Reviews

The following publications have been reviewed by the mentioned authors;Plastics and the Environment - reviewed by Melanie FasciatoBuild a Clock - reviewed by John DurrellFood: The Manufacturing Process - reviewed by Julia JonesNuffield Design and Technology 11-14 - reviewed by Alison HardyTechnology in Practice - reviewed by Chris SnellA Strateg for Differentiation - reviewed by Mark HudsonStandards for Technological Literacy: Content for the Study of Technology - reviewed by Eddie NormanStaying on at School - reviewed by Melanie Fasciat

"The daily grunt": middle class bias and vested interests in the 'Getting in Early' and 'Why Can't They Read?' reports.

It is a long-standing and commonly held belief in the UK and elsewhere that the use of elite forms of language reflects superior intellect and education. Expert opinion from sociolinguistics, however, contends that such a view is the result of middle-class bias and cannot be scientifically justified. In the 1960s and 1970s,such luminaries as Labov (1969) and Trudgill (1975) were at pains to point out to educationalists, with some success, that this 'deficit 'view of working-class children's communicative competence is not a helpful one. However, a close reading of recent think-tank reports and policy papers on language and literacy teaching in schools reveals that the linguistic deficit hypothesis has resurfaced and is likely to influence present-day educational policy and practice. In this paper I examine in detail the findings, claims and recommendations of the reports and I argue that they are biased, poorly researched and reflect the vested interests of certain specialist groups, such as speech and language therapists and companies who sell literacy materials to schools. I further argue that we need to, once again, inject the debate with the social dimensions of educational failure, and we need to move away from the pathologisation of working-class children's language patterns

Differential effects of mTOR inhibition and dietary ketosis in a mouse model of subacute necrotizing encephalomyelopathy

Genetic mitochondrial diseases are the most frequent cause of inherited metabolic disorders and one of the most prevalent causes of heritable neurological disease. Leigh syndrome is the most common clinical presentation of pediatric mitochondrial disease, typically appearing in the first few years of life, and involving severe multisystem pathologies. Clinical care for Leigh syndrome patients is difficult, complicated by the wide range of symptoms including characteristic progressive CNS lesion, metabolic sequelae, and epileptic seizures, which can be intractable to standard management. While no proven therapies yet exist for the underlying mitochondrial disease, a ketogenic diet has led to some reports of success in managing mitochondrial epilepsies, with ketosis reducing seizure risk and severity. The impact of ketosis on other aspects of disease progression in Leigh syndrome has not been studied, however, and a rigorous study of the impact of ketosis on seizures in mitochondrial disease is lacking. Conversely, preclinical efforts have identified the intracellular nutrient signaling regulator mTOR as a promising therapeutic target, with data suggesting the benefits are mediated by metabolic changes. mTOR inhibition alleviates epilepsies arising from defects in TSC, an mTOR regulator, but the therapeutic potential of mTOR inhibition in seizures related to primary mitochondrial dysfunction is unknown. Given that ketogenic diet is used clinically in the setting of mitochondrial disease, and mTOR inhibition is in clinical trials for intractable pediatric epilepsies of diverse causal origins, a direct experimental assessment of their effects is imperative. Here, we define the impact of dietary ketosis on survival and CNS disease in the Ndufs4(KO) mouse model of Leigh syndrome and the therapeutic potential of both dietary ketosis and mTOR inhibition on seizures in this model. These data provide timely insight into two important clinical interventions

To what extent does a regional dialect and accent impact on the development of reading and writing skills?

The issue of whether a regional accent and/or dialect impact(s) on the development of literacy skills remains current in the UK. For decades the issue has dogged debate about education outcomes, portable skills and employability. The article summarizes research on the topic using systematic review methodology. A scoping review was undertaken with the research question ‘To what extent does a regional dialect and accent impact on the development of reading and writing skills?’. The review covers research relevant to the teaching of 5-16 year olds in England, but also draws on research within Europe, the USA, Australia and the Caribbean. The results suggest that curricula have marginalized language variation; that the impact of regional accent and dialect on writing is relatively minor; that young people are adept at style-shifting between standard and non-standard forms; and that inappropriate pedagogical responses to regional variation can have detrimental effects on children’s educational achievement

Leukocytes mediate disease pathogenesis in the Ndufs4(KO) mouse model of Leigh syndrome

Symmetric, progressive, necrotizing lesions in the brainstem are a defining feature of Leigh syndrome (LS). A mechanistic understanding of the pathogenesis of these lesions has been elusive. Here, we report that leukocyte proliferation is causally involved in the pathogenesis of LS. Depleting leukocytes with a colony-stimulating factor 1 receptor inhibitor disrupted disease progression, including suppression of CNS lesion formation and a substantial extension of survival. Leukocyte depletion rescued diverse symptoms, including seizures, respiratory center function, hyperlactemia, and neurologic sequelae. These data reveal a mechanistic explanation for the beneficial effects of mTOR inhibition. More importantly, these findings dramatically alter our understanding of the pathogenesis of LS, demonstrating that immune involvement is causal in disease. This work has important implications for the mechanisms of mitochondrial disease and may lead to novel therapeutic strategies

ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies

The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide–specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs

Mechanisms underlying neonate-specific metabolic effects of volatile anesthetics

Volatile anesthetics (VAs) are widely used in medicine, but the mechanisms underlying their effects remain ill-defined. Though routine anesthesia is safe in healthy individuals, instances of sensitivity are well documented, and there has been significant concern regarding the impact of VAs on neonatal brain development. Evidence indicates that VAs have multiple targets, with anesthetic and non-anesthetic effects mediated by neuroreceptors, ion channels, and the mitochondrial electron transport chain. Here, we characterize an unexpected metabolic effect of VAs in neonatal mice. Neonatal blood β-hydroxybutarate (β-HB) is rapidly depleted by VAs at concentrations well below those necessary for anesthesia. β-HB in adults, including animals in dietary ketosis, is unaffected. Depletion of β-HB is mediated by citrate accumulation, malonyl-CoA production by acetyl-CoA carboxylase, and inhibition of fatty acid oxidation. Adults show similar significant changes to citrate and malonyl-CoA, but are insensitive to malonyl-CoA, displaying reduced metabolic flexibility compared to younger animals

Solidarity, stance, and class identities

Scholars have explained working-class speakers’ continued use of stigmatised vernaculars as a response to their relative powerlessness in relation to the standard language market. Research has shown how, in the face of this powerlessness, working-class communities turn to group solidarity, and use of the vernacular is seen as part of this more general orientation. As a result, two competing social values—status and solidarity—have featured prominently in discussions around language and class. I expand these discussions using data from a linguistic ethnographic study of children's language in Teesside, England. I argue that meanings related to status and solidarity operate at multiple levels and cannot be taken for granted, and demonstrate that vernacular forms that lack status within the dominant sociolinguistic economy may be used to assert status within local interactional use. I further advance discussion of the ways local vernaculars might be intimately linked to classed subjectivities. (Social class, variation, solidarity, status, stance, indexicality, identity, interaction, ethnography