Detection and Tracking of SARS-CoV-2 Lineages through National Wastewater Surveillance System Pathogen Genomics.

We conducted retrospective analysis of the emergence of the SARS-CoV-2 JN.1 variant in US wastewater during November 2023-July 2024 using Aquascope, a bioinformatics pipeline for the National Wastewater Surveillance System. This study highlights the value of open-source bioinformatics tools in tracking pathogen variants for public health monitoring.

Heterobimetallic Base Pair Programming in Designer 3D DNA Crystals.

Metal-mediated DNA (mmDNA) presents a pathway toward engineering bioinorganic and electronic behavior into DNA devices. Many chemical and biophysical forces drive the programmable chelation of metals between pyrimidine base pairs. Here, we developed a crystallographic method using the three-dimensional (3D) DNA tensegrity triangle motif to capture single- and multi-metal binding modes across granular changes to environmental pH using anomalous scattering.

Metal-Mediated DNA Nanotechnology in 3D: Structural Library by Templated Diffraction.

DNA double helices containing metal-mediated DNA (mmDNA) base pairs are constructed from Ag and Hg ions between pyrimidine:pyrimidine pairs with the promise of nanoelectronics. Rational design of mmDNA nanomaterials is impractical without a complete lexical and structural description. Here, the programmability of structural DNA nanotechnology toward its founding mission of self-assembling a diffraction platform for biomolecular structure determination is explored.

Metal-Mediated DNA Nanotechnology in 3D: Structural Library by Templated Diffraction.

DNA double helices containing metal-mediated DNA (mmDNA) base pairs have been constructed from Ag and Hg ions between pyrimidine:pyrimidine pairs with the promise of nanoelectronics. Rational design of mmDNA nanomaterials has been impractical without a complete lexical and structural description. Here, we explore the programmability of structural DNA nanotechnology toward its founding mission of self-assembling a diffraction platform for biomolecular structure determination.

Development of high-affinity nanobodies specific for Na1.4 and Na1.5 voltage-gated sodium channel isoforms.

Voltage-gated sodium channels, Nas, are responsible for the rapid rise of action potentials in excitable tissues. Na channel mutations have been implicated in several human genetic diseases, such as hypokalemic periodic paralysis, myotonia, and long-QT and Brugada syndromes. Here, we generated high-affinity anti-Na nanobodies (Nbs), Nb17 and Nb82, that recognize the Na1.

How did absentee voting affect the 2020 U.S. election?

The 2020 U.S. election saw a record turnout, saw a huge increase in absentee voting, and brought unified national Democratic control—yet these facts alone do not imply that vote-by-mail increased turnout or benefited Democrats.

Na1.2 EFL domain allosterically enhances Ca binding to sites I and II of WT and pathogenic calmodulin mutants bound to the channel CTD.

Neuronal voltage-gated sodium channel Na1.2 C-terminal domain (CTD) binds calmodulin (CaM) constitutively at its IQ motif. A solution structure (6BUT) and other NMR evidence showed that the CaM N domain (CaM) is structurally independent of the C-domain (CaM) whether CaM is bound to the Na1.

Structural basis of cytoplasmic NaV1.5 and NaV1.4 regulation.

Voltage-gated sodium channels (NaVs) are membrane proteins responsible for the rapid upstroke of the action potential in excitable cells. There are nine human voltage-sensitive NaV1 isoforms that, in addition to their sequence differences, differ in tissue distribution and specific function. This review focuses on isoforms NaV1.

Universal vote-by-mail has no impact on partisan turnout or vote share.

In response to coronavirus disease 2019 (COVID-19), many scholars and policy makers are urging the United States to expand voting-by-mail programs to safeguard the electoral process. What are the effects of vote-by-mail? In this paper, we provide a comprehensive design-based analysis of the effect of universal vote-by-mail-a policy under which every voter is mailed a ballot in advance of the election-on electoral outcomes. We collect data from 1996 to 2018 on all three US states that implemented universal vote-by-mail in a staggered fashion across counties, allowing us to use a difference-in-differences design at the county level to estimate causal effects.

Ca-dependent regulation of sodium channels Na1.4 and Na1.5 is controlled by the post-IQ motif.

Skeletal muscle voltage-gated Na channel (Na1.4) activity is subject to calmodulin (CaM) mediated Ca-dependent inactivation; no such inactivation is observed in the cardiac Na channel (Na1.5).

Bilobal architecture is a requirement for calmodulin signaling to Ca1.3 channels.

Calmodulin (CaM) regulation of voltage-gated calcium (Ca) channels is a powerful Ca feedback mechanism that adjusts Ca influx, affording rich mechanistic insights into Ca decoding. CaM possesses a dual-lobed architecture, a salient feature of the myriad Ca-sensing proteins, where two homologous lobes that recognize similar targets hint at redundant signaling mechanisms. Here, by tethering CaM lobes, we demonstrate that bilobal architecture is obligatory for signaling to Ca channels.

Calcium triggers reversal of calmodulin on nested anti-parallel sites in the IQ motif of the neuronal voltage-dependent sodium channel Na1.2.

Several members of the voltage-gated sodium channel family are regulated by calmodulin (CaM) and ionic calcium. The neuronal voltage-gated sodium channel Na1.2 contains binding sites for both apo (calcium-depleted) and calcium-saturated CaM.

Calmodulin and Ca(2+) control of voltage gated Na(+) channels.

The structures of the cytosolic portion of voltage activated sodium channels (CTNav) in complexes with calmodulin and other effectors in the presence and the absence of calcium provide information about the mechanisms by which these effectors regulate channel activity. The most studied of these complexes, those of Nav1.2 and Nav1.

Regulation of the NaV1.5 cytoplasmic domain by calmodulin.

Voltage-gated sodium channels (Na(v)) underlie the rapid upstroke of action potentials in excitable tissues. Binding of channel-interactive proteins is essential for controlling fast and long-term inactivation. In the structure of the complex of the carboxy-terminal portion of Na(v)1.