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<jats:p>Development of bispecific antibodies to target mutant peptides in cancer</jats:p>

<jats:p> Highlights from the <jats:italic>Science</jats:italic> family of journals </jats:p>

<jats:p>Editors’ selections from the current scientific literature</jats:p>

<jats:p> Whereas DNA viruses are known to be abundant, diverse, and commonly key ecosystem players, RNA viruses are insufficiently studied outside disease settings. In this study, we analyzed ≈28 terabases of Global Ocean RNA sequences to expand Earth’s RNA virus catalogs and their taxonomy, investigate their evolutionary origins, and assess their marine biogeography from pole to pole. Using new approaches to optimize discovery and classification, we identified RNA viruses that necessitate substantive revisions of taxonomy (doubling phyla and adding &gt;50% new classes) and evolutionary understanding. “Species”-rank abundance determination revealed that viruses of the new phyla “ <jats:italic>Taraviricota</jats:italic> ,” a missing link in early RNA virus evolution, and “ <jats:italic>Arctiviricota</jats:italic> ” are widespread and dominant in the oceans. These efforts provide foundational knowledge critical to integrating RNA viruses into ecological and epidemiological models. </jats:p>

<jats:p>Cytokines signal through cell surface receptor dimers to initiate activation of intracellular Janus kinases (JAKs). We report the 3.6-angstrom–resolution cryo–electron microscopy structure of full-length JAK1 complexed with a cytokine receptor intracellular domain Box1 and Box2 regions captured as an activated homodimer bearing the valine→phenylalanine (VF) mutation prevalent in myeloproliferative neoplasms. The seven domains of JAK1 form an extended structural unit, the dimerization of which is mediated by close-packing of the pseudokinase (PK) domains from the monomeric subunits. The oncogenic VF mutation lies within the core of the JAK1 PK interdimer interface, enhancing packing complementarity to facilitate ligand-independent activation. The carboxy-terminal tyrosine kinase domains are poised for transactivation and to phosphorylate the receptor STAT (signal transducer and activator of transcription)–recruiting motifs projecting from the overhanging FERM (four-point-one, ezrin, radixin, moesin)–SH2 (Src homology 2)-domains. Mapping of constitutively active JAK mutants supports a two-step allosteric activation mechanism and reveals opportunities for selective therapeutic targeting of oncogenic JAK signaling.</jats:p>

<jats:p> The mass of the <jats:italic>W</jats:italic> boson, a mediator of the weak force between elementary particles, is tightly constrained by the symmetries of the standard model of particle physics. The Higgs boson was the last missing component of the model. After observation of the Higgs boson, a measurement of the <jats:italic>W</jats:italic> boson mass provides a stringent test of the model. We measure the <jats:italic>W</jats:italic> boson mass, <jats:italic> M <jats:sub>W</jats:sub> </jats:italic> , using data corresponding to 8.8 inverse femtobarns of integrated luminosity collected in proton-antiproton collisions at a 1.96 tera–electron volt center-of-mass energy with the CDF II detector at the Fermilab Tevatron collider. A sample of approximately 4 million <jats:italic>W</jats:italic> boson candidates is used to obtain <jats:bold> <jats:inline-formula> <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" overflow="scroll"> <mml:mrow> <mml:msub> <mml:mi>M</mml:mi> <mml:mi>W</mml:mi> </mml:msub> <mml:mo>=</mml:mo> <mml:mn>80</mml:mn> <mml:mo>,</mml:mo> <mml:mn>433.5</mml:mn> <mml:mo>±</mml:mo> <mml:msub> <mml:mrow> <mml:mn>6.4</mml:mn> </mml:mrow> <mml:mrow> <mml:mtext>stat</mml:mtext> </mml:mrow> </mml:msub> <mml:mo>±</mml:mo> <mml:msub> <mml:mrow> <mml:mn>6.9</mml:mn> </mml:mrow> <mml:mrow> <mml:mtext>syst</mml:mtext> </mml:mrow> </mml:msub> <mml:mo>=</mml:mo> <mml:mn>80</mml:mn> <mml:mo>,</mml:mo> <mml:mn>433.5</mml:mn> <mml:mo>±</mml:mo> <mml:mn>9.4</mml:mn> <mml:mtext> MeV</mml:mtext> <mml:mo>/</mml:mo> <mml:msup> <mml:mi>c</mml:mi> <mml:mn>2</mml:mn> </mml:msup> </mml:mrow> </mml:math> </jats:inline-formula> </jats:bold> , the precision of which exceeds that of all previous measurements combined (stat, statistical uncertainty; syst, systematic uncertainty; MeV, mega–electron volts; <jats:italic>c</jats:italic> , speed of light in a vacuum). This measurement is in significant tension with the standard model expectation. </jats:p>

<jats:p>The in vitro generation of germ cells from pluripotent stem cells (PSCs) can have a substantial effect on future reproductive medicine and animal breeding. A decade ago, in vitro gametogenesis was established in the mouse. However, induction of primordial germ cell–like cells (PGCLCs) to produce gametes has not been achieved in any other species. Here, we demonstrate the induction of functional PGCLCs from rat PSCs. We show that epiblast-like cells in floating aggregates form rat PGCLCs. The gonadal somatic cells support maturation and epigenetic reprogramming of the PGCLCs. When rat PGCLCs are transplanted into the seminiferous tubules of germline-less rats, functional spermatids—that is, those capable of siring viable offspring—are generated. Insights from our rat model will elucidate conserved and divergent mechanisms essential for the broad applicability of in vitro gametogenesis.</jats:p>

<jats:p> Spike architecture influences grain yield in wheat. We report the map-based cloning of a gene determining the number of spikelet nodes per spike in common wheat. The cloned gene is named <jats:italic>TaCOL-B5</jats:italic> and encodes a CONSTANS-like protein that is orthologous to <jats:italic>COL5</jats:italic> in plant species. Constitutive overexpression of the dominant <jats:italic>TaCol-B5</jats:italic> allele but without the region encoding B-boxes in a common wheat cultivar increases the number of spikelet nodes per spike and produces more tillers and spikes, thereby enhancing grain yield in transgenic plants under field conditions. Allelic variation in <jats:italic>TaCOL-B5</jats:italic> results in amino acid substitutions leading to differential protein phosphorylation by the protein kinase <jats:italic>Ta</jats:italic> K4. The <jats:italic>TaCol-B5</jats:italic> allele is present in emmer wheat but is rare in a global collection of modern wheat cultivars. </jats:p>

<jats:p>The topological structure associated with the branch point singularity around an exceptional point (EP) can provide tools for controlling the propagation of light. Through use of graphene-based devices, we demonstrate the emergence of EPs in an electrically controlled interaction between light and a collection of organic molecules in the terahertz regime at room temperature. We show that the intensity and phase of terahertz pulses can be controlled by a gate voltage, which drives the device across the EP. Our electrically tunable system allows reconstruction of the Riemann surface associated with the complex energy landscape and provides topological control of light by tuning the loss imbalance and frequency detuning of interacting modes. Our approach provides a platform for developing topological optoelectronics and studying the manifestations of EP physics in light–matter interactions.</jats:p>

<jats:p>During bone formation, collagen fibrils mineralize with carbonated hydroxyapatite, leading to a hybrid material with excellent properties. Other minerals are also known to nucleate within collagen in vitro. For a series of strontium- and calcium-based minerals, we observed that their precipitation leads to a contraction of collagen fibrils, reaching stresses as large as several megapascals. The magnitude of the stress depends on the type and amount of mineral. Using in-operando synchrotron x-ray scattering, we analyzed the kinetics of mineral deposition. Whereas no contraction occurs when the mineral deposits outside fibrils only, intrafibrillar mineralization generates fibril contraction. This chemomechanical effect occurs with collagen fully immersed in water and generates a mineral-collagen composite with tensile fibers, reminiscent of the principle of reinforced concrete.</jats:p>