Project 8: Precision electron specroscopy to measure the mass of the neutrino

The Project 8 Collaboration is exploring a new technique for the spectroscopy of medium-energy electrons (∼ 1 - 100 keV) with the ultimate goal of measuring the effective mass of the electron antineutrino by the tritium endpoint method. Our method is based on the detection of microwave-frequency cyclotron radiation emitted by magnetically trapped electrons. The immediate goal of Project 8 is to demonstrate the utility of this technique for a tritium endpoint experiment through a high-precision measurement of the conversion electron spectrum of ^(83)mKr . We present concepts for detecting this cyclotron radiation, focusing on a guided wave design currently being implemented in a prototype apparatus at the University of Washington

Single-Electron Detection and Spectroscopy via Relativistic Cyclotron Radiation

It has been understood since 1897 that accelerating charges must emit electromagnetic radiation. Although first derived in 1904, cyclotron radiation from a single electron orbiting in a magnetic field has never been observed directly. We demonstrate single-electron detection in a novel radio-frequency spectrometer. The relativistic shift in the cyclotron frequency permits a precise electron energy measurement. Precise beta electron spectroscopy from gaseous radiation sources is a key technique in modern efforts to measure the neutrino mass via the tritium decay end point, and this work demonstrates a fundamentally new approach to precision beta spectroscopy for future neutrino mass experiments

CRIM1 Complexes with ß-catenin and Cadherins, Stabilizes Cell-Cell Junctions and Is Critical for Neural Morphogenesis

In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1) is a single-pass (type 1) transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using CRIM1 antisense morpholino oligonucleotides resulted in a failure of neural development. The CRIM1 knockdown phenotype was, in some cases, mild and resulted in perturbed neural fold morphogenesis. In severely affected embryos there was a dramatic failure of cell adhesion in the neural plate and complete absence of neural structures subsequently. Investigation of the mechanism of CRIM1 function revealed that it can form complexes with ß-catenin and cadherins, albeit indirectly, via the cytosolic domain. Consistent with this, CRIM1 knockdown resulted in diminished levels of cadherins and ß-catenin in junctional complexes in the neural plate. We conclude that CRIM1 is critical for cell-cell adhesion during neural development because it is required for the function of cadherin-dependent junctions

Regulation of Classical Cadherin Membrane Expression and F-Actin Assembly by Alpha-Catenins, during Xenopus Embryogenesis

Alpha (α)-E-catenin is a component of the cadherin complex, and has long been thought to provide a link between cell surface cadherins and the actin skeleton. More recently, it has also been implicated in mechano-sensing, and in the control of tissue size. Here we use the early Xenopus embryos to explore functional differences between two α-catenin family members, α-E- and α-N-catenin, and their interactions with the different classical cadherins that appear as tissues of the embryo become segregated from each other. We show that they play both cadherin-specific and context-specific roles in the emerging tissues of the embryo. α-E-catenin interacts with both C- and E-cadherin. It is specifically required for junctional localization of C-cadherin, but not of E-cadherin or N-cadherin at the neurula stage. α-N-cadherin interacts only with, and is specifically required for junctional localization of, N-cadherin. In addition, α -E-catenin is essential for normal tissue size control in the non-neural ectoderm, but not in the neural ectoderm or the blastula. We also show context specificity in cadherin/ α-catenin interactions. E-cadherin requires α-E-catenin for junctional localization in some tissues, but not in others, during early development. These specific functional cadherin/alpha-catenin interactions may explain the basis of cadherin specificity of actin assembly and morphogenetic movements seen previously in the neural and non-neural ectoderm

Integrative taxonomy and phylogeography of Colomys and Nilopegamys (Rodentia: Murinae), semi-aquatic mice of Africa, with descriptions of two new species

The semi-aquatic African murine genera Colomys and Nilopegamys are considered monotypic and thought to be closely related to one another. Colomys occurs across forested regions of equatorial Africa, whereas Nilopegamys is known only from the Ethiopian holotype, making it among the rarest mammalian genera in the world – and possibly extinct. Using morphological and genetic data, we reassess the taxonomy of Colomys and Nilopegamys. A multilocus phylogeny with outgroups demonstrates that Nilopegamys is sister to Colomys. In addition, we recognize at least four morphologically diagnosable and genetically distinct species within Colomys: C. eisentrauti (elevated from subspecies and restricted to north-west Cameroon), C. goslingi (with a more restricted range than previously reported) and two new species (one from Liberia and Guinea and one from central and southern Democratic Republic of the Congo and Angola). We also review the status of four other taxa currently recognized within Colomys goslingi (bicolor, denti, goslingi and ruandensis) and demonstrate that these names lack phylogenetic and/or morphological support. Finally, we discuss potential biogeographic barriers that may have played a role in the evolution of Colomys and Nilopegamys, emphasizing the importance of rivers in both facilitating and, possibly, limiting dispersal within these genera.https://academic.oup.com/zoolinneanhj2022Mammal Research InstituteZoology and Entomolog

Extended Analysis of HIV Infection in Cisgender Men and Transgender Women Who Have Sex with Men Receiving Injectable Cabotegravir for HIV Prevention: HPTN 083

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections included 7 with CAB administration within 6 months of the first HIV-positive visit (2 with on-time injections, 3 with ≥1 delayed injection, and 2 who restarted CAB) and 11 with no recent CAB administration. Three cases had integrase strand transfer inhibitor (INSTI) resistance (2 with on-time injections and 1 who restarted CAB). Among 34 CAB infections analyzed to date, diagnosis delays and INSTI resistance were significantly more common in infections with CAB administration within 6 months of the first HIV-positive visit. This report further characterizes HIV infections in persons receiving CAB preexposure prophylaxis and helps define the impact of CAB on the detection of infection and the emergence of INSTI resistance

Allosteric effects in cyclophilin mutants may be explained by changes in nano-microsecond time scale motions

The relationship between molecular motion and catalysis in enzymes is debated. Here, simulations of cyclophilin A and three catalytically-impaired mutants reveal a nanosecond-scale interconversion between active and inactive conformations, orders of magnitude faster than previously suggested