Recombinant live vaccine candidates against tuberculosis

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Highlights? A robust pipeline of recombinant live TB vaccines aims to replace BCG. ? Current candidates are better than BCG in controlling TB in preclinical models. ? Three candidates in clinical trials signal hope for medium-term market introduction. ? Candidates do not prevent or eradicate infection. ? BCG can serve as vaccine platform to address the needs of diseases other than TB.     

Genetic engineering of attenuated malaria parasites for vaccination

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Highlights? Genetically attenuated parasites (GAPs) as potential vaccines against malaria. ? Attenuated Plasmodium sporozoites confer sustained sterile immunity against malaria. ? Rodent malaria models are an important in vivo platform to delineate GAP safety and potency. ? Late liver-arresting GAPs elicit superior protective immunity than early arresting parasites. ? P. falciparum GAP vaccine candidates need ultimately to be validated in clinical studies.     

Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling

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Highlights? Supernumerary centrosomes nucleate cilia, resulting in superciliated cells (SCC) ? Ciliary proteins are reduced in concentration in SCC, compromising signaling ? Presence of extra cilia disrupts epithelial organization in 3D spheroid culture ? Extra cilia may contribute to disease phenotypes by disrupting signaling     

Zinc Drives a Tertiary Fold in the Prion Protein with Familial Disease Mutation Sites at the Interface

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Highlights? Zinc binds to the prion protein octarepeat domain ? The zinc-bound octarepeat makes a tertiary contact to C-terminal helices 2 and 3 ? The encompassed surface carries a majority of the mutations in familial prion disease ? Familial mutations weaken this zinc-driven tertiary contact     

All-Atom Ensemble Modeling to Analyze Small-Angle X-Ray Scattering of Glycosylated Proteins

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Highlights? MW determined from zero angle scattering is accurate for glycoproteins ? All-atom modeling with SAXS data can identify structural features of glycans ? SAXS ab initio reconstructions provide little structural information for glycans     

A position-specific distance-dependent statistical potential for protein structure and functional study

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Highlights? Protein and position-specific statistical potentials are more powerful ? Evolutionary information greatly boost performance of statistical potentials ? Observed probability is critical to energy potentials, in addition to reference state ? Observed probability can be estimated better using context-specific information     

Direct and Indirect Gene Regulation by a Life-Extending FOXO Protein in C. elegans: Roles for GATA Factors and Lipid Gene Regulators

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Highlights? DAF-16 regulates genes both cell autonomously and cell nonautonomously ? DAF-16 can act at in the endoderm to delay muscle aging ? DAF-16 can act at a distance to protect animals from amyloid paralysis ? Cell-non-autonomous gene regulation by DAF-16 involves the lipid-gene regulator MDT-15     

The Crystal Structures of the Eukaryotic Chaperonin CCT Reveal Its Functional Partitioning

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Highlights? CCT subunit types can be identified in crystallographic data, even at low resolutions ? Actin and tubulin both bind around CCT6 ? ATP hydrolysis and substrate binding are partitioned in the CCT particle     

PGRL1 Is the Elusive Ferredoxin-Plastoquinone Reductase in Photosynthetic Cyclic Electron Flow

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Highlights? PGRL1 is the elusive FQR which has been sought for almost three decades ? PGR5 is required for the transfer of electrons from ferredoxin to PGRL1 ? The six redox-active cysteine residues of PGRL1 can form intra- and intermolecular disulfide bridges ? Thioredoxins destabilize PGRL1 homodimers     

Intrinsic negative feedback governs activation surge in two-component regulatory systems

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Highlights? Activation surge reconstituted in vitro with purified SK and RR ? ADP can be endogenously generated from ATP to stimulate an SK's phosphatase activity ? SK's affinity for ADP governs the switch from the kinase to phosphatase state ? Lid region of SK PhoQ controls its phosphatase activity and surge of RR PhoP     

Adipose Vascular Endothelial Growth Factor Regulates Metabolic Homeostasis through Angiogenesis

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Highlights? Two-way modulations of adipose VEGF were generated with aP2-Cre transgene ? Adipose VEGF KO reduces vasculature, increases hypoxia and inflammation in fat ? Adipose VEGF KO accelerates the development of metabolic disease in high-fat diet ? Induced adipose VEGF has opposite effect on fat and restores metabolic homeostasis     

DOLORS: Versatile Strategy for Internal Labeling and Domain Localization in Electron Microscopy

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Highlights? DOLORS is a strategy for EM labeling using AviTag and streptavidin ? Internal domains within a large protein can be labeled and identified ? Higher accuracy and precision are achieved by sampling multiple RCT reconstructions ? Offers a powerful method for deciphering moderate-resolution EM structures     

Decision Making during the Psychological Refractory Period

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Highlights? The PRP interferes with decision making and routing to the motor response ? Sensory evidence accumulation can occur for multiple decisions at the same time ? A large fraction of the PRP occurs after the commitment to a choice ? Evidence accumulation and sensory-motor mapping are distinct processes     

Structures of adnectin/protein complexes reveal an expanded binding footprint

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Highlights? Adnectins interact with targets using multiple binding modes ? Residues outside of the diversified loops can interact with ligand ? Some fixed scaffold residues contribute to the binding energy ? Adnectins can interact with epitopes that may be inaccessible to antibodies     

RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor

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Highlights? Crystal structures of the cytokine-binding regions of OPG and RANK bound to RANKL ? High-affinity OPG engagement is associated with a distinct RANKL-binding cleft ? Structural basis of how the OPG^F96L mutation promotes juvenile Paget’s disease     

Myosin-V Opposes Microtubule-Based Cargo Transport and Drives Directional Motility on Cortical Actin

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Highlights? Myosin-V alternates between active and passive actin-binding modes ? Myosin-V opposes kinesin-propelled cargo redistribution ? Myosin-V anchors kinesin-propelled cargo in actin-rich areas ? Myosin-V can drive medium-range directional transport at the cell periphery     

Disease mutations in the ryanodine receptor central region: crystal structures of a phosphorylation hot spot domain

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Highlights? Crystal structures of a central RyR domain contain phosphorylation sites ? Eleven RyR1 disease mutations cluster on two opposite faces of the domain ? The RyR1 L2867G mutation causes a drastic destabilization ? In vitro phosphorylation identifies 5 PKA and 4 CaMKII targets     

Biologically and chemically mediated adsorption and precipitation of phosphorus from wastewater

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Highlights? Phosphorus (P) ineffluent can be removed by biological/chemical-driven adsorption and precipitation. ? Phosphorus adsorption by filters and struvite formation are promising options in this field. ? Emerging adsorption approaches include P removal by polymers/nanomaterials.