptotic protein Bcl-xL, but not pharmacological blockade of outward potassium currents, inhibited staurosporine-induced hyperpolarization and apoptosis. Dissipation of mitochondrial potassium and proton gradients by valinomycin or carbonyl cyanide p-trifluoromethoxy-phenylhydrazone also potently inhibited staurosporine-induced hyperpolarization, cytochrome c release, and caspase activation. This effect was not attributable to changes in cellular ATP levels. Prolonged exposure to valinomycin induced significant matrix swelling, and per se also caused release of cytochrome c from mitochondria. In contrast to staurosporine, however, valinomycin-induced cytochrome c release and cell death were not associated with caspase-3 activation and insensitive to Bcl-xL overexpression. Our data suggest two distinct mechanisms for mitochondrial cytochrome c release: (1) active cytochrome c release associated with early mitochondrial hyperpolarization, leading to neuronal apoptosis, and (2) passive cytochrome c release secondary to mitochondrial depolarization and matrix swelling

Fibroblast growth factor homologous factor 1 interacts with NEMO to regulate NF-κB signaling in neurons.

Neuronal survival and plasticity critically depend on constitutive activity of the transcription factor nuclear factor-κB (NF-κB). We here describe a role for a small intracellular fibroblast growth factor homologue, the fibroblast growth factor homologous factor 1 (FHF1/FGF12), in the regulation of NF-κB activity in mature neurons. FHFs have previously been described to control neuronal excitability, and mutations in FHF isoforms give rise to a form of progressive spinocerebellar ataxia. Using a protein-array approach, we identified FHF1b as a novel interactor of the canonical NF-κB modulator IKKγ/NEMO. Co-immunoprecipitation, pull-down and GAL4-reporter experiments, as well as proximity ligation assays, confirmed the interaction of FHF1 and NEMO and demonstrated that a major site of interaction occurred within the axon initial segment. Fhf1 gene silencing strongly activated neuronal NF-κB activity and increased neurite lengths, branching patterns and spine counts in mature cortical neurons. The effects of FHF1 on neuronal NF-κB activity and morphology required the presence of NEMO. Our results imply that FHF1 negatively regulates the constitutive NF-κB activity in neurons

Bmf upregulation through the AMP-activated protein kinase pathway may protect the brain from seizure-induced cell death.

Prolonged seizures (status epilepticus, SE) can cause neuronal death within brain regions such as the hippocampus. This may contribute to impairments in cognitive functioning and trigger or exacerbate epilepsy. Seizure-induced neuronal death is mediated, at least in part, by apoptosis-associated signaling pathways. Indeed, mice lacking certain members of the potently proapoptotic BH3-only subfamily of Bcl-2 proteins are protected against hippocampal damage caused by status epilepticus. The recently identified BH3-only protein Bcl-2-modifying factor (Bmf) normally interacts with the cytoskeleton, but upon certain cellular stresses, such as loss of extracellular matrix adhesion or energy crisis, Bmf relocalizes to mitochondria, where it can promote Bax activation and mitochondrial dysfunction. Although Bmf has been widely reported in the hematopoietic system to exert a proapoptotic effect, no studies have been undertaken in models of neurological disorders. To examine whether Bmf is important for seizure-induced neuronal death, we studied Bmf induction after prolonged seizures induced by intra-amygdala kainic acid (KA) in mice, and examined the effect of Bmf-deficiency on seizures and damage caused by SE. Seizures triggered an early (1-8 h) transcriptional activation and accumulation of Bax in the cell death-susceptible hippocampal CA3 subfield. Bmf mRNA was biphasically upregulated beginning at 1 h after SE and returning to normal by 8 h, while again being found elevated in the hippocampus of epileptic mice. Bmf upregulation was prevented by Compound C, an inhibitor of adenosine monophosphate-activated protein kinase, indicating Bmf expression may be induced in response to bioenergetic stress. Bmf-deficient mice showed normal sensitivity to the convulsant effects of KA, but, surprisingly, displayed significantly more neuronal death in the hippocampal CA1 and CA3 subfields after SE. These are the first studies investigating Bmf in a model of neurologic injury, and suggest that Bmf may protect neurons against seizure-induced neuronal death in vivo

Understanding the impact and tackling the burden of osteoarthritis for Aboriginal and Torres Strait Islander people

Objective The aim of this study was to understand and describe the lived experience of Aboriginal and Torres Strait Islander people with osteoarthritis. Methods Qualitative study guided by cultural security, which ensures that research is conducted in a way that will not compromise the cultural values, beliefs, and expectations of Aboriginal and Torres Strait Islander people. Participants were purposively sampled through the networks of project staff. Research yarns (a cultural form of conversation used as a data gathering tool) were conducted with 25 Aboriginal and Torres Strait Islander adults with self-reported osteoarthritis in Western Australia and Victoria, Australia. Data were analyzed using a framework approach and presented through composite storytelling (hypothetical stories representing an amalgam of participants’ experiences). Results Two composite stories were constructed to reflect themes relating to beliefs and knowledge, impact, coping, and health care experiences. Common beliefs held by participants were that osteoarthritis is caused by previous physically active lifestyles. Many participants feared for their future, increasing disability and needing a wheelchair. Pain associated with osteoarthritis impacted daily activities, sleep, work, family, and social life and cultural activities. Multidimensional impacts were often experienced within complex health or life circumstances and associated with increased anxiety and depression. Most participants reported negative health care experiences, characterized by poor patient–provider communication. Conclusion Our findings highlight that osteoarthritis is a multidimensional issue for Aboriginal and Torres Strait Islander people that permeates all aspects of life and highlights the need for integrated, multidisciplinary care that is culturally informed and individualized to patient need

Post-Conventional Moral Reasoning is Associated With Increased Ventral Striatal Activity at Rest and During Task

People vary considerably in moral reasoning. According to Kohlberg’s theory, individuals who reach the highest level of post-conventional moral reasoning judge moral issues based on deeper principles and shared ideals rather than self-interest or adherence to laws and rules. Recent research has suggested the involvement of the brain’s frontostriatal reward system in moral judgments and prosocial behaviors. However, it remains unknown whether moral reasoning level is associated with differences in reward system function. Here, we combined arterial spin labeling perfusion and blood oxygen level-dependent functional magnetic resonance imaging and measured frontostriatal reward system activity both at rest and during a sequential risky decision making task in a sample of 64 participants at different levels of moral reasoning. Compared to individuals at the pre-conventional and conventional level of moral reasoning, post-conventional individuals showed increased resting cerebral blood flow in the ventral striatum and ventromedial prefrontal cortex. Cerebral blood flow in these brain regions correlated with the degree of post-conventional thinking across groups. Post-conventional individuals also showed greater task-induced activation in the ventral striatum during risky decision making. These findings suggest that high-level post-conventional moral reasoning is associated with increased activity in the brain’s frontostriatal system, regardless of task-dependent or task-independent states