Laminins promote postsynaptic maturation by an autocrine mechanism at the neuromuscular junction

A prominent feature of synaptic maturation at the neuromuscular junction (NMJ) is the topological transformation of the acetylcholine receptor (AChR)-rich postsynaptic membrane from an ovoid plaque into a complex array of branches. We show here that laminins play an autocrine role in promoting this transformation. Laminins containing the α4, α5, and β2 subunits are synthesized by muscle fibers and concentrated in the small portion of the basal lamina that passes through the synaptic cleft at the NMJ. Topological maturation of AChR clusters was delayed in targeted mutant mice lacking laminin α5 and arrested in mutants lacking both α4 and α5. Analysis of chimeric laminins in vivo and of mutant myotubes cultured aneurally demonstrated that the laminins act directly on muscle cells to promote postsynaptic maturation. Immunohistochemical studies in vivo and in vitro along with analysis of targeted mutants provide evidence that laminin-dependent aggregation of dystroglycan in the postsynaptic membrane is a key step in synaptic maturation. Another synaptically concentrated laminin receptor, Bcam, is dispensable. Together with previous studies implicating laminins as organizers of presynaptic differentiation, these results show that laminins coordinate post- with presynaptic maturation

Machine-Learning Enhanced Photometric Analysis of the Extremely Bright GRB 210822A

We present analytical and numerical models of the bright long GRB 210822A at $z=1.736$. The intrinsic extreme brightness exhibited in the optical, which is very similar to other bright GRBs (e.g., GRBs 080319B, 130427A, 160625A 190114C, and 221009A), makes GRB 210822A an ideal case for studying the evolution of this particular kind of GRB. We use optical data from the RATIR instrument starting at $T+315.9$ s, with publicly available optical data from other ground-based observatories, as well as X-ray data from the Swift/X-ray Telescope (XRT) and data from the Swift/Ultraviolet/Optical Telescope (UVOT). The temporal profiles and spectral properties during the late stages align consistently with the conventional forward shock model, complemented by a reverse shock element that dominates optical emissions during the initial phases ($T<300$ s). Furthermore, we observe a break at $T=80000$ s that we interpreted as evidence of a jet break, which constrains the opening angle to be about $\theta_\mathrm{j}=(3-5)$ degrees. Finally, we apply a machine-learning technique to model the multi-wavelength light curve of GRB 210822A using the AFTERGLOWPY library. We estimate the angle of sight $\theta_{obs}=(6.4 \pm 0.1) \times 10^{-1}$ degrees, the energy $E_0= (7.9 \pm 1.6)\times 10^{53}$ ergs, the electron index $p=2.54 \pm 0.10$, the thermal energy fraction in electrons $\epsilon_e=(4.63 \pm 0.91) \times 10^{-5}$ and in the magnetic field $\epsilon_B= (8.66 \pm 1.01) \times 10^{-6}$, the efficiency $\chi = 0.89 \pm 0.01$, and the density of the surrounding medium $n_\mathrm{0} = 0.85 \pm 0.01$.Comment: Submitted to MNRAS, 11 pages, 6 figures. Fixed typo

The Role of Muscle microRNAs in Repairing the Neuromuscular Junction

microRNAs have been implicated in mediating key aspects of skeletal muscle development and responses to diseases and injury. Recently, we demonstrated that a synaptically enriched microRNA, miR-206, functions to promote maintenance and repair of the neuromuscular junction (NMJ); in mutant mice lacking miR-206, reinnervation is impaired following nerve injury and loss of NMJs is accelerated in a mouse model of amyotrophic lateral sclerosis (ALS). Here, we asked whether other microRNAs play similar roles. One attractive candidate is miR-133b because it is in the same transcript that encodes miR-206. Like miR-206, miR-133b is concentrated near NMJs and induced after denervation. In miR-133b null mice, however, NMJ development is unaltered, reinnervation proceeds normally following nerve injury, and disease progression is unaffected in the SOD1(G93A) mouse model of ALS. To determine if miR-206 compensates for the loss of miR-133b, we generated mice lacking both microRNAs. The phenotype of these double mutants resembled that of miR-206 single mutants. Finally, we used conditional mutants of Dicer, an enzyme required for the maturation of most microRNAs, to generate mice in which microRNAs were depleted from skeletal muscle fibers postnatally, thus circumventing a requirement for microRNAs in embryonic muscle development. Reinnervation of muscle fibers following injury was impaired in these mice, but the defect was similar in magnitude to that observed in miR-206 mutants. Together, these results suggest that miR-206 is the major microRNA that regulates repair of the NMJ following nerve injury.National Institutes of Health (U.S.) (NIH grant R01AG032322)National Institute of Neurological Disorders and Stroke (U.S.) (NRSA Postdoctoral Fellowship from NINDS/NIH)Ruth K. Broad Biomedical Research Foundation (Fellowship)McGovern Institute for Brain Research at MIT (Poitras Center for Affective Disorders Research

Brute-Force Mapmaking with Compact Interferometers: A MITEoR Northern Sky Map from 128 MHz to 175 MHz

We present a new method for interferometric imaging that is ideal for the large fields of view and compact arrays common in 21 cm cosmology. We first demonstrate the method with the simulations for two very different low-frequency interferometers, the Murchison Widefield Array and the MIT Epoch of Reionization (MITEoR) experiment. We then apply the method to the MITEoR data set collected in 2013 July to obtain the first northern sky map from 128 to 175 MHz at ∼2° resolution and find an overall spectral index of −2.73 ± 0.11. The success of this imaging method bodes well for upcoming compact redundant low-frequency arrays such as Hydrogen Epoch of Reionization Array. Both the MITEoR interferometric data and the 150 MHz sky map are available at http://space.mit.edu/home/tegmark/omniscope.html.National Science Foundation (U.S.) (AST-0908848)National Science Foundation (U.S.) (AST-1105835)National Science Foundation (U.S.) (AST-1440343

Mapping our universe in 3D with MITEoR

Mapping our universe in 3D by imaging the redshifted 21 cm line from neutral hydrogen has the potential to overtake the cosmic microwave background as our most powerful cosmological probe, because it can map a much larger volume of our Universe, shedding new light on the epoch of reionization, inflation, dark matter, dark energy, and neutrino masses. We report on MITEoR, a pathfinder low-frequency radio interferometer whose goal is to test technologies that greatly reduce the cost of such 3D mapping for a given sensitivity. MITEoR accomplishes this by using massive baseline redundancy both to enable automated precision calibration and to cut the correlator cost scaling from N[superscript 2] to N log N, where N is the number of antennas. The success of MITEoR with its 64 dual-polarization elements bodes well for the more ambitious HERA project, which incorporates many identical or similar technologies using an order of magnitude more antennas, each with dramatically larger collecting area.National Science Foundation (U.S.) (Grant AST-0908848)National Science Foundation (U.S.) (Grant AST-1105835)MIT Kavli Instrumentation FundMassachusetts Institute of Technology. Undergraduate Research Opportunities Progra

Search for exotic resonances decaying into WZ/ZZ in pp collisions at √s=7 TeV

Journal of High Energy Physics 2013.2 (2013): 036 reproduced by permission of Scuola Internazionale Superiore di Studi Avanzati (SISSA)Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAMA search for new exotic particles decaying to the VZ final state is performed, where V is either a W or a Z boson decaying into two overlapping jets and the Z decays into a pair of electrons, muons or neutrinos. The analysis uses a data sample of pp collisions corresponding to an integrated luminosity of 5 fb-1 collected by the CMS experiment at the LHC at √s=7 TeV in 2011. No significant excess is observed in the mass distribution of the VZ candidates compared with the background expectation from standard model processes. Model-dependent upper limits at the 95% confidence level are set on the product of the cross section times the branching fraction of hypothetical particles decaying to the VZ final state as a function of mass. Sequential standard model W′ bosons with masses between 700 and 940 GeV are excluded. In the Randall-Sundrum model for graviton resonances with a coupling parameter of 0.05, masses between 750 and 880 GeV are also exclude

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Nuclear factor-erythroid-2 related transcription factor-1 (Nrf1) is regulated by O-GlcNAc transferase

The Nrf1 (Nuclear factor E2-related factor 1) transcription factor performs a critical role in regulating cellular homeostasis. Using a proteomic approach, we identified Host Cell Factor-1 (HCF1), a co-regulator of transcription, and O-GlcNAc transferase (OGT), the enzyme that mediates protein O-GlcNAcylation, as cellular partners of Nrf1a, an isoform of Nrf1. Nrf1a directly interacts with HCF1 through the HCF1 binding motif (HBM), while interaction with OGT is mediated through HCF1. Overexpression of HCF1 and OGT leads to increased Nrf1a protein stability. Addition of O-GlcNAc decreases ubiquitination and degradation of Nrf1a. Transcriptional activation by Nrf1a is increased by OGT overexpression and treatment with PUGNAc. Together, these data suggest that OGT can act as a regulator of Nrf1a