The Impact of Advocacy Funding on the School Choice Debate

In this brief, the funding sources of school choice advocates and opponents and their potential impact on policy are examined. In addition, the strategies funders use to promote or oppose the school choice movement are explored

NEPC Review: Choice and Education across the States

Choice and Education across the States, published by the Heartland Institute, is an advocacy document that assigns letter grades to states based on the extensiveness of each state&rsquo;s school choice system. The report asserts, based on a faulty use of past research, that an increase in school choice will strengthen accountability and improve student achievement. It awards most states low grades, reflecting a desire for more school choice throughout the nation. But the report does not provide much in the way of useful information; it only offers the argument that states should increase school choice, dressed up with a letter grade for each state.</p

Clinical and genetic characterization of AP4B1-associated SPG47.

The hereditary spastic paraplegias (HSPs) are a heterogeneous group of disorders characterized by degeneration of the corticospinal and spinocerebellar tracts leading to progressive spasticity. One subtype, spastic paraplegia type 47 (SPG47 or HSP-AP4B1), is due to bi-allelic loss-of-function mutations in the AP4B1 gene. AP4B1 is a subunit of the adapter protein complex 4 (AP-4), a heterotetrameric protein complex that regulates the transport of membrane proteins. Since 2011, 11 individuals from six families with AP4B1 mutations have been reported, nine of whom had homozygous mutations and were from consanguineous families. Here we report eight patients with AP4B1-associated SPG47, the majority born to non-consanguineous parents and carrying compound heterozygous mutations. Core clinical features in this cohort and previously published patients include neonatal hypotonia that progresses to spasticity, early onset developmental delay with prominent motor delay and severely impaired or absent speech development, episodes of stereotypic laughter, seizures including frequent febrile seizures, thinning of the corpus callosum, and delayed myelination/white matter loss. Given that some of the features of AP-4 deficiency overlap with those of cerebral palsy, and the discovery of the disorder in non-consanguineous populations, we believe that AP-4 deficiency may be more common than previously appreciated

Maternal autoimmunity and inflammation are associated with childhood tics and obsessive-compulsive disorder: Transcriptomic data show common enriched innate immune pathways.

Although genetic variation is a major risk factor of neurodevelopmental disorders, environmental factors during pregnancy and early life are also important in disease expression. Animal models demonstrate that maternal inflammation causes fetal neuroinflammation and neurodevelopmental deficits, and brain transcriptomics of neurodevelopmental disorders in humans show upregulated differentially expressed genes are enriched in immune pathways. We prospectively recruited 200 sequentially referred children with tic disorders/obsessive-compulsive disorder (OCD), 100 autoimmune neurological controls, and 100 age-matched healthy controls. A structured interview captured the maternal and family history of autoimmune disease and other pro-inflammatory states. Maternal blood and published Tourette brain transcriptomes were analysed for overlapping enriched pathways. Mothers of children with tics/OCD had a higher rate of autoimmune disease compared with mothers of children with autoimmune neurological conditions (p = 0.054), and mothers of healthy controls (p = 0.0004). Autoimmunity was similarly elevated in first- and second-degree maternal relatives of children with tics/OCD (p 0.0001 and p = 0.014 respectively). Other pro-inflammatory states were also more common in mothers of children with tics/OCD than controls (p 0.0001). Upregulated differentially expressed genes in maternal autoimmune disease and Tourette brain transcriptomes were commonly enriched in innate immune processes. Pro-inflammatory states, including autoimmune disease, are more common in the mothers and families of children with tics/OCD. Exploratory transcriptome analysis indicates innate immune signalling may link maternal inflammation and childhood tics/OCD. Targeting inflammation may represent preventative strategies in pregnancy and treatment opportunities for children with neurodevelopmental disorders

Towards broad spectrum activity-based glycosidase probes: synthesis and evaluation of deoxygenated cyclophellitol aziridines

Activity-based protein profiling has emerged as a powerful tool for visualizing glycosidases in complex biological samples. Several configurational cyclophellitol isomers have been shown to display high selectivity as probes for glycosidases processing substrates featuring the same configuration. Here, a set of deoxygenated cyclophellitols are presented which enable inter-class profiling of [small beta]-glucosidases and [small beta]-galactosidases

Synthesis of Broad-Specificity Activity-Based Probes for Exo-β-Mannosidases

Exo-β-mannosidases are a broad class of stereochemically retaining hydrolases that are essential for the breakdown of complex carbohydrate substrates found in all kingdoms of life. Yet the detection of exo-β-mannosidases in complex biological samples remains challenging, necessitating the development of new methodologies. Cyclophellitol and its analogues selectively label the catalytic nucleophiles of retaining glycoside hydrolases, making them valuable tool compounds. Furthermore, cyclophellitol can be readily redesigned to enable the incorporation of a detection tag, generating activity-based probes (ABPs) that can be used to detect and identify specific glycosidases in complex biological samples. Towards the development of ABPs for exo-β-mannosidases, we present a concise synthesis of β-manno-configured cyclophellitol, cyclophellitol aziridine, and N-alkyl cyclophellitol aziridines. We show that these probes covalently label exo-β-mannosidases from GH families 2, 5, and 164. Structural studies of the resulting complexes support a canonical mechanism-based mode of action in which the active site nucleophile attacks the pseudoanomeric centre to form a stable ester linkage, mimicking the glycosyl enzyme intermediate. Furthermore, we demonstrate activity-based protein profiling using an N-alkyl aziridine derivative by specifically labelling MANBA in mouse kidney tissue. Together, these results show that synthetic manno-configured cyclophellitol analogues hold promise for detecting exo-β-mannosidases in biological and biomedical research

Geographical distribution and genetic dversity of the Banana Fusarium Wilt Fungus in Laos and Vietnam

Fusarium wilt, caused by the fungus Fusarium oxysporum f. sp. cubense (Foc), poses a major threat to global banana production. The tropical race 4 (TR4) variant of Foc is a highly virulent form with a large host range, and severely affects Cavendish bananas. Foc TR4 was recently observed within the Greater Mekong Subregion, after Chinese private companies expanded Cavendish pro duction to the region. In this study, extensive surveys conducted across Laos and Vietnam show that Foc TR4 is still mainly constricted to the northern regions of these countries and is limited to Cavendish cultivation settings. In Laos, Foc TR4 is associated with large-scale Cavendish plantations owned by or involved with Chinese companies through which infected planting material could have been imported. In Vietnam, mostly small-holder Cavendish farmers and backyard gardens were affected by Foc TR4. In Vietnam, no direct link is found with Chinese growers, and it is expected the pathogen mainly spreads through local and regional movement of infected planting materials. Foc TR4 was not recorded on banana cultivars other than Cavendish. The extensively cultivated ‘Pisang Awak’ cultivar was solely infected by VCGs belonging to Foc race 1 and 2, with a high occurrence of VCG 0123 across Laos, and of VCG 0124/5 in Vietnam. Substantial diversity of Foc VCGs was recorded (VCGs 0123, 0124/5, 01218 and 01221) from northern to southern regions in both countries, suggesting that Fusarium wilt is well established in the region. Interviews with farmers indicated that the local knowledge of Fusarium wilt epidemiology and options for disease management was limited. Clear communication efforts on disease epidemiology and management with emphasis on biosecurity practices need to be improved in order to prevent further spread of Foc TR4 to mixed variety smallholder settings

Antibody Responses to Two Recombinant Treponemal Antigens (rp17 and TmpA) before and after Azithromycin Treatment for Yaws in Ghana and Papua New Guinea.

WHO and its partners aim to interrupt yaws transmission in countries of endemicity and to certify others as being yaws-free. Transmission can be assessed using rapid plasma reagin (RPR) tests, reflecting current or recent infection, but RPR is operationally impractical. We evaluated changes in antibody levels against two recombinant treponemal antigens, rp17 (also known as Tp17) and TmpA, after antibiotic treatment given as part of a randomized controlled trial for yaws in Ghana and Papua New Guinea. Paired serum samples from children aged 6 to 15?years with confirmed yaws, collected before and after treatment, were tested for antibodies to rp17 and TmpA using a semiquantitative bead-based immunoassay. Of 344 baseline samples, 342 tested positive for anti-rp17 antibodies and 337 tested positive for anti-TmpA antibodies. Six months after treatment, the median decrease in anti-rp17 signal was 3.2%, whereas the median decrease in anti-TmpA was 53.8%. The magnitude of change in the anti-TmpA response increased with increasing RPR titer fold change. These data demonstrate that responses to TmpA decrease markedly within 6?months of treatment whereas (as expected) those to rp17 do not. Incorporating responses to TmpA as a marker of recent infection within an integrated sero-surveillance platform could provide a way to prioritize areas for yaws mapping