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.     

Pharmaceutical protein production by yeast: towards production of human blood proteins by microbial fermentation

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Highlights? Recombinant therapeutic protein production is a multibillion dollar market. ? E. coli comprises 30% of recombinant protein production but not suitable for human therapeutics. ? Eukaryotic systems other than yeast are costly or not so efficient regarding protein yields. ? S. cerevisiae shows a high potential to be a suitable platform for therapeutic proteins. ? Human blood proteins are the next candidates to be challenged by S. cerevisiae system.     

Killed but metabolically active vaccines

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Highlights? KBMA vaccines are whole photochemically inactivated organisms and cannot cause disease yet retain metabolic activity. ? KBMA vaccines lack nucleotide excision repair and are exquisitely sensitive to inactivation by psoralen and UVA light. ? KBMA vaccines can encode recombinant antigens relevant to infectious disease or cancer. ? KBMA vaccines derived from an attenuated selected pathogen present the entire antigenic repertoire to the immune system. ? The KBMA technology can also be used to generate vaccine candidates from protozoan pathogens such as Leishmania species.     

Keeping cell identity in Arabidopsis requires PRC1 RING-finger homologs that catalyze H2A monoubiquitination

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Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination     

Recognizing protein-ligand binding sites by global structural alignment and local geometry refinement

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Highlights? A protein-ligand binding method combining structure and evolutionary insights ? Large-scale test and validation on both benchmark and blind experiments ? Comprehensive and deep analysis on what works and what does not ? Ligand binding prediction with accuracy higher than the state-of-the-art methods     

Perivascular Nitric Oxide Activates Notch Signaling and Promotes Stem-like Character in PDGF-Induced Glioma Cells

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Highlights? Perivascular niche nitric oxide activates Notch in PDGF-induced gliomas ? Notch signaling drives tumor stem-like characteristics and reduces survival ? Loss of eNOS activity decreases tumor stem-like characteristics ? Suppressing eNOS activity prolongs survival in glioma-bearing mice     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

Genetic Control of Obesity and Gut Microbiota Composition in Response to High-Fat,High-Sucrose Diet in Mice

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Highlights? Detailed analysis of diet-induced obesity in more than 100 inbred mouse strains ? Identification of 11 genetic loci associated with obesity and dietary responsiveness ? Significant overlap between mouse loci with human GWAS loci for obesity ? Strain-specific shifts in gut microbiota composition in response to dietary intervention     

Comprehensive Analysis of Silencing Mutants Reveals Complex Regulation of the Arabidopsis Methylome

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Highlights? Genome-wide single-nucleotide resolution methylation maps in 86 silencing mutants ? Complex interplays between different DNA methylation pathways ? Identification of novel regulators of DNA methylation     

A comprehensive genomic binding map of gene and chromatin regulatory proteins in Saccharomyces

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Highlights? Genomic maps of 200 yeast regulators in normal and stress conditions provide a compendium for discovery ? SAGA assembly pathway is associated with more regulation than the TFIID pathway ? SAGA-linked regulators are distal, and TFIID-linked regulators are proximal to the promoter ? During heat shock, SAGA- and TFIID-linked regulators displayed distinct mobilization patterns     

The Centrosome Regulates the Rab11- Dependent Recycling Endosome Pathway at Appendages of the Mother Centriole

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Highlights? Endosome-proteins localize to centrosomes independent of membranes ? Rab11 and its modulators localize to mother centriole appendages ? Mother centriole appendages regulate membrane recycling through Rab11     

Tremor Suppression by Rhythmic Transcranial Current Stimulation

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Highlights? Phase-cancelling cortical stimulation attenuates Parkinsonian tremor ? Prolonged stimulation may invoke adaptive mechanisms ? Phase cancellation may provide a generic treatment approach to oscillopathies ? TACS provides a convenient probe of cortical circuit dynamics in humans     

Vervet Monkeys Solve a Multiplayer “Forbidden Circle Game” by Queuing to Learn Restraint

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Highlights? Vervet monkeys (one captive, two wild groups) solved a multiplayer coordination problem ? All those dominant to food provider had to leave “forbidden circle” around dispenser ? The animals discovered all fundamentals of the game structure without human guidance ? Individual learning and patience, rather than communication or coercion, were decisive     

Protein model discrimination using mutational sensitivity derived from deep sequencing

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Highlights? Individual mutant phenotypes in a saturation library derived via deep sequencing ? Residue depth and active-site residue derivation from mutant phenotypes ? Mutant-phenotype-derived parameters used for protein model discrimination ? Derivation of sequence-structure-function relationships without protein isolation     

Hypertrophy and unconventional cell division of hepatocytes underlie liver regeneration

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Highlights? Not all hepatocytes undergo cell division during liver regeneration ? Hypertrophy precedes proliferation in the regenerating liver ? Hepatocytes infrequently enter into M phase during liver regeneration ? Binuclear hepatocytes undergo cell division to generate mononuclear hepatocytes     

MTR1 encodes a secretory fasciclin glycoprotein required for male reproductive development in rice

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Highlights? The fasciclin glycoprotein MTR1 regulates male reproductive development in rice ? Rice male reproductive cells secrete MTR1 to control somatic tapetum development     

ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

A Dodecameric CcmK2 Structure Suggests β-Carboxysomal Shell Facets Have a Double-Layered Organization

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Highlights? CcmK2 shows a far stronger self-interaction than do other CcmK paralogs ? CcmK2 forms dodecamers via interactions of the αD helix on the concave face ? Hexagonally tiled CcmK2 sheets can weld via this interaction into a double layer ? FRET data supports a double-layered concave-to-concave model of the shell