SARS-CoV-2 Omicron virus causes attenuated disease in mice and hamsters.

The recent emergence of B.1.1.529, the Omicron variant1,2, has raised concerns of escape from protection by vaccines and therapeutic antibodies. A key test for potential countermeasures against B.1.1.529 is their activity in preclinical rodent models of respiratory tract disease. Here, using the collaborative network of the SARS-CoV-2 Assessment of Viral Evolution (SAVE) programme of the National Institute of Allergy and Infectious Diseases (NIAID), we evaluated the ability of several B.1.1.529 isolates to cause infection and disease in immunocompetent and human ACE2 (hACE2)-expressing mice and hamsters. Despite modelling data indicating that B.1.1.529 spike can bind more avidly to mouse ACE2 (refs. 3,4), we observed less infection by B.1.1.529 in 129, C57BL/6, BALB/c and K18-hACE2 transgenic mice than by previous SARS-CoV-2 variants, with limited weight loss and lower viral burden in the upper and lower respiratory tracts. In wild-type and hACE2 transgenic hamsters, lung infection, clinical disease and pathology with B.1.1.529 were also milder than with historical isolates or other SARS-CoV-2 variants of concern. Overall, experiments from the SAVE/NIAID network with several B.1.1.529 isolates demonstrate attenuated lung disease in rodents, which parallels preliminary human clinical data.

Co-Circulation of 2 Oropouche Virus Lineages, Amazon Basin, Colombia, 2024.

In early 2024, explosive outbreaks of Oropouche virus (OROV) linked to a novel lineage were documented in the Amazon Region of Brazil. We report the introduction of this lineage into Colombia and its co-circulation with another OROV lineage. Continued surveillance is needed to prevent further spread of OROV in the Americas.

Geometrical impacts of platonic particles on nematic liquid crystal dynamics.

Platonic-solid-like particles in liquid crystals offer intriguing opportunities for engineering complex materials with tailored properties. Inspired by platonic solids' geometric simplicity and symmetry, these particles possess well-defined shapes such as cubes, tetrahedra, octahedra, dodecahedra, and icosahedra. When dispersed within nematic liquid-crystalline media, these particles interact with the surrounding medium in intricate ways, influencing the local orientational order of liquid crystal molecules. In this work, we implement continuum simulations to study how the combination of particle shape and surface anchoring gives rise to line defects that follow the edges of the particles and how they are affected by the presence of a Poiseuille flow. Platonic-solid-like particles in liquid crystals have shown promise in diverse applications ranging from photonics and metamaterials to colloidal self-assembly and responsive soft materials.

Multiplex PCR assays developed for neglected pathogen detection in undifferentiated acute febrile illness cases in tropical regions.

BACKGROUND: Undifferentiated acute febrile illness (UAFI) cause by several pathogens poses a diagnostic challenge due to the similarity on the clinical manifestations across these diseases. Precise pathogen detection is vital for appropriate medical intervention, early treatment, and timely outbreak alerts regarding emerging pathogens. In tropical regions, UAFI is predominantly linked to a wide range of viral, bacterial, and parasitic infections. Hence, confirmatory laboratory tests are essential for specific pathogen identification. OBJECTIVES: Our primary goal was to develop two real-time multiplex polymerase chain reaction (PCR) assays for simultaneous detection of six neglected pathogens (Leptospira spp., Rickettsia spp., Borrelia spp., Anaplasma spp., Brucella spp., and Bartonella spp.), known for causing UAFI in tropical regions. METHODS: We rigorously assessed assays parameters including: linearity, efficiency, sensitivity, and reproducibility in both singleplex and multiplex formats. FINDINGS: Our results demonstrated that these multiplex assays are reliable and sensitive methods. They showed good performance with low intra- and inter-variability (< 10%) and consistently high efficiencies (> 90%). MAIN CONCLUSIONS: These assays offer the alternative of streamlining work, reducing processing costs, and minimizing sample volume use. In conclusion, we present two dependable, user-friendly, rapid, and cost-effective methods for simultaneously detecting six neglected bacteria, as a significant laboratory tool in resource-limited tropical settings.

Molecular Surveillance Detects High Prevalence of the Neglected Parasite Mansonella ozzardi in the Colombian Amazon.

BACKGROUND: Mansonellosis is an undermapped insect-transmitted disease caused by filarial nematodes that are estimated to infect hundreds of millions of people. Despite their prevalence, there are many outstanding questions regarding the general biology and health impacts of the responsible parasites. Historical reports suggest that the Colombian Amazon is endemic for mansonellosis and may serve as an ideal location to pursue these questions. METHODS: We deployed molecular and classical approaches to survey Mansonella prevalence among adults belonging to indigenous communities along the Amazon River and its tributaries near Leticia, Colombia. RESULTS: Loop-mediated isothermal amplification (LAMP) assays on whole-blood samples detected a much higher prevalence of Mansonella ozzardi infection (approximately 40%) compared to blood smear microscopy or LAMP performed using plasma, likely reflecting greater sensitivity and the ability to detect low microfilaremias and occult infections. Mansonella infection rates increased with age and were higher among men. Genomic analysis confirmed the presence of M. ozzardi that clusters closely with strains sequenced in neighboring countries. We successfully cryopreserved M. ozzardi microfilariae, advancing the prospects of rearing infective larvae in controlled settings. CONCLUSION: These data suggest an underestimation of true mansonellosis prevalence, and we expect that these methods will help facilitate the study of mansonellosis in endemic and laboratory settings.

Curvature and confinement effects on chiral liquid crystal morphologies.

Chiral liquid crystals (ChLCs) exhibit an inherent twist that originates at the molecular scale and can extend over multiple length scales when unconstrained. Under confinement, the twist is thwarted, leading to formation of defects in the molecular order that offer distinct optical responses and opportunities for colloidal driven assembly. Past studies have explored spheroidal confinement down to the nanoscopic regime, where curved boundaries produce surface defects to accommodate topological constraints and restrict the propagation of cuboidal defect networks. Similarly, strict confinement in channels and shells has been shown to give rise to escaped configurations and skyrmions. However, little is known about the role of extrinsic curvature in the development of cholesteric textures and Blue Phases (BP). In this paper, we examine the palette of morphologies that arises when ChLCs are confined in toroidal and cylindrical cavities. The equilibrium morphologies are obtained following an annealing strategy of a Landau-de Gennes free energy functional. Three dimensionless groups are identified to build phase diagrams: the natural twist, the ratio of elastic energies, and the circumscription of a BP cell. Curvature is shown to introduce helical features that are first observed as a Double Twist, and progress to Chiral Ribbons and, ultimately, Helical BP and BP. Chiral ribbons are examined as useful candidates for driven assembly given their tunability and robustness.

Geometrically driven aggregation of unsymmetrical dielectric particles.

Understanding electrostatic interactions among dielectric bodies in the atmosphere and aerosols is central to controlling their aggregation. Polarization effects, which are frequently ignored, are crucial to determine interactions when geometrical anisotropies are present due to surface-induced charge segregation. Here, we adopt a direct integral formulation that accounts for the problem of charged dielectric bodies immersed in a continuum media to explore particle aggregation via geometrical tuning. We show that by breaking the structural symmetry and modifying the close-contact surface between particles of equal charge, it is possible to obtain attractive regimes at short and long distances. We evaluate the electrostatic forces and energy of a set of dimers and trimers composed of spheres, oblates, and prolates in a vacuum, where no counter-ions are present, to construct a phase diagram with the conditions required to form stable aggregates as a function of the geometrical anisotropy. We found that it is possible to direct the aggregation (or dispersion) of two and three positive dielectric particles by adjusting their geometry and controlling the contact surface among them. Our results give insight into a way to control the aggregation of dielectric systems and offer a prospect for directing the assembly of complex particle structures.

Directing the far-from-equilibrium assembly of nanoparticles in confined liquid crystals by hydrodynamic fields.

The assembly of nematic colloids relies on long-range elastic interactions that can be manipulated through external stimuli. Confinement and the presence of a hydrodynamic field alter the defect structures and the energetic interactions between the particles. In this work, the assembly landscape of nanoparticles embedded in a nematic liquid crystal confined in a nanochannel under a pressure-driven flow is determined. The dynamics of the liquid crystal tensor alignment field is determined through a Poisson-Bracket framework, namely the Stark-Lubensky equations, coupled with the zero-Reynolds momentum equations and the liquid crystal Landau-de Gennes free energy functional. A second order semi-implicit time integration and a three-dimensional Galerkin finite element method are used to resolve flow and nematic fields under several conditions. In general, the zero Reynolds flow displaces the defects around the particles in the upstream direction and renders the surface anchoring ineffective when the flow strength dominates over the nematic elasticity. More importantly, the potential of mean force for particle assembly is non-monotonic independent of surface anchoring. Our results show that the confinement length scale determines the repulsion/attraction transition between colloids, while the flow strength modifies the static defect structure surrounding the particles and determines the magnitude of the energetic barrier for successful assembly. In the attractive regime, the particles move at different rates through the nematic until one particle eventually catches up with the other. This process occurs against or along the direction of flow depending on the flow strength. Ultimately, these results provide a template for engineering and controlling the transport and assembly of nanoparticles under far-from equilibrium conditions in anisotropic media.

Cuboidal liquid crystal phases under multiaxial geometrical frustration.

Cuboidal liquid crystal phases - the so-called blue phases - consist of a network of topological defects arranged into a cubic symmetry. They exhibit striking optical properties, including Bragg reflection in the visible range and fast response times. Confining surfaces can interfere with the packing of such a network, leading to structures that have not been explored before. In this work, a Landau-de Gennes free energy formalism for the tensor alignment field Q is used to investigate the behavior of chiral liquid crystals under non-isotropic confinement. The underlying free energy functional is solved by relying on a Monte Carlo method that facilitates efficient exploration of configuration space. The results of simulations are expressed in terms of phase diagrams as a function of chirality and temperature for three families of spheroids: oblate, spherical, and prolate. Upon deformation, blue phases adapt and transform to accommodate the geometrical constraints, thereby resulting in a wider range of thermal stability. For oblate spheroids, confinement interferes with the development of a full blue phase structure, resulting on a combination of half skyrmions. For prolate spheroids, the blue phases are hybridized and exhibit features of blue phases I and II. More generally, it is shown that mechanical deformation provides an effective means to control, manipulate and stabilize blue phases and cholesterics confined in tactoids.

Structure and dynamics of hydrodynamically interacting finite-size Brownian particles in a spherical cavity: Spheres and cylinders.

The structure and dynamics of confined suspensions of particles of arbitrary shape are of interest in multiple disciplines from biology to engineering. Theoretical studies are often limited by the complexity of long-range particle-particle and particle-wall forces, including many-body fluctuating hydrodynamic interactions. Here, we report a computational study on the diffusion of spherical and cylindrical particles confined in a spherical cavity. We rely on an immersed-boundary general geometry Ewald-like method to capture lubrication and long-range hydrodynamics and include appropriate non-slip conditions at the confining walls. A Chebyshev polynomial approximation is used to satisfy the fluctuation-dissipation theorem for the Brownian suspension. We explore how lubrication, long-range hydrodynamics, particle volume fraction, and shape affect the equilibrium structure and the diffusion of the particles. It is found that once the particle volume fraction is greater than 10%, the particles start to form layered aggregates that greatly influence particle dynamics. Hydrodynamic interactions strongly influence the particle diffusion by inducing spatially dependent short-time diffusion coefficients, stronger wall effects on the particle diffusion toward the walls, and a sub-diffusive regime-caused by crowding-in the long-time particle mobility. The level of asymmetry of the cylindrical particles considered here is enough to induce an orientational order in the layered structure, decreasing the diffusion rate and facilitating a transition to the crowded mobility regime at low particle concentrations. Our results offer fundamental insights into the diffusion and distribution of globular and fibrillar proteins inside cells.

Mesoscale martensitic transformation in single crystals of topological defects.

Liquid-crystal blue phases (BPs) are highly ordered at two levels. Molecules exhibit orientational order at nanometer length scales, while chirality leads to ordered arrays of double-twisted cylinders over micrometer scales. Past studies of polycrystalline BPs were challenged by the existence of grain boundaries between randomly oriented crystalline nanodomains. Here, the nucleation of BPs is controlled with precision by relying on chemically nanopatterned surfaces, leading to macroscopic single-crystal BP specimens where the dynamics of mesocrystal formation can be directly observed. Theory and experiments show that transitions between two BPs having a different network structure proceed through local reorganization of the crystalline array, without diffusion of the double-twisted cylinders. In solid crystals, martensitic transformations between crystal structures involve the concerted motion of a few atoms, without diffusion. The transformation between BPs, where crystal features arise in the submicron regime, is found to be martensitic in nature when one considers the collective behavior of the double-twist cylinders. Single-crystal BPs are shown to offer fertile grounds for the study of directed crystal nucleation and the controlled growth of soft matter.

Electrostatic confinement and manipulation of DNA molecules for genome analysis.

Very large DNA molecules enable comprehensive analysis of complex genomes, such as human, cancer, and plants because they span across sequence repeats and complex somatic events. When physically manipulated, or analyzed as single molecules, long polyelectrolytes are problematic because of mechanical considerations that include shear-mediated breakage, dealing with the massive size of these coils, or the length of stretched DNAs using common experimental techniques and fluidic devices. Accordingly, we harness analyte "issues" as exploitable advantages by our invention and characterization of the "molecular gate," which controls and synchronizes formation of stretched DNA molecules as DNA dumbbells within nanoslit geometries. Molecular gate geometries comprise micro- and nanoscale features designed to synergize very low ionic strength conditions in ways we show effectively create an "electrostatic bottle." This effect greatly enhances molecular confinement within large slit geometries and supports facile, synchronized electrokinetic loading of nanoslits, even without dumbbell formation. Device geometries were considered at the molecular and continuum scales through computer simulations, which also guided our efforts to optimize design and functionalities. In addition, we show that the molecular gate may govern DNA separations because DNA molecules can be electrokinetically triggered, by varying applied voltage, to enter slits in a size-dependent manner. Lastly, mapping the Mesoplasmaflorum genome, via synchronized dumbbell formation, validates our nascent approach as a viable starting point for advanced development that will build an integrated system capable of large-scale genome analysis.

Structure and proton conduction in sulfonated poly(ether ether ketone) semi-permeable membranes: a multi-scale computational approach.

The design of polymeric membranes for proton or ionic exchange highly depends on the fundamental understanding of the physical and molecular mechanisms that control the formation of the conduction channels. There is an inherent relation between the dynamical structure of the polymeric membrane and the electrostatic forces that drive membrane segregation and proton transport. Here, we used a multi-scale computational approach to analyze the morphology of sulfonated poly(ether ether ketone) membranes at the mesoscale. A self-consistent description of the electrostatic phenomenon was adopted, where discrete polymer chains and a continuum proton field were embedded in a continuum fluid. Brownian dynamics was used for the evolution of the suspended polymer molecules, while a convection-diffusion transport equation, including the Nernst-Planck diffusion mechanism, accounted for the dynamics of the proton concentration field. We varied the polymer concentration, the degree of sulfonation and the level of confinement to find relationships between membrane structure and proton conduction. Our results indicate that the reduced mobility of polymer chains, at concentrations above overlap, and a moderate degree of sulfonation - i.e., 30% - are essential elements for membrane segregation and proton domain connectivity. These conditions also ensure that the membrane structure is not affected by size or by potential gradients. Importantly, our analysis shows that membrane conductivity and current are linearly dependent on polymer concentration and quadratically dependent on the degree of sulfonation. We found that the optimal polymeric membrane design requires a polymer concentration above overlap and a degree of sulfonation around 50%. These conditions promote a dynamical membrane morphology with a constant density of proton channels. Our results and measurements agree with previous experimental works, thereby validating our model and observations.

Active fluid with Acidithiobacillus ferrooxidans: correlations between swimming and the oxidation route.

To explore engineering platforms towards 'active bacterial baths', we grow and characterize native and commercial strains of Acidithiobacillus ferrooxidans to promote swimming locomotion. Three different energy sources were used, namely elemental sulfur, ferrous sulfate, and pyrite. The characteristics of the culture, such as pH, Eh, and the concentration of cells and ions, are monitored to seek correlations between the oxidation route and the transport mechanism. We found that only elemental sulfur induces swimming mobility in the commercial DSMZ - 24,419 strain, while ferrous sulfate and the sulfide mineral, pyrite, did not activate swimming on any strain. The bacterial mean squared displacement and the mean velocity are measured to provide a quantitative description of the bacterial mobility. We found that, even if the A. ferrooxidans strain is grown in a sulfur-rich environment, it preferentially oxidizes iron when an iron-based material is included in the media. Similar to other species, once the culture pH decreases below 1.2, the active locomotion is inhibited. The engineering control and activation of swimming in bacterial cultures offer fertile grounds towards applications of active suspensions such as energy-efficient bioleaching, mixing, drug delivery, and bio-sensing.

Parallel O(N) Stokes' solver towards scalable Brownian dynamics of hydrodynamically interacting objects in general geometries.

An efficient parallel Stokes' solver has been developed for complete description of hydrodynamic interactions between Brownian particles in bulk and confined geometries. A Langevin description of the particle dynamics is adopted, where the long-range interactions are included using a Green's function formalism. A scalable parallel computational approach is presented, where the general geometry Stokeslet is calculated following a matrix-free algorithm using the general geometry Ewald-like method. Our approach employs a highly efficient iterative finite-element Stokes' solver for the accurate treatment of long-range hydrodynamic interactions in arbitrary confined geometries. A combination of mid-point time integration of the Brownian stochastic differential equation, the parallel Stokes' solver, and a Chebyshev polynomial approximation for the fluctuation-dissipation theorem leads to an O(N) parallel algorithm. We illustrate the new algorithm in the context of the dynamics of confined polymer solutions under equilibrium and non-equilibrium conditions. The method is then extended to treat suspended finite size particles of arbitrary shape in any geometry using an immersed boundary approach.

Solubilization of phosphorus from phosphate rocks with Acidithiobacillus thiooxidans following a growing-then-recovery process.

Phosphorus is an essential nutrient for the synthesis of biomolecules and is particularly important in agriculture, as soils must be constantly supplemented with its inorganic form to ensure high yields and productivity. In this paper, we propose a process to solubilize phosphorus from phosphate rocks, where Acidithiobacillus thiooxidans cultures are pre-cultivated to foster the acidic conditions for bioleaching-two-step "growing-then-recovery"-. Our method solubilizes 100% of phosphorus, whereas the traditional process without pre-cultivation-single-step "growing-and-recovery"-results in a maximum of 56% solubilization. As a proof of principle, we demonstrate that even at low concentrations of the phosphate rock, 1% w/v, the bacterial culture is unviable and biological activity is not observed during the single-step process. On the other hand, in our method, the bacteria are grown without the rock, ensuring high acid production. Once pH levels are below 0.7, the mineral is added to the culture, resulting in high yields of biological solubilization. According to the Fourier Transform Infrared Spectroscopy spectrums, gypsum is the dominant phosphate phase after both the single- and two-step methods. However, calcite and fluorapatite, dominant in the un-treated rock, are still present after the single-step, highlighting the differences between the chemical and the biological methods. Our process opens new avenues for biotechnologies to recover phosphorus in tropical soils and in low-grade phosphate rock reservoirs.

Directed self-assembly of nematic liquid crystals on chemically patterned surfaces: morphological states and transitions.

The morphology and through-film optical properties of nematic liquid crystals (LCs) confined between two surfaces may be engineered to create switches that respond to external electric fields, thereby enabling applications in optoelectronics that require fast responses and low power. Interfacial properties between the confining surfaces and the LC play a central role in device design and performance. Here we investigate the morphology of LCs confined in hybrid cells with a top surface that exhibits uniform homeotropic anchoring and a bottom surface that is chemically patterned with sub-micron and micron- wide planar anchoring stripes in a background of homeotropic anchoring. In a departure from past work, we first investigate isolated stripes, as opposed to dense periodic arrays of stripes, thereby allowing for an in-depth interpretation of the effects of patterning on LC morphology. We observe three LC morphologies and sharp transitions between them as a function of stripe width in the submicron and micron regimes. Numerical simulations and theory help explain the roles of anchoring energy, elastic deformation, entropy, pattern geometry, and coherence length of the LC in the experimentally observed behavior. The knowledge and models developed from an analysis of results generated on isolated features are then used to design dense patterned substrates for high-contrast and efficient orientational switching of LCs in response to applied fields.

A clone-free, single molecule map of the domestic cow (Bos taurus) genome.

BACKGROUND: The cattle (Bos taurus) genome was originally selected for sequencing due to its economic importance and unique biology as a model organism for understanding other ruminants, or mammals. Currently, there are two cattle genome sequence assemblies (UMD3.1 and Btau4.6) from groups using dissimilar assembly algorithms, which were complemented by genetic and physical map resources. However, past comparisons between these assemblies revealed substantial differences. Consequently, such discordances have engendered ambiguities when using reference sequence data, impacting genomic studies in cattle and motivating construction of a new optical map resource--BtOM1.0--to guide comparisons and improvements to the current sequence builds. Accordingly, our comprehensive comparisons of BtOM1.0 against the UMD3.1 and Btau4.6 sequence builds tabulate large-to-immediate scale discordances requiring mediation. RESULTS: The optical map, BtOM1.0, spanning the B. taurus genome (Hereford breed, L1 Dominette 01449) was assembled from an optical map dataset consisting of 2,973,315 (439 X; raw dataset size before assembly) single molecule optical maps (Rmaps; 1 Rmap = 1 restriction mapped DNA molecule) generated by the Optical Mapping System. The BamHI map spans 2,575.30 Mb and comprises 78 optical contigs assembled by a combination of iterative (using the reference sequence: UMD3.1) and de novo assembly techniques. BtOM1.0 is a high-resolution physical map featuring an average restriction fragment size of 8.91 Kb. Comparisons of BtOM1.0 vs. UMD3.1, or Btau4.6, revealed that Btau4.6 presented far more discordances (7,463) vs. UMD3.1 (4,754). Overall, we found that Btau4.6 presented almost double the number of discordances than UMD3.1 across most of the 6 categories of sequence vs. map discrepancies, which are: COMPLEX (misassembly), DELs (extraneous sequences), INSs (missing sequences), ITs (Inverted/Translocated sequences), ECs (extra restriction cuts) and MCs (missing restriction cuts). CONCLUSION: Alignments of UMD3.1 and Btau4.6 to BtOM1.0 reveal discordances commensurate with previous reports, and affirm the NCBI's current designation of UMD3.1 sequence assembly as the "reference assembly" and the Btau4.6 as the "alternate assembly." The cattle genome optical map, BtOM1.0, when used as a comprehensive and largely independent guide, will greatly assist improvements to existing sequence builds, and later serve as an accurate physical scaffold for studies concerning the comparative genomics of cattle breeds.

Homeotropic nano-particle assembly on degenerate planar nematic interfaces: films and droplets.

A continuum theory is used to study the effects of homeotropic nano-particles on degenerate planar liquid crystal interfaces. Particle self-assembly mechanisms are obtained from careful examination of particle configurations on a planar film and on a spherical droplet. The free energy functional that describes the system is minimized according to Ginzburg-Landau and stochastic relaxations. The interplay between elastic and surface distortions and the desire to minimize defect volumes (boojums and half-Saturn rings) is shown to be responsible for the formation of intriguing ordered structures. As a general trend, the particles prefer to localize at defects to minimize the overall free energy. However, multiple metastable configurations corresponding to local minima can be easily observed due to the high energy barriers that separate distinct particle arrangements. We also show that by controlling anchoring strength and temperature one can direct liquid-crystal mediated nanoparticle self-assembly along well defined pathways.