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THE FIELD OF PSYCHOLOGY NEVER MAXED OUT ON THE IDEAS OF MAX WERTHEIMER: A NEW LOOK AT PRODUCTIVE THINKING Productive Thinking By Max Wertheimer. Basel, Switzerland: Birkhauser/Springer, 2020 (original work [...]

INTRODUCTION Alcohol is the most commonly consumed substance among Americans ages 12 and older, and women are the fastest growing segment of alcohol consumers in the United States. (1,2) Female [...]

Bacteria use adaptive immune systems encoded by CRISPR and Cas genes to maintain genomic integrity when challenged by pathogens and mobile genetic elements.sup.1-3. Type I CRISPR-Cas systems typically target foreign DNA for degradation via joint action of the ribonucleoprotein complex Cascade and the helicase-nuclease Cas3.sup.4,5, but nuclease-deficient type I systems lacking Cas3 have been repurposed for RNA-guided transposition by bacterial Tn7-like transposons.sup.6,7. How CRISPR- and transposon-associated machineries collaborate during DNA targeting and insertion remains unknown. Here we describe structures of a TniQ-Cascade complex encoded by the Vibrio cholerae Tn6677 transposon using cryo-electron microscopy, revealing the mechanistic basis of this functional coupling. The cryo-electron microscopy maps enabled de novo modelling and refinement of the transposition protein TniQ, which binds to the Cascade complex as a dimer in a head-to-tail configuration, at the interface formed by Cas6 and Cas7 near the 3' end of the CRISPR RNA (crRNA). The natural Cas8-Cas5 fusion protein binds the 5' crRNA handle and contacts the TniQ dimer via a flexible insertion domain. A target DNA-bound structure reveals critical interactions necessary for protospacer-adjacent motif recognition and R-loop formation. This work lays the foundation for a structural understanding of how DNA targeting by TniQ-Cascade leads to downstream recruitment of additional transposase proteins, and will guide protein engineering efforts to leverage this system for programmable DNA insertions in genome-engineering applications. Cryo-electron microscopy structures of the TniQ-Cascade complex encoded by the Vibrio cholerae Tn6677 transposon reveal the mechanistic basis of the functional association of CRISPR- and transposon-associated machineries., Author(s): Tyler S. Halpin-Healy [sup.1] , Sanne E. Klompe [sup.1] , Samuel H. Sternberg [sup.1] , Israel S. Fernández [sup.1] Author Affiliations: (1) Department of Biochemistry and Molecular Biophysics, Columbia [...]

INTRODUCTION America has long prided itself on being a nation of mobility. A nation where if you just work hard enough, you can and will get ahead. (1) Indeed, many [...]

The Neuroscience of Intelligence By Richard J. Haier. New York, NY: Cambridge University Press, 2017. 270 pp. Paper, $37.99. In this review, I summarize main aspects of Richard J. Haier's [...]

Collaboration in Psychological Science: Behind the Sciences Edited by Richard L. Zweigenhaft and Eugene Borgida. New York, NY: Worth, 2016. 304 pp. Paper, $34.99. Many years ago, when I was [...]

Author(s): Janice S. Chen [1]; Yavuz S. Dagdas [2]; Benjamin P. Kleinstiver [3, 4, 5]; Moira M. Welch [3, 4]; Alexander A. Sousa [3, 4]; Lucas B. Harrington [1]; Samuel [...]

Author(s): R. Genzel (corresponding author) [1, 2]; N. M. Frster Schreiber (corresponding author) [1]; H. bler [1]; P. Lang [1]; T. Naab [3]; R. Bender [1, 4]; L. J. Tacconi [...]

Cas9 is an RNA-guided DNA endonuclease that targets foreign DNA for destruction as part of a bacterial adaptive immune system mediated by clustered regularly interspaced short palindromic repeats (CRISPR) (1,2). [...]

Conventional CRISPR-Cas systems maintain genomic integrity by leveraging guide RNAs for the nuclease-dependent degradation of mobile genetic elements, including plasmids and viruses. Here we describe a notable inversion of this paradigm, in which bacterial Tn7-like transposons have co-opted nuclease-deficient CRISPR-Cas systems to catalyse RNA-guided integration of mobile genetic elements into the genome. Programmable transposition of Vibrio cholerae Tn6677 in Escherichia coli requires CRISPR- and transposon-associated molecular machineries, including a co-complex between the DNA-targeting complex Cascade and the transposition protein TniQ. Integration of donor DNA occurs in one of two possible orientations at a fixed distance downstream of target DNA sequences, and can accommodate variable length genetic payloads. Deep-sequencing experiments reveal highly specific, genome-wide DNA insertion across dozens of unique target sites. This discovery of a fully programmable, RNA-guided integrase lays the foundation for genomic manipulations that obviate the requirements for double-strand breaks and homology-directed repair. A programmable transposase integrates donor DNA at user-defined genomic target sites with high fidelity, revealing a new approach for genetic engineering that obviates the need for DNA double-strand breaks and homologous recombination., Author(s): Sanne E. Klompe [sup.1] , Phuc L. H. Vo [sup.2] , Tyler S. Halpin-Healy [sup.1] , Samuel H. Sternberg [sup.1] Author Affiliations: (1) Department of Biochemistry and Molecular Biophysics, [...]

The Post-9/11 Veterans Educational Assistance Act of 2008 or 'New GI Bill' has resulted in rising enrollment and related demand for services by students in the USA. We examined current supports for student service members and veterans at institutions of higher education in Indiana in the context of this national trend. We employed prospective student service members who contacted campuses to ask staff and administrators about admissions, financial aid, academic, and student services policies and programs. Results showed that most institutions had the ability to refer to disability services, award credit for military training, and waive reapplication requirements following deployment. Few institutions reported support to military families or availability of student veterans' organizations. Institution type and size, degrees offered, and the presence of graduate programs were related to availability of programs and services. Considerable variability across campuses suggested opportunities to refine, coordinate, and expand assistance to student service members and veterans., Author(s): Stacie Hitt[sup.1] , Martina Sternberg[sup.1] , Shelley MacDermid Wadsworth[sup.1] , Joyce Vaughan[sup.1] , Rhiannon Carlson[sup.1] , Elizabeth Dansie[sup.1] , Martina Mohrbacher[sup.1] Author Affiliations: (1) Military Family Research Institute at [...]

Abstract How truck drivers spend their time is crucial to the profitability of motor carriers. However, the aspect of time has been marginally addressed in industry practice and academic literature [...]

The Malleability of Intellectual Styles By Li-Fang Zhang. Cambridge, England: Cambridge University Press, 2013. 378pp. Hardcover, $99.00. In her book on The Malleability of Intellectual Styles, Zhang presents abundant evidence [...]

Are We Getting Smarter? By James Flynn. Cambridge, England: Cambridge University Press, 2012. 324 pp. Paper, $24.99. It could safely be said that Are We Getting Smarter? is a generally [...]

The CRISPR-associated protein Cas9 is an RNA-guided DNA endonuclease that uses RNA-DNA complementarity to identify target sites for sequence-specific double-stranded DNA (dsDNA) cleavage (1-5).In its native context, Cas9 acts on DNA substrates exclusively because both binding and catalysis require recognition of a short DNA sequence, known as the protospacer adjacent motif (PAM), next to and on the strand opposite the twenty-nucleotide target site in dsDNA (4-7). Cas9 has proven to be a versatile tool for genome engineering and gene regulation in a large range of prokaryotic and eukaryotic cell types, and in whole organisms (8), but it has been thought to be incapable of targeting RNA5. Here we show that Cas9 binds with high affinity to single-stranded RNA (ssRNA) targets matching the Cas9-associated guide RNA sequence when the PAM is presented in transas a separate DNA oligonucleotide. Furthermore, PAM-presenting oligonucleotides (PAMmers) stimulate site-specific endonucleolytic cleavage of ssRNA targets, similar to PAM-mediated stimulation of Cas9-catalysed DNA cleavage (7). Using specially designed PAMmers, Cas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, and we demonstrate that this strategy enables the isolation of a specific endogenous messenger RNA from cells. These results reveal a fundamental connection between PAM binding and substrate selection by Cas9, and highlight the utility of Cas9 for programmable transcript recognition without the need for tags., CRISPR-Cas immune systems must discriminate between self and non-self to avoid an autoimmune response (9). In type I and II systems, foreign DNA targets that contain adjacent PAM sequences are [...]

Author(s): Paul W. Sternberg (corresponding author) [1] Forty years ago, John Sulston and Robert Horvitz [1] published a landmark paper that launched the nematode worm Caenorhabditis elegans on course to [...]

Genotyping of microorganisms typically relies on comparison of genomic features (e.g., fragment size, repeats, single-nucleotide polymorphisms [SNPs]) between strains and/or against a database of feature profiles (e.g., PulseNET and mlst.net) [...]

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated enzyme Cas9 is an RNA-guided endonuclease that uses RNA-DNA base-pairing to target foreign DNA in bacteria. Cas9-guide RNA complexes are also effective genome engineering agents in animals and plants. Here we use single-molecule and bulk biochemical experiments to determine how Cas9-RNA interrogates DNA to find specific cleavage sites. We show that both binding and cleavage of DNA by Cas9-RNA require recognition of a short trinucleotide protospacer adjacent motif (PAM). Non-target DNA binding affinity scales with PAM density, and sequences fully complementary to the guide RNA but lacking a nearby PAM are ignored by Cas9-RNA. Competition assays provide evidence that DNA strand separation and RNA-DNA hetero-duplex formation initiate at the PAM and proceed directionally towards the distal end of the target sequence. Furthermore, PAM interactions trigger Cas9 catalytic activity. These results reveal how Cas9 uses PAM recognition to quickly identify potential target sites while scanning large DNA molecules, and to regulate scission of double-stranded DNA., RNA-mediated adaptive immune systems in bacteria and archaea rely on CRISPRs and CRISPR-associated (Cas) proteins to provide protection from invading viruses and plasmids (1). Bacteria harbouring CRISPR-Cas loci respond to [...]

Brucellae are worldwide bacterial pathogens of livestock and wildlife, but phylogenetic reconstructions have been challenging due to limited genetic diversity. We assessed the taxonomic and evolutionary relationships of five Brucella species--Brucella abortus, B. melitensis, B. suis, B. canis, and B. ovis--using whole-genome comparisons. We developed a phylogeny using single nucleotide polymorphisms (SNPs) from 13 genomes and rooted the tree using the closely related soil bacterium and opportunistic human pathogen, Ochrobactrum anthropi. Whole-genome sequencing and a SNP-based approach provided the requisite level of genetic detail to resolve species in the highly conserved brucellae. Comparisons among the Brucella genomes revealed 20,154 orthologous SNPs that were shared in all genomes. Rooting with Ochrobactrum anthropi reveals that the B. ovis lineage is basal to the rest of the Brucella lineage. We found that B. suis is a highly divergent clade with extensive intraspecific genetic diversity. Furthermore, B. suis was determined to be paraphyletic in our analyses, only forming a monophyletic clade when the B. canis genome was included. Using a molecular clock with these data suggests that most Brucella species diverged from their common B. ovis ancestor in the past 86,000 to 296,000 years, which precedes the domestication of their livestock hosts. Detailed knowledge of the Brucella phylogeny will lead to an improved understanding of the ecology, evolutionary history, and host relationships for this genus and can be used for determining appropriate genotyping approaches for rapid detection and diagnostic assays for molecular epidemiological and clinical studies.

Francisella tularensis contains several highly pathogenic subspecies, including Francisella tularensis subsp. holarctica, whose distribution is circumpolar in the northern hemisphere. The phylogeography of these subspecies and their subclades was examined using whole-genome single nucleotide polymorphism (SNP) analysis, high-density microarray SNP genotyping, and real-time-PCR-based canonical SNP (canSNP) assays. Almost 30,000 SNPs were identified among 13 whole genomes for phylogenetic analysis. We selected 1,655 SNPs to genotype 95 isolates on a high-density microarray platform. Finally, 23 clade- and subclade-specific canSNPs were identified and used to genotype 496 isolates to establish global geographic genetic patterns. We confirm previous findings concerning the four subspecies and two Francisella tularensis subsp. tularensis subpopulations and identify additional structure within these groups. We identify 11 subclades within F. tularensis subsp. holarctica, including a new, genetically distinct subclade that appears intermediate between Japanese F. tularensis subsp. holarctica isolates and the common F. tularensis subsp. holarctica isolates associated with the radiation event (the B radiation) wherein this subspecies spread throughout the northern hemisphere. Phylogenetic analyses suggest a North American origin for this B-radiation clade and multiple dispersal events between North America and Eurasia. These findings indicate a complex transmission history for F. tularensis subsp. holarctica.

AN INTELLIGENT ANALYSIS OF HUMAN INTELLIGENCE By Earl Hunt Cambridge, England: Cambridge University Press, 2011. 507 pp. Paper, $59. Readers approaching retirement age, take hope! Earl Hunt's book, like Jack [...]