The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules.

Hantaviruses are lipid-enveloped, tri-segmented RNA viruses belonging to the family Bunyaviridae. Hantaviruses are divided taxonomically into Old World and New World groups that typically cause hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome, respectively. Each hantavirus is specific to a rodent reservoir host. In 1983, isolation of an Old World hantavirus similar to Seoul virus (Tchoupitoulas virus) occurred from rats caught in New Orleans, Louisiana, but to date, this virus has not been associated with human disease. Since that time, no hantavirus surveillance has been conducted in this geographic area. We sought to determine if Old World hantaviruses still circulate in rodents in New Orleans and, if so, to decrease rat populations to reduce the risk of human-rodent interaction and the potential for disease transmission. Over a 3-year period, rodents were live-trapped using Sherman and Tomahawk traps. Blood and other tissues were collected and samples tested for the presence of Old World hantaviruses via Reverse transcriptase Polymerase Chain Reaction. Trap sites were identified through selected citizen service requests and routine municipal rodent management activities. Of the 172 roof rats and Norway rats collected, 3.6% tested positive, indicating continued presence of Old World hantaviruses in New Orleans. This study raised awareness of the continued risk of rodent-borne disease in the greater New Orleans area and spawned proactive management strategies on a city-wide basis, including neighborhood surveys, public education and awareness campaigns, and an aggressive rodenticide baiting program in areas with large rodent populations. Continued surveillance and detection of hantaviruses and other rodent-borne pathogens will help preserve the safety and health of New Orleans residents.

Although substantial progress has been made with Ebola virus (EBOV) vaccine measures, the immune correlates of vaccine-mediated protection remain uncertain. Here, five mucosal vaccine vectors based on human and avian paramyxoviruses provided nonhuman primates with varying degrees of protection, despite expressing the same EBOV glycoprotein (GP) immunogen. Each vaccine produced antibody responses that differed in Fc-mediated functions and isotype composition, as well as in magnitude and coverage toward GP and its conformational and linear epitopes. Differences in the degree of protection and comprehensive characterization of the response afforded the opportunity to identify which features and functions were elevated in survivors and could therefore serve as vaccine correlates of protection. Pairwise network correlation analysis of 139 immune- and vaccine-related parameters was performed to demonstrate relationships with survival. Total GP-specific antibodies, as measured by biolayer interferometry, but not neutralizing IgG or IgA titers, correlated with survival. Fc-mediated functions and the amount of receptor binding domain antibodies were associated with improved survival outcomes, alluding to the protective mechanisms of these vaccines. Therefore, functional qualities of the antibody response, particularly Fc-mediated effects and GP specificity, rather than simply magnitude of the response, appear central to vaccine-induced protection against EBOV. The heterogeneity of the response profile between the vaccines indicates that each vaccine likely exhibits its own protective signature and the requirements for an efficacious EBOV vaccine are complex.

The IceCube Neutrino Observatory instruments about 1ĝ€¯km3 of deep, glacial ice at the geographic South Pole. It uses 5160 photomultipliers to detect Cherenkov light emitted by charged relativistic particles. An unexpected light propagation effect observed by the experiment is an anisotropic attenuation, which is aligned with the local flow direction of the ice. We examine birefringent light propagation through the polycrystalline ice microstructure as a possible explanation for this effect. The predictions of a first-principles model developed for this purpose, in particular curved light trajectories resulting from asymmetric diffusion, provide a qualitatively good match to the main features of the data. This in turn allows us to deduce ice crystal properties. Since the wavelength of the detected light is short compared to the crystal size, these crystal properties include not only the crystal orientation fabric, but also the average crystal size and shape, as a function of depth. By adding small empirical corrections to this first-principles model, a quantitatively accurate description of the optical properties of the IceCube glacial ice is obtained. In this paper, we present the experimental signature of ice optical anisotropy observed in IceCube light-emitting diode (LED) calibration data, the theory and parameterization of the birefringence effect, the fitting procedures of these parameterizations to experimental data, and the inferred crystal properties.

Previous detections of individual astrophysical sources of neutrinos are limited to the Sun and the supernova 1987A, whereas the origins of the diffuse flux of high-energy cosmic neutrinos remain unidentified. On 22 September 2017, we detected a high-energy neutrino, IceCube-170922A, with an energy of ~290 tera-electron volts. Its arrival direction was consistent with the location of a known γ-ray blazar, TXS 0506+056, observed to be in a flaring state. An extensive multiwavelength campaign followed, ranging from radio frequencies to γ-rays. These observations characterize the variability and energetics of the blazar and include the detection of TXS 0506+056 in very-high-energy γ-rays. This observation of a neutrino in spatial coincidence with a γ-ray-emitting blazar during an active phase suggests that blazars may be a source of high-energy neutrinos.