Explore the vast range of titles available.

The CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) systems are immunity systems that are present in many bacteria and archaea. Here, Koonin and colleagues present a new classification of these systems and introduce a new nomenclature of the genes in the CRISPR– cas loci that better reflects the relationships between the proteins. The CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) modules are adaptive immunity systems that are present in many archaea and bacteria. These defence systems are encoded by operons that have an extraordinarily diverse architecture and a high rate of evolution for both the cas genes and the unique spacer content. Here, we provide an updated analysis of the evolutionary relationships between CRISPR–Cas systems and Cas proteins. Three major types of CRISPR–Cas system are delineated, with a further division into several subtypes and a few chimeric variants. Given the complexity of the genomic architectures and the extremely dynamic evolution of the CRISPR–Cas systems, a unified classification of these systems should be based on multiple criteria. Accordingly, we propose a 'polythetic' classification that integrates the phylogenies of the most common cas genes, the sequence and organization of the CRISPR repeats and the architecture of the CRISPR– cas loci.

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci ( P  < 5 × 10 −8 ), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis. A genome-wide association study and Metabochip meta-analysis of body mass index (BMI) detects 97 BMI-associated loci, of which 56 were novel, and many loci have effects on other metabolic phenotypes; pathway analyses implicate the central nervous system in obesity susceptibility and new pathways such as those related to synaptic function, energy metabolism, lipid biology and adipogenesis. Genetic correlates of obesity In the second of two Articles in this issue from the GIANT Consortium, Elizabeth Speliotes and collegues conducted a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), commonly used to define obesity and assess adiposity, to find 97 BMI-associated loci, of which 56 were novel. Many of these loci have significant effects on other metabolic phenotypes. The 97 loci account for about 2.7% of BMI variation, and genome-wide estimates suggest common variation accounts for more than 20% of BMI variation. Pathway analyses implicate the central nervous system in obesity susceptibility including synaptic function, glutamate signaling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Purpose Numerous studies have examined factors influencing electronic word of mouth (eWOM) providing behaviour. The volume of extant research and inconsistency in some of the findings makes it useful to develop an all-encompassing model synthesising results. Therefore, the purpose of this study is to synthesise findings from existing studies on eWOM by using meta-analysis, which will help to reconcile conflicting findings of factors affecting consumers’ intention to engage in eWOM communications. Design/methodology/approach The findings from 51 studies were used for meta-analysis, which was undertaken using comprehensive meta-analysis software. Findings Factors affecting eWOM providing behaviour were divided into four groups: personal conditions, social conditions, perceptual conditions and consumption-based conditions. The results of the meta-analysis showed that out of 20 identified relationships, 16 were found to be significant (opinion seeking, information usefulness, trust in web eWOM services, economic incentive, customer satisfaction, loyalty, brand attitude, altruism, affective commitment, normative commitment, opinion leadership, self-enhancement, information influence, tie strength, homophily and community identity). Research limitations/implications One of the limitations of this study is that the studies for this research were collected the only form from Web of Science, Scopus and Business Source such as databases, which result in a limited number of studies available for weight and meta-analysis. A wider range of databases should be used by future research. Also, this study only considered quantitative studies and excluded qualitative studies. Thus, future studies could include both types of studies in the meta-analysis. Practical implications By focussing on the best predictors of intention to provide eWOM communications (e.g. self-enhancement and trust in web eWOM services) managers can improve reader engagement and information assimilation. Knowing motivations to engage in eWOM helps platform operators design their service in a more customer-oriented way. By better understanding motivations to engage in eWOM communications marketers and researchers can influence individuals’ online information assimilation which can affect consumer purchase decisions, customer loyalty and consumer commitment to the community. Originality/value Applying meta-analysis helped the reconciliation of conflicting findings, enabled investigation of the strengths of the relationships between motivations and eWOM providing behaviour and offered a consolidated view. The results of this study facilitate the advancement of current knowledge of information dissemination on the internet, which can influence consumer purchase intention and loyalty.

Although it is widely believed that early vertebrate evolution was shaped by ancient whole-genome duplications, the number, timing and mechanism of these events remain elusive. Here, we infer the history of vertebrates through genomic comparisons with a new chromosome-scale sequence of the invertebrate chordate amphioxus. We show how the karyotypes of amphioxus and diverse vertebrates are derived from 17 ancestral chordate linkage groups (and 19 ancestral bilaterian groups) by fusion, rearrangement and duplication. We resolve two distinct ancient duplications based on patterns of chromosomal conserved synteny. All extant vertebrates share the first duplication, which occurred in the mid/late Cambrian by autotetraploidization (that is, direct genome doubling). In contrast, the second duplication is found only in jawed vertebrates and occurred in the mid–late Ordovician by allotetraploidization (that is, genome duplication following interspecific hybridization) from two now-extinct progenitors. This complex genomic history parallels the diversification of vertebrate lineages in the fossil record. Genomic comparisons with a new amphioxus chromosome-scale genome assembly reveal details of the early evolution of vertebrate genomes.

Background: Informal caregivers are those providing care, which exceeds that which is typically provided, to a relative or friend with care needs. Informal caregiving constitutes the backbone of a society's care supply and with ageing populations the need for informal care is growing. We know little as to why caregivers start caring and continue doing so, yet understanding of motivations and willingness to provide care is important if informal caregivers are to be supported. However, both motivations and willingness are inconsistently defined making it difficult to compare the empirical findings that do exist. Methods: This paper reviews and synthesises thinking about the theoretical constructs of motivations to provide care and willingness to perform informal care, and presents those in relation to existing theoretical and empirical literature. Results and Conclusions: Theoretical reflections based on various motivational frameworks and available empirical data are presented to illustrate that: caregiving motivations should be conceptualised as multifaceted and multiply determined; intrinsic and extrinsic motivations should not be treated as antagonistic and can occur simultaneously; the commonly applied model of extrinsic/intrinsic motivations is oversimplified and omits consideration of the diversity of caregiver motives; other motivational models can be discerned in the context of the empirical research; there are differences between motivations and willingness to provide care with the latter being more consequent to the motives; both should be considered dynamic in nature; and finally, that the two constructs may not inevitably lead to actual caregiver behaviour. The implications of these theoretical reflections for methodology and research as well as their relevance for practice and policy are indicated.

Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone which is essential in eukaryotes. It is required for the activation and stabilization of a wide variety of client proteins and many of them are involved in important cellular pathways. Since Hsp90 affects numerous physiological processes such as signal transduction, intracellular transport, and protein degradation, it became an interesting target for cancer therapy. Structurally, Hsp90 is a flexible dimeric protein composed of three different domains which adopt structurally distinct conformations. ATP binding triggers directionality in these conformational changes and leads to a more compact state. To achieve its function, Hsp90 works together with a large group of cofactors, termed co-chaperones. Co-chaperones form defined binary or ternary complexes with Hsp90, which facilitate the maturation of client proteins. In addition, posttranslational modifications of Hsp90, such as phosphorylation and acetylation, provide another level of regulation. They influence the conformational cycle, co-chaperone interaction, and inter-domain communications. In this review, we discuss the recent progress made in understanding the Hsp90 machinery.

Psychological interventions for post-traumatic stress disorder (PTSD) are not always effective and can leave some individuals with enduring symptoms. Little is known about factors that are associated with better or worse treatment outcome. Our objective was to address this gap. We undertook a systematic review following Cochrane Collaboration Guidelines. We included 126 randomized controlled trials (RCTs) of psychological interventions for PTSD and examined factors that were associated with treatment outcome, in terms of severity of PTSD symptoms post-treatment, and recovery or remission. Associations were neither consistent nor strong. Two factors were associated with smaller reductions in severity of PTSD symptoms post-treatment: comorbid diagnosis of depression, and higher PTSD symptom severity at baseline assessment. Higher education, adherence to homework and experience of a more recent trauma were associated with better treatment outcome. Identifying and understanding why certain factors are associated with treatment outcome is vital to determine which individuals are most likely to benefit from particular treatments and to develop more effective treatments in the future. There is an urgent need for consistent and standardized reporting of factors associated with treatment outcome in all clinical trials.

Prokaryotes acquire virus resistance by integrating short fragments of viral nucleic acid into clusters of regularly interspaced short palindromic repeats (CRISPRs). Here we show how virus-derived sequences contained in CRISPRs are used by CRISPR-associated (Cas) proteins from the host to mediate an antiviral response that counteracts infection. After transcription of the CRISPR, a complex of Cas proteins termed Cascade cleaves a CRISPR RNA precursor in each repeat and retains the cleavage products containing the virus-derived sequence. Assisted by the helicase Cas3, these mature CRISPR RNAs then serve as small guide RNAs that enable Cascade to interfere with virus proliferation. Our results demonstrate that the formation of mature guide RNAs by the CRISPR RNA endonuclease subunit of Cascade is a mechanistic requirement for antiviral defense.

Bacteriophages typically have small genomes 1 and depend on their bacterial hosts for replication 2 . Here we sequenced DNA from diverse ecosystems and found hundreds of phage genomes with lengths of more than 200 kilobases (kb), including a genome of 735 kb, which is—to our knowledge—the largest phage genome to be described to date. Thirty-five genomes were manually curated to completion (circular and no gaps). Expanded genetic repertoires include diverse and previously undescribed CRISPR–Cas systems, transfer RNAs (tRNAs), tRNA synthetases, tRNA-modification enzymes, translation-initiation and elongation factors, and ribosomal proteins. The CRISPR–Cas systems of phages have the capacity to silence host transcription factors and translational genes, potentially as part of a larger interaction network that intercepts translation to redirect biosynthesis to phage-encoded functions. In addition, some phages may repurpose bacterial CRISPR–Cas systems to eliminate competing phages. We phylogenetically define the major clades of huge phages from human and other animal microbiomes, as well as from oceans, lakes, sediments, soils and the built environment. We conclude that the large gene inventories of huge phages reflect a conserved biological strategy, and that the phages are distributed across a broad bacterial host range and across Earth’s ecosystems. Genomic analyses of major clades of huge phages sampled from across Earth’s ecosystems show that they have diverse genetic inventories, including a variety of CRISPR–Cas systems and translation-relevant genes.

Synthetic Aperture Radar (SAR) observations are widely used in emergency response for flood mapping and monitoring. However, the current operational services are mainly focused on flood in rural areas and flooded urban areas are less considered. In practice, urban flood mapping is challenging due to the complicated backscattering mechanisms in urban environments and in addition to SAR intensity other information is required. This paper introduces an unsupervised method for flood detection in urban areas by synergistically using SAR intensity and interferometric coherence under the Bayesian network fusion framework. It leverages multi-temporal intensity and coherence conjunctively to extract flood information of varying flooded landscapes. The proposed method is tested on the Houston (US) 2017 flood event with Sentinel-1 data and Joso (Japan) 2015 flood event with ALOS-2/PALSAR-2 data. The flood maps produced by the fusion of intensity and coherence and intensity alone are validated by comparison against high-resolution aerial photographs. The results show an overall accuracy of 94.5% (93.7%) and a kappa coefficient of 0.68 (0.60) for the Houston case, and an overall accuracy of 89.6% (86.0%) and a kappa coefficient of 0.72 (0.61) for the Joso case with the fusion of intensity and coherence (only intensity). The experiments demonstrate that coherence provides valuable information in addition to intensity in urban flood mapping and the proposed method could be a useful tool for urban flood mapping tasks.