•Explores the role of language as a key input into the process of student learning.•Provides causal estimates of mother tongue schooling on indicators of human capital.•Mother tongue instruction ...increases the probability of being able to read an entire sentence by 40%.•It increases completed years of schooling by 0.65years and the probability of completing primary schooling by 5•It increases newspaper readership by 25%.
In 1994, Ethiopia introduced mother tongue instruction in primary schooling for the largest ethnic group in the country. Combining data from before and after the policy change, from the regions that gain access to mother tongue schooling, along with the regions and ethnic groups that face no change in language policy, I estimate the effect of mother tongue instruction on human capital formation. The results show that access to mother tongue schooling increases the ability to read by 40%. Moreover, it increases the completed years of schooling by more than half a year, and the probability of completing primary schooling by five percentage points. The ability to read by permitting access to printed sources of information, increases newspaper readership by around 25% and makes it 17% points more likely that individuals report using pamphlets, posters or leaflets as a source of information about family planning. My preferred interpretation of the results is that provision of schooling in a language spoken at home, and used for social interactions, reduces the cost and increases the efficiency of learning. The result highlights the use of non-native languages, an almost ubiquitous practice in Sub-Saharan Africa, as a potentially important factor underlying the large educational failures in this part of the world.
Müller glia (MG) dedifferentiation into a cycling population of multipotent progenitors is crucial to zebrafish retina regeneration. The mechanisms underlying MG dedifferentiation are unknown. Here ...we report that heparin-binding epidermal-like growth factor (HB-EGF) is rapidly induced in MG residing at the injury site and that pro-HB-EGF ectodomain shedding is necessary for retina regeneration. Remarkably, HB-EGF stimulates the formation of multipotent MG-derived progenitors in the uninjured retina. We show that HB-EGF mediates its effects via an EGFR/MAPK signal transduction cascade that regulates the expression of regeneration-associated genes, like ascl1a and pax6b. We also uncover an HB-EGF/Ascl1a/Notch/hb-egfa-signaling loop that helps define the zone of injury-responsive MG. Finally, we show that HB-EGF acts upstream of the Wnt/β-catenin-signaling cascade that controls progenitor proliferation. These data provide a link between extracellular signaling and regeneration-associated gene expression in the injured retina and suggest strategies for stimulating retina regeneration in mammals.
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► Heparin-binding epidermal-like growth factor (HB-EGF) is induced by retinal injury ► HB-EGF is necessary and sufficient to stimulate Müller glia (MG) dedifferentiation ► HB-EGF/MAPK/ASCL1a/Notch/hb-egfa signaling defines the zone of injury-responsive MG ► HB-EGF regulates progenitor proliferation via a Wnt/β-catenin-signaling pathway
Using zebrafish retina regeneration as a model system, Wan et al. report that Muller glia-derived HB-EGF is necessary and sufficient for stimulating retina regeneration. HB-EGF, acting via the EGFR, stimulates MAPK and Notch signaling pathways that control Muller glia dedifferentiation and redifferentiation into retinal neurons and glia.
Gasdermin D (GSDMD) is an effector molecule for pyroptosis downstream of canonical and noncanonical inflammasome signaling pathways. Cleavage of GSDMD by inflammatory caspases triggers the ...oligomerization and lipid binding by its N-terminal domain, which assembles membrane pores, whereas its C-terminal domain binds the N-terminal domain to inhibit pyroptosis. Despite recent progress in our understanding of the structure and function of the murine gasdermin A3 (mGSDMA3), the molecular mechanisms of GSDMD activation and regulation remain poorly characterized. Here, we report the crystal structures of the full-length murine and human GSDMDs, which reveal the architecture of the GSDMD N-terminal domains and demonstrate distinct and common features of autoinhibition among gasdermin family members utilizing their β1-β2 loops. Disruption of the intramolecular domain interface enhanced pyroptosis, whereas mutations at the predicted lipid-binding or oligomerization surface reduced cytolysis. Our study provides a framework for understanding the autoinhibition, lipid binding, and oligomerization of GSDMD by using overlapping interfaces.
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•The crystal structures of the murine and human GSDMDs are determined•The N- and C-domain association shares features with the murine GSDMA3•Disruption of the lipid-binding or oligomerization surface suppresses cell killing•Overlapping surfaces mediate autoinhibition, lipid binding, and oligomerization
The molecular mechanisms for activation and regulation of gasdermin D (GSDMD) are poorly characterized. Liu et al. report the crystal structures of the full-length murine and human GSDMDs, which reveal distinct and common features of autoinhibition among gasdermin family members, as well as an overlapping surface for lipid binding and oligomerization.
This paper investigates the stability and reliability analysis of a non‐isolated high‐gain DC‐DC converter. The proposed DC‐DC converter produces a high gain output voltage with a lower duty ratio ...and reduced voltage stress on the semiconductor switch. A reliability analysis is performed to predict the failure rate and lifetime of the individual components using the military handbook (MIL‐HDBK‐217F). A state space equation and small signal modeling of the proposed converter are derived to elucidate the performance of the proposed converter through stability analysis. A closed‐loop using PID controller is incorporated to attain the constant regulated output voltage during sudden parameter changes. The validation of the closed‐loop using the PID controller is verified with the wide range of variations in the different parameters, such as input voltage, load value, and reference voltage value. The laboratory‐based prototype is developed for the proposed converter and validated the performance with 250 W. The power density and efficiency of the proposed converter are 1.360 kW/L and 93%, respectively.
Stability analysis is carried out for the proposed converter to examine the feasibility analysis during sudden disturbances. Reliability analysis is carried out to examine the failure rate analysis of the individual components.
Mitochondrial fragmentation and bioenergetic failure manifest in Huntington's disease (HD), a fatal neurodegenerative disease. The factors that couple mitochondrial fusion/fission with bioenergetics ...and their impacts on neurodegeneration however remain poorly understood. Our proteomic analysis identifies mitochondrial protein ATAD3A as an interactor of mitochondrial fission GTPase, Drp1, in HD. Here we show that, in HD, ATAD3A dimerization due to deacetylation at K135 residue is required for Drp1-mediated mitochondrial fragmentation. Disturbance of ATAD3A steady state impairs mtDNA maintenance by disrupting TFAM/mtDNA binding. Blocking Drp1/ATAD3A interaction with a peptide, DA1, abolishes ATAD3A oligomerization, suppresses mitochondrial fragmentation and mtDNA lesion, and reduces bioenergetic deficits and cell death in HD mouse- and patient-derived cells. DA1 treatment reduces behavioral and neuropathological phenotypes in HD transgenic mice. Our findings demonstrate that ATAD3A plays a key role in neurodegeneration by linking Drp1-induced mitochondrial fragmentation to defective mtDNA maintenance, suggesting that DA1 might be useful for developing HD therapeutics.
A high gain nonisolated DC-DC converter using a single power semiconductor switch is proposed in this article. The operation of the proposed converter is explained under continuous conduction mode ...(CCM), discontinuous conduction mode (DCM), and boundary conduction mode (BCM). The mathematical expressions for steady-state voltage gain, voltage stress, and current stress of diodes and switch are provided. Also, the design of inductors and capacitors in the CCM mode is explained with appropriate mathematical equations. The proposed topology is tested with a 200 W prototype at 50 kHz and a 60% duty cycle. The dynamic behavior of the proposed converter is examined by changing the duty cycle value and also load values. The proposed converter is verified with experimental results to prove the effectiveness of its operation. The proposed converter provides higher steady-state voltage gain as compared with recently developed topologies. The efficiency and power density of the proposed converter is 90% and 1.16 kW/L, respectively.
Key to successful retina regeneration in zebrafish are Müller glia (MG) that respond to retinal injury by dedifferentiating into a cycling population of retinal progenitors. Although recent studies ...have identified several genes involved in retina regeneration, the signaling mechanisms underlying injury-dependent MG proliferation have remained elusive. Here we report that canonical Wnt signaling controls the proliferation of MG-derived retinal progenitors. We found that injury-dependent induction of Ascl1a suppressed expression of the Wnt signaling inhibitor, Dkk, and induced expression of the Wnt ligand, Wnt4a. Genetic and pharmacological inhibition of Wnt signaling suppressed injury-dependent proliferation of MG-derived progenitors. Remarkably, in the uninjured retina, glycogen synthase kinase-3β (GSK-3β) inhibition was sufficient to stimulate MG dedifferentiation and the formation of multipotent retinal progenitors that were capable of differentiating into all major retinal cell types. Importantly, Ascl1a expression was found to contribute to the multipotential character of these progenitors. Our data suggest that Wnt signaling and GSK-3β inhibition, in particular, are crucial for successful retina regeneration.
In this brief, a new non-isolated high gain DC-DC converter topology is proposed to attain the high-voltage conversion ratio. The high-voltage conversion ratio is achieved without utilizing the ...coupled inductors and any transformers. The proposed topology utilizes a single power semiconductor switch and its operation is examined under continuous conduction mode (CCM), discontinuous conduction mode (DCM) and boundary conduction mode (BCM). The theoretical analysis and design procedure for passive components are provided with mathematical expressions. The validity of the theoretical analysis is examined by using a laboratory prototype of the proposed converter with a power rating of 200 W. The experimental results are taken under CCM with a 60% duty cycle. The proposed topology is also examined with dynamic changes in duty cycle value and load values. The efficiency and power density of the proposed converter are 90% and 1.03kW/L.
Cardiolipin (CL) is an atypical, dimeric phospholipid essential for mitochondrial dynamics in eukaryotic cells. Dynamin-related protein 1 (Drp1), a cytosolic member of the dynamin superfamily of ...large GTPases, interacts with CL and functions to sustain the balance of mitochondrial division and fusion by catalyzing mitochondrial fission. Although recent studies have indicated a role for CL in stimulating Drp1 self-assembly and GTPase activity at the membrane surface, the mechanism by which CL functions in membrane fission, if at all, remains unclear. Here, using a variety of fluorescence spectroscopic and imaging approaches together with model membranes, we demonstrate that Drp1 and CL function cooperatively in effecting membrane constriction toward fission in three distinct steps. These involve 1) the preferential association of Drp1 with CL localized at a high spatial density in the membrane bilayer, 2) the reorganization of unconstrained, fluid-phase CL molecules in concert with Drp1 self-assembly, and 3) the increased propensity of CL to transition from a lamellar, bilayer arrangement to an inverted hexagonal, nonbilayer configuration in the presence of Drp1 and GTP, resulting in the creation of localized membrane constrictions that are primed for fission. Thus we propose that Drp1 and CL function in concert to catalyze mitochondrial division.
Sorting nexins (SNX) are a family of PX domain-containing proteins with pivotal roles in trafficking and signaling. SNX-BARs, which also have a curvature-generating Bin/Amphiphysin/Rvs (BAR) domain, ...have membrane-remodeling functions, particularly at the endosome. The minimal PX-BAR module is a dimer mediated by BAR-BAR interactions. Many SNX-BAR proteins, however, additionally have low-complexity N-terminal regions of unknown function. Here, we present the cryo-EM structure of the full-length SNX-BAR Mvp1, which is an autoinhibited tetramer. The tetramer is a dimer of dimers, wherein the membrane-interacting BAR surfaces are sequestered and the PX lipid-binding sites are occluded. The N-terminal low-complexity region of Mvp1 is essential for tetramerization. Mvp1 lacking its N-terminus is dimeric and exhibits enhanced membrane association. Membrane binding and remodeling by Mvp1 therefore requires unmasking of the PX and BAR domain lipid-interacting surfaces. This work reveals a tetrameric configuration of a SNX-BAR protein that provides critical insight into SNX-BAR function and regulation.