Nearly all clinical isolates of Salmonella Typhi, the cause of typhoid fever, are antibiotic resistant. All S. Typhi isolates secrete an A2B5 exotoxin called typhoid toxin to benefit the pathogen during infection. Here, we demonstrate that antibiotic-resistant S. Typhi secretes typhoid toxin continuously during infection regardless of antibiotic treatment. We characterize typhoid toxin antibodies targeting glycan-receptor-binding PltB or nuclease CdtB, which neutralize typhoid toxin in vitro and in vivo, as demonstrated by using typhoid toxin secreted by antibiotic-resistant S. Typhi during human cell infection and lethal dose typhoid toxin challenge to mice. TyTx11 generated in this study neutralizes typhoid toxin effectively, comparable to TyTx4 that binds to all PltB subunits available per holotoxin. Cryoelectron microscopy explains that the binding of TyTx11 to CdtB makes this subunit inactive through CdtB catalytic-site conformational change. The identified toxin-neutralizing epitopes are conserved across all S. Typhi clinical isolates, offering critical insights into typhoid toxin-neutralizing strategies.In terms of genome and particle sizes, viruses exhibit great diversity. With the discovery of several nucleocytoplasmic large DNA viruses (NCLDVs) and jumbo phages, the relationship between particle and genome sizes has emerged as an important criterion for understanding virus evolution. We use allometric scaling of capsid volume with the genome length of different groups of viruses to shed light on its relationship with virus life history. The allometric exponents for icosahedral dsDNA bacteriophages and NCDLVs were found to be 1 and 2, respectively, indicating that with increasing capsid size DNA packaging density remains the same in bacteriophages but decreases for NCLDVs. We argue that the exponents are largely shaped by their entry mechanism and capsid mechanical stability. We further show that these allometric size parameters are also intricately linked to the relative energy costs of translation and replication in viruses and can have further implications on viral life history.Top-down, context-dependent modulation of visual processing has been a topic of wide interest, including in mouse primary visual cortex (V1). However, the organization of feedback projections to V1 is relatively unknown. Here, we investigated inputs to mouse V1 by injecting retrograde tracers. We developed a software pipeline that maps labeled cell bodies to corresponding brain areas in the Allen Reference Atlas. We identified more than 24 brain areas that provide inputs to V1 and quantified the relative strength of their projections. We also assessed the organization of the projections, based on either the organization of cell bodies in the source area (topography) or the distribution of projections across V1 (bias). Projections from most higher visual and some nonvisual areas to V1 showed both topography and bias. Such organization of feedback projections to V1 suggests that parts of the visual field are differentially modulated by context, which can be ethologically relevant for a navigating animal.The copper efflux regulator (CueR), a representative member of mercury resistance regulator (MerR) family metalloregulators, controls expression of copper homeostasis-regulating genes in bacteria. The mechanism of transcription activation by CueR and other MerR family regulators is bending the spacer domain of promoter DNA. Here, we report the cryo-EM structures of the intact CueR-dependent transcription activation complexes. The structures show that CueR dimer bends the 19-bp promoter spacer to realign the -35 and -10 elements for recognition by σ70-RNA polymerase holoenzyme and reveal a previously unreported interaction between the DNA-binding domain (DBD) from one CueR subunit and the σ70 nonconserved region (σNCR). Functional studies have shown that the CueR-σNCR interaction plays an auxiliary role in CueR-dependent transcription, assisting the activation mechanism of bending promoter DNA by CueR dimer. Because DBDs are highly conserved in sequence and structure, this transcription-activating mechanism could be generally used by MerR family regulators.Unlike the conceptual models, the natural hydrate spatial distribution in sediments is multitype and presents different coalescence degrees. In this study, we present pore-scale triaxial test results for hydrate-bearing sediments with different hydrate spatial distributions for the first time. It shows that the specimen with a more dispersed hydrate distribution yields later and exhibits larger peak strength. Correspondingly, the localized deformation develops more slowly, and the shear band is steeper and thinner. find more The cementation failure in the specimen with a more dispersed hydrate distribution develops more slowly. However, the changing rate of the pore space characteristic does not seem to be affected by the hydrate spatial distribution. Moreover, the specimen with a more dispersed hydrate distribution has a larger hydrate-sand interfacial area, and further axial loading would increase it rapidly firstly, and then the increasing rate would be slowed down since the cementation structure failure.Tumor suppressor PTEN, the second most highly mutated protein in cancer, dephosphorylates signaling lipid PIP3 produced by PI3Ks. Excess PIP3 promotes cell proliferation. The mechanism at the membrane of this pivotal phosphatase is unknown hindering drug discovery. Exploiting explicit solvent simulations, we tracked full-length PTEN trafficking from the cytosol to the membrane. We observed its interaction with membranes composed of zwitterionic phosphatidylcholine, anionic phosphatidylserine, and phosphoinositides, including signaling lipids PIP2 and PIP3. We tracked its moving away from the zwitterionic and getting absorbed onto anionic membrane that harbors PIP3. We followed it localizing on microdomains enriched in signaling lipids, as PI3K does, and observed PIP3 allosterically unfolding the N-terminal PIP2 binding domain, positioning it favorably for the polybasic motif interaction with PIP2. Finally, we determined PTEN catalytic action at the membrane, all in line with experimental observations, deciphering the mechanisms of how PTEN anchors to the membrane and restrains cancer.