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The highly-conserved Grainyhead-like (Grhl) transcription factors are critical regulators of embryogenesis that regulate cellular survival, proliferation, migration and epithelial integrity, especially during the formation of the craniofacial skeleton. Family member Grhl2 is expressed throughout epithelial tissues during development, and loss of Grhl2 function leads to significant defects in neurulation, abdominal wall closure, formation of the face and fusion of the maxilla/palate. Whereas numerous downstream target genes of Grhl2 have been identified, very little is known about how this crucial developmental transcription factor itself is regulated. Here, using in silico and in utero expression analyses and functional deletion in mice, we have identified a novel 2.4 ​kb enhancer element (mm1286) that drives reporter gene expression in a pattern that strongly recapitulates endogenous Grhl2 in the craniofacial primordia, modulates Grhl2 expression in these tissues, and augments Grhl2-mediated closure of the secondary palate. Deletion of this genomic element, in the context of inactivation of one allele of Grhl2 (through generation of double heterozygous Grhl2+/-;mm1286+/- mice), results in a significant predisposition to palatal clefting at birth. Moreover, we found that a highly conserved 325 bp region of mm1286 is both necessary and sufficient for mediating the craniofacial-specific enhancer activity of this region, and that an extremely well-conserved 12-bp sequence within this element (CTGTCAAACAGGT) substantially determines full enhancer function. Together, these data provide valuable new insights into the upstream genomic regulatory landscape responsible for transcriptional control of Grhl2 during palatal closure.

The highly-conserved Grainyhead-like (Grhl) transcription factors are critical regulators of embryogenesis that regulate cellular survival, proliferation, migration and epithelial integrity, especially during the formation of the craniofacial skeleton. Family member Grhl2 is expressed throughout epithelial tissues during development, and loss of Grhl2 function leads to significant defects in neurulation, abdominal wall closure, formation of the face and fusion of the maxilla/palate. Whereas numerous downstream target genes of Grhl2 have been identified, very little is known about how this crucial developmental transcription factor itself is regulated. Here, using in silico and in utero expression analyses and functional deletion in mice, we have identified a novel 2.4 ​kb enhancer element (mm1286) that drives reporter gene expression in a pattern that strongly recapitulates endogenous Grhl2 in the craniofacial primordia, modulates Grhl2 expression in these tissues, and augments Grhl2-mediated closure of the secondary palate. Deletion of this genomic element, in the context of inactivation of one allele of Grhl2 (through generation of double heterozygous Grhl2+/-;mm1286+/- mice), results in a significant predisposition to palatal clefting at birth. Moreover, we found that a highly conserved 325 bp region of mm1286 is both necessary and sufficient for mediating the craniofacial-specific enhancer activity of this region, and that an extremely well-conserved 12-bp sequence within this element (CTGTCAAACAGGT) substantially determines full enhancer function. Together, these data provide valuable new insights into the upstream genomic regulatory landscape responsible for transcriptional control of Grhl2 during palatal closure.

Peter J. Anderson and Bernadette Atkinson teach Indigenous and Traditionally Education in a Global World as a fourth year unit in the Faculty of Education at Monash University, Clayton. This paper is a self reflective piece of work where they discuss the use of graduate attributes relating to Indigenous Education, put forward by the Australian Institute of Teaching and School Leadership (AITSL). These standards have the potential to improve pre-service teachers knowledge in relation to Indigenous education, therefore equipping them with the necessary skills and tools required to teach effectively to Indigenous and non-Indigenous students. The focus of this paper pertains specifically to AITSL focus area 2.4 Understand and respect Aboriginal and Torres Strait Islander people to promote reconciliation between Indigenous and non- Indigenous Australians discussing how pre-service teachers can promote reconciliation and teach Indigenous subject matter in a respectful manner to non-Indigenous students.

Defective tissue fusion during mammalian embryogenesis results in congenital anomalies, such as exencephaly, spina bifida and cleft lip and/or palate. The highly conserved transcription factor grainyhead-like 2 (Grhl2) is a crucial regulator of tissue fusion, with mouse models lacking GRHL2 function presenting with a fully penetrant open cranial neural tube, facial and abdominal clefting (abdominoschisis), and an open posterior neuropore. Here, we show that GRHL2 interacts with the soluble morphogen protein and bone morphogenetic protein (BMP) inhibitor noggin (NOG) to impact tissue fusion during development. The maxillary prominence epithelium in embryos lacking Grhl2 shows substantial morphological abnormalities and significant upregulation of NOG expression, together with aberrantly distributed pSMAD5-positive cells within the neural crest cell-derived maxillary prominence mesenchyme, indicative of disrupted BMP signalling. Reducing this elevated NOG expression (by generating Grhl2−/−;Nog+/− embryos) results in delayed embryonic lethality, partial tissue fusion rescue, and restoration of tissue form within the craniofacial epithelia. These data suggest that aberrant epithelial maintenance, partially regulated by noggin-mediated regulation of BMP-SMAD pathways, may underpin tissue fusion defects in Grhl2−/− mice. [ABSTRACT FROM AUTHOR]

The health and wellbeing of Australian Indigenous peoples is a nationally sanctioned priority, but despite this, few studies have comprehensively analyzed the features and characteristics of the research in the field. In this regard, a comprehensive scientometric analysis and knowledge mapping to systematically summarize and discuss the current state of research, research trends, and emerging areas of research were conducted. Original articles and reviews published between 2003 and 2022 were obtained from the Web of Science Core Collection. CiteSpace and VOSviewer software were used to perform scientometric analysis and knowledge mapping. An examination of document and citation trends, authors, institutions, countries/regions, journals, and keywords was untaken, while co-citation, cooccurrence, and burst analysis provide insights and future development in this area. A total of 2,468 documents in this field were retrieved. A gradual increase in the number of documents over the past two decades is observed, with the number of documents doubling every ~7.5 years. Author Thompson SC and Charles Darwin University published the most documents, and 85.6% were affiliated with only Australian-based researchers. The Australian and New Zealand Journal of Public Health is the most prominent journal publishing in the field. The most commonly co-occurring keyword was "health," and the keyword "risk" had the longest citation burst. Five keyword clusters were identified; "cultural safety" was the largest. This study articulates the knowledge structure of the research, revealing a shift from population-level and data-driven studies to more applied research that informs Indigenous peoples health and wellbeing. Based on this review, we anticipate emergent research areas to (1) reflect a more comprehensive understanding of the multidimensional factors that shape Indigenous health and wellbeing; (2) move beyond a deficit-based perspective; (3) respect cultural protocols and protect the rights and privacy of Indigenous participants; (4) address racism and discrimination within the healthcare system; (5) foster respectful, equitable, and collaborative research practices with Indigenous peoples; (6) provide culturally appropriate and effective interventions for prevention, early intervention, and treatment; and (7) ensure equitable change in systems to enhance access, quality, and outcomes in health and wellbeing. [ABSTRACT FROM AUTHOR]

Aim: To examine the relationship between motor performance and attention in children born very preterm and at term, and investigate the presence of individual profiles of motor and attention performance. Method: Attention and motor performance at 7 and 13 years were assessed in 197 children born very preterm (52.5% male) and 69 children born at term (47.8% male) between 2001 and 2003. Linear regression models were fitted including an interaction term for birth group. Subgroups of children with similar attention and motor performance profiles were identified using latent profile analysis. Results: Balance was positively associated with all attention outcomes at both ages (p < 0.006). There were specific birth group interactions for aiming and catching and manual dexterity with attention at 13 years, with positive associations observed only for children born very preterm (p < 0.001). At 7 years, three profiles were observed: average attention and motor functioning; average motor functioning and low attention functioning; and low attention and motor functioning. At 13 years, two profiles of average attention and motor functioning emerged, as well as one profile of below-average attention and motor functioning. Children born very preterm were overrepresented in the lower functioning profiles (born very preterm 56%; born at term 29%). Interpretation: Motor functioning at age 7 years may be a useful marker of later attention skills, particularly for children born very preterm who are at greater risk of poorer long-term cognitive outcomes. [ABSTRACT FROM AUTHOR]

Aim: Systemic postnatal corticosteroids are used to treat or prevent bronchopulmonary dysplasia (BPD) in extremely preterm (EP) or extremely low birth weight (ELBW) infants but are associated with long‐term harm. We aimed to assess the relationship between cumulative postnatal corticosteroid dose and neurodevelopmental outcomes. Methods: Longitudinal cohort study of all EP/ELBW livebirths in Victoria, Australia 2016–2017. Perinatal data were collected prospectively. Neurodevelopmental assessment was performed at 2 years' corrected age. Linear and logistic regression were used to determine relationships between cumulative corticosteroid dose and neurodevelopment, adjusted for gestational age, birth weight, sex and major intraventricular haemorrhage. Results: Seventy‐six EP/ELBW infants received postnatal corticosteroids to treat or prevent BPD, 62/65 survivors were seen at 2 years. Median (IQR) cumulative postnatal corticosteroid dose was 1.36 (0.92–3.45) mg/kg dexamethasone equivalent. Higher cumulative corticosteroid dose was associated with increased odds of cerebral palsy, adjusted OR (95% CI) 1.47 (1.04, 2.07). Higher cumulative corticosteroid dose was also associated with lower cognitive and motor developmental scores, however, this weakened after adjustment for confounding variables: cognitive composite score adjusted coefficient (95% CI) −1.3 (−2.7, 0.1) and motor composite score adjusted coefficient (95% CI) −1.3 (−2.8, 0.2). Conclusion: Higher cumulative postnatal corticosteroid dose in EP/ELBW infants is associated with increased odds of cerebral palsy at 2 years' corrected age. Adequately powered studies are needed to assess the independent effects of cumulative steroid dose on neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Children born preterm exhibit working memory deficits. These deficits may be associated with structural brain changes observed in the neonatal period. In this study, the relationship between neonatal regional brain volumes and working memory deficits at age 2 years were investigated, with a particular interest in the dorsolateral prefrontal cortex, parietal cortex and the hippocampus. While the eligible sample consisted of 227 very preterm children who were born at the Royal Women's Hospital, Melbourne prior to 30 weeks gestation or weighing less than 1250 g, 156 children had complete data sets. Neonatal magnetic resonance images of the brain were obtained at term equivalent age and subsequently parcellated into eight sub-regions, while the hippocampus was manually segmented. The relationship between brain volumes for these regions and performance on a working memory task (delayed alternation) at 2 years of age was examined. Very preterm children who perseverated on the working memory task had significantly smaller hippocampal volumes than very preterm children who exhibited intact working memory, even after adjusting for relevant perinatal, sociodemographic and developmental factors. Preterm children appear to have altered hippocampal volumes by discharge from hospital which may have a lasting impact on working memory function.