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Auxin-inducible degrons are a chemical genetic tool for targeted protein degradation and are widely used to study protein function in cultured mammalian cells. Here, we develop CRISPR-engineered mouse lines that enable rapid and highly specific degradation of tagged endogenous proteins in vivo. Most but not all cell types are competent for degradation. Using mouse genetics, we show that degradation kinetics depend upon the dose of the tagged protein, ligand, and the E3 ligase subunit Tir1. Rapid degradation of condensin I and condensin II – two essential regulators of mitotic chromosome structure - revealed that both complexes are individually required for cell division in precursor lymphocytes, but not in their differentiated peripheral lymphocyte derivatives. This generalisable approach provides unprecedented temporal control over the dose of endogenous proteins in mouse models, with implications for studying essential biological pathways and modelling drug activity in mammalian tissues.HighlightsAuxin-inducible degradation of endogenously tagged proteins in living mice and a range of primary cells.Most but not all cell types are competent for degradationDosage of the tagged protein, E3 ligase substrate receptor and ligand can all determine degradation kineticsRapid degradation of condensin subunits in lymphocytes reveals stage-specific requirements during cell division

Background and ObjectivesEEG is widely recommended for status epilepticus (SE) management. However, EEG access and use across the United States is poorly characterized. We aimed to evaluate changes in inpatient EEG access over time and whether availability of EEG is associated with interhospital transfers for patients hospitalized with SE.MethodsWe performed a cross-sectional study using data available in the National Inpatient Sample data set from 2012 to 2018. We identified hospitals that used continuous or routine EEG during at least 1 seizure-related hospitalization in a given year using ICD-9 and ICD-10 procedure codes and defined these hospitals as EEG capable. We examined annual change in the proportion of hospitals that were EEG capable during the study period, compared characteristics of hospitals that were EEG capable with those that were not, and fit multivariable logistic regression models to determine whether hospital EEG capability was associated with likelihood of interhospital transfer.ResultsAmong 4,550 hospitals in 2018, 1,241 (27.3%) were EEG capable. Of these, 1,188 hospitals (95.7%) were in urban settings. From 2012 to 2018, the proportion of hospitals that were EEG capable increased in urban settings (30.5%–41.1%, Mann-Kendall [M-K] testp< 0.001) and decreased in rural settings (4.0%–3.2%, M-Kp= 0.026). Among 130,580 patients hospitalized with SE, 80,725 (61.8%) presented directly to an EEG-capable hospital. However, EEG use during hospitalization varied from 8% to 98%. Initial admission to a hospital without EEG capability was associated with 22% increased likelihood of interhospital transfer (adjusted RR 1.22, [95% CI, 1.09–1.37];p< 0.01). Among those hospitalized at an EEG-capable hospital, patients admitted to hospitals in the lowest quintile of EEG volume were more than 2 times more likely to undergo interhospital transfer (adjusted RR 2.22, [95% CI 1.65–2.93];p< 0.001).DiscussionA minority of hospitals are EEG capable yet care for most patients with SE. Inpatient EEG use, however, varies widely among EEG-capable hospitals, and lack of inpatient EEG access is associated with interhospital transfer. Given the high incidence and cost of SE, there is a need to better understand the importance and use of EEG in this patient population to further organize inpatient epilepsy systems of care to optimize outcomes.

Withdrawal Note:The authors have withdrawn their manuscript due to the discovery of artifacts that call into question key findings from the study. Both artifacts originate from cell-type differences that arose during sample processing, creating the impression that non-SMC subunits of condensin proteins were present at substantially higher levels in thymic T cells compared to bone marrow B cells or erythroblast cells. Based on data collected since the preprint was submitted, we no longer believe this to be true. The experimental artifacts do not affect the data contributed by the Papadopoulos laboratory (Figure 4).The authors wish to make it clear that all data and experimental protocols in the original manuscript were accurately reported, and that the experimental artifacts which affect data interpretation were discovered during internal review, independently of peer review, and are being reported at the authors’ own instigation. They do not, to our knowledge, affect the interpretation of data from any other published work.Due to the issues outlined above, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

Summary Sustainable cropping systems are needed for future food security. One aspect of sustainable cropping is to manage for desirable grain quality of crops including seed size, protein, oil and metabolite composition. Plant ecology theory on niche relationships and interspecific competition predicts that subordinate species mixtures (i.e. weed species) will affect dominant (i.e. crop) species offspring quality. Beyond individual weed species effects on crop quality, we hypothesise that the integrated effect of weed mixtures will be influenced by taxonomic, functional trait and phylogenetic diversity. Reviewing Glycine max (soybean)–weed systems, we show a complex relationship between the weed community and G. max seed protein, oil, mean seed mass and physiological markers (relative water content, trigonelline leaf content, fluorescence, foliar Cu, Fe and Zn). Increased levels of weed competition led to increased seed protein, at the expense of seed oil. Synthesis. We propose that research on interspecific relationships between crops and weeds consider weed species diversity, weed functional traits associated with the Leaf-Height-Seed strategy and phylogenetic relationships to identify weed mixtures (either sown or manipulated through herbicide control) best suited to minimise their detrimental effects on yield while maximising crop quality as part of sustainable cropping systems.

Objective:To prospectively assess treatment outcomes of chronic rhinosinusitis patients undergoing functional endoscopic sinus surgery and post-operative medical treatment over a prolonged follow-up period.Methods:Patients undergoing functional endoscopic sinus surgery in the tertiary referral practice of a single surgeon were studied prospectively. Symptoms were scored by patients pre-operatively and over a minimum follow-up period of 12 months.Results:The study comprised 200 non-consecutive patients. The median pre-operative symptom score was 16 (out of a maximum of 25) (95 per cent confidence interval = 15 to 17). Symptom scores reduced to a median of 7 (95 per cent confidence interval = 6 to 8) after 12 months of follow up (p< 0.0001). The median symptom score improved for all symptoms and across all patient subgroups.Conclusion:Extensive functional endoscopic sinus surgery offers significant and durable symptom improvement in patients with chronic rhinosinusitis refractory to medical treatment. This improvement extends to all patient subgroups. Prolonged medical therapy is recommended after functional endoscopic sinus surgery.

Stevphen Shukaitis has produced an interesting text by situating a strategic conversation between artistic avant-gardes and autonomist political movements. He begins with a plea for rethinking strategy, and not just questions of tactics, in seeking radical aesthetic and socio-political change.

SummaryMosses (Bryophyta) are a key group occupying important phylogenetic position for understanding land plant (embryophyte) evolution. The class Bryopsida represents the most diversified lineage and contains more than 95% of the modern mosses, whereas the other classes are by nature species-poor. The phylogeny of mosses remains elusive at present.Recurrent whole genome duplications have shaped the evolution trajectory of angiosperms, but little is known about the genome evolutionary history in mosses. It remains to be answered if there existed a historical genome duplication event associated with the species radiation of class Bryopsida.Here, the high-confidence moss phylogeny was generated covering major moss lineages. Two episodes of ancient genomic duplication events were elucidated by phylogenomic analyses, one in the ancestry of all mosses and another before the separation of the Bryopsida, Polytrichopsida and Tetraphidopsida, with estimated ages of the gene duplications clustered around 329 and 182 million year ago, respectively.The third episode of polyploidy event (termed ψ) was tightly associated with the early diversification of Bryopsida with an estimated age of ~87 million years. By scrutinizing the phylogenetic timing of duplicated syntelogs in Physcomitrella patens, the WGD1 and WGD2 events were confidently re-recognized as the ψ event and the Funarioideae duplication event (~65 mya), respectively. Together, our findings unveiled four episodes of polyploidy events in the evolutionary past of Physcomitrella patens.

ObjectiveTo examine the impact of temporal bone virtual reality surgical simulator use in the undergraduate otorhinolaryngology curriculum.MethodsMedical students attended a workshop involving the use of a temporal bone virtual reality surgical simulator. Students completed a pre-workshop questionnaire on career interests. A post-workshop questionnaire evaluated the perceived usefulness and enjoyment of the virtual reality surgical simulator experience, and assessed changes in their interest in ENT.ResultsThirty-two fifth-year University of Auckland medical students were recruited. The majority of students (53.1 per cent) had already chosen their career path. The simulator experience was useful for: stimulating thoughts around career plans (71.9 per cent), providing hands-on experience (93.8 per cent) and teaching disease processes (93.8 per cent). After the workshop, 53.1 per cent of students were more interested in a career in ENT.ConclusionVirtual reality may be a fun and engaging way of teaching ENT. Furthermore, it could help guide student career planning.

Bryum argenteum is a desert moss which shows tolerance to the desert environment and is emerging as a good plant material for identification of stress-related genes. AP2/ERF transcription factor family plays important roles in plant responses to biotic and abiotic stresses. AP2/ERF genes have been identified and extensively studied in many plants, while they are rarely studied in moss. In the present study, we identified 83 AP2/ERF genes based on the comprehensive dehydrationrehydration transcriptomic atlas of B. argenteum. BaAP2/ERF genes can be classified into five families, including 11 AP2s, 43 DREBs, 26 ERFs, 1 RAV, and 2 Soloists. RNA-seq data showed that 83 BaAP2/ERFs exhibited elevated transcript abundances during dehydration&ndash, rehydration process. We used RT-qPCR to validate the expression profiles of 12 representative BaAP2/ERFs and confirmed the expression trends using RNA-seq data. Eight out of 12 BaAP2/ERFs demonstrated transactivation activities. Seven BaAP2/ERFs enhanced salt and osmotic stress tolerances of yeast. This is the first study to provide detailed information on the identification, classification, and functional analysis of the AP2/ERFs in B. argenteum. This study will lay the foundation for the further functional analysis of these genes in plants, as well as provide greater insights into the molecular mechanisms of abiotic stress tolerance of B. argenteum.

SummaryCondensin complexes compact and disentangle chromosomes in preparation for cell division. Commercially available antibodies raised against condensin subunits have been widely used to characterise their cellular interactome. Here we have assessed the specificity of a polyclonal antibody (Bethyl A302-276A) that is commonly used as a probe for NCAPH2, the kleisin subunit of condensin II, in mammalian cells. We find that, in addition to its intended target, this antibody cross-reacts with one or more components of the SWI/SNF family of chromatin remodelling complexes in an NCAPH2-independent manner. This cross-reactivity with an abundant chromatin-associated factor is likely to affect the interpretation of protein and chromatin immunoprecipitation experiments that make use of this antibody probe.

Chromosomal instability is a hallmark of cancer, but mitotic regulators are rarely mutated in tumors. Mutations in the condensin complexes, which restructure chromosomes to facilitate segregation during mitosis, are significantly enriched in cancer genomes, but experimental evidence implicating condensin dysfunction in tumorigenesis is lacking. We report that mice inheriting missense mutations in a condensin II subunit (Caph2nes) develop T-cell lymphoma. Before tumors develop, we found that the same Caph2 mutation impairs ploidy maintenance to a different extent in different hematopoietic cell types, with ploidy most severely perturbed at the CD4+CD8+ T-cell stage from which tumors initiate. Premalignant CD4+CD8+ T cells show persistent catenations during chromosome segregation, triggering DNA damage in diploid daughter cells and elevated ploidy. Genome sequencing revealed that Caph2 single-mutant tumors are near diploid but carry deletions spanning tumor suppressor genes, whereas P53 inactivation allowed Caph2 mutant cells with whole-chromosome gains and structural rearrangements to form highly aggressive disease. Together, our data challenge the view that mitotic chromosome formation is an invariant process during development and provide evidence that defective mitotic chromosome structure can promote tumorigenesis.

A major obstacle to a broadly neutralizing antibody (bnAb)–based HIV vaccine is the activation of appropriate B cell precursors. Germline-targeting immunogens must be capable of priming rare bnAb precursors in the physiological setting. We tested the ability of the VRC01-class bnAb germline-targeting immunogen eOD-GT8 60mer (60-subunit self-assembling nanoparticle) to activate appropriate precursors in mice transgenic for human immunoglobulin (Ig) loci. Despite an average frequency of, at most, about one VRC01-class precursor per mouse, we found that at least 29% of singly immunized mice produced a VRC01-class memory response, suggesting that priming generally succeeded when at least one precursor was present. The results demonstrate the feasibility of using germline targeting to prime specific and exceedingly rare bnAb-precursor B cells within a humanlike repertoire.

Syntrichia caninervis is desiccation-tolerant moss and a dominant species in biological soil crusts in the Gurbantunggut desert of Northwestern China. S. caninervis is being developed as a model moss for studying the molecular mechanisms of desiccation tolerance (DT) and as a source for stress-related genes germplasm. Aldehyde dehydrogenases (ALDHs) are a set of NAD (P)+ dependent enzymes that oxidize a wide range of endogenous and exogenous aromatic and aliphatic aldehydes into their corresponding non-toxic carboxylic acids. In the current study, we identified 15 ALDH genes from the moss S.caninervis, grouped them into eleven families based upon clearly established criteria. As determined by RT-qPCR, transcript abundance of ScALDH genes respond to drought, salinity, cold, and/or ABA treatment. ScALDH5F, ScALDH6B1, ScALDH7B1, ScALDH11A1 and ScALDH21A1 exhibited consistent up-regulation as compared to other transcripts. We selected four genes (ScALDH2B2, ScALDH10A1, ScALDH11A1 and ScALDH21A1) based upon sequence characteristics and qRT-PCR profiles, and subsequently cloned and transformed to E. coli strain where the transgenes conferred varying degree of drought and salt tolerance. The four purified ScALDH proteins indicated enzyme activities with aldehyde of C6-C9 carbon chain as substrates were more suitable than that of C1-C2 carbon chain, especially unsaturated aldehyde, all have their own special substrates.

CRISPR-Cas9 genome editing occurs in the context of chromatin, which is heterogeneous in structure and function across the genome. Chromatin heterogeneity is thought to affect genome editing efficiency, but this has been challenging to quantify due to the presence of confounding variables. Here, we develop a method that exploits the allele-specific chromatin status of imprinted genes in order to address this problem. Because maternal and paternal alleles of imprinted genes have identical DNA sequence and are situated in the same nucleus, allele-specific differences in the frequency and spectrum of Cas9-induced mutations can be attributed unequivocally to epigenetic mechanisms. We found that heterochromatin can impede mutagenesis, but to a degree that depends on other key experimental parameters. Mutagenesis was impeded by up to 7-fold when Cas9 exposure was brief and when intracellular Cas9 expression was low. Surprisingly, the outcome of mutagenic DNA repair was independent of chromatin state, with similar efficiencies of homology directed repair and deletion spectra on maternal and paternal chromosomes. Combined, our data show that heterochromatin imposes a permeable barrier that influences the kinetics, but not the endpoint of CRISPR-Cas9 genome editing, and suggest that therapeutic applications involving low-level Cas9 exposure will be particularly affected by chromatin status.

Background Facilitated by the rapid progress of sequencing technology, comparative genomic studies in plants have unveiled recurrent whole genome duplication (i.e. polyploidization) events throughout plant evolution. The evolutionary past of plant genes should be analyzed in a background of recurrent polyploidy events in distinctive plant lineages. The Vascular Plant One Zinc-finger (VOZ) gene family encode transcription factors associated with a number of important traits including control of flowering time and photoperiodic pathways, but the evolutionary trajectory of this gene family remains uncharacterized. Results In this study, we deciphered the evolutionary history of the VOZ gene family by analyses of 107 VOZ genes in 46 plant genomes using integrated methods: phylogenic reconstruction, Ks-based age estimation and genomic synteny comparisons. By scrutinizing the VOZ gene family phylogeny the core eudicot γ event was well circumscribed, and relics of the precommelinid τ duplication event were detected by incorporating genes from oil palm and banana. The more recent T and ρ polyploidy events, closely coincident with the species diversification in Solanaceae and Poaceae, respectively, were also identified. Other important polyploidy events captured included the “salicoid” event in poplar and willow, the “early legume” and “soybean specific” events in soybean, as well as the recent polyploidy event in Physcomitrella patens. Although a small transcription factor gene family, the evolutionary history of VOZ genes provided an outstanding record of polyploidy events in plants. The evolutionary past of VOZ gene family demonstrated a close correlation with critical plant polyploidy events which generated species diversification and provided answer to Darwin’s “abominable mystery”. Conclusions We deciphered the evolutionary history of VOZ transcription factor family in plants and ancestral polyploidy events in plants were recapitulated simultaneously. This analysis allowed for the generation of an idealized plant gene tree demonstrating distinctive retention and fractionation patterns following polyploidy events. Electronic supplementary material The online version of this article (10.1186/s12870-018-1437-8) contains supplementary material, which is available to authorized users.

Background: Chronic rhinosinusitis (CRS) is highly prevalent in cystic fibrosis (CF) patients, in whom a close correlation exists between the microbiology of the upper and lower respiratory tracts. We have reported intramucosal bacterial microcolonies in the sinus mucosa from idiopathic CRS patients and have made observations suggesting that these may result from mucosal immunotolerance secondary to altered macrophage function. In this study,wesoughttodeterminewhetherintramucosalmicrocoloniesexistinthemucosaofCFpatientswithCRS,andto investigate the associated mucosal immunology. Methods: Mucus swabs and tissue biopsies were taken from 9 patients with CF undergoing functional endoscopic sinus surgery (FESS) for CRS, 11 with idiopathic CRS undergoing FESS, and 9 with normal sinuses having transnasal pituitary surgery. Microbiology samples were taken for culture and intramucosal microcolonies were sought using Gram staining. Mucosal immune cells were identified using fluorescent immunohistochemistry. Results: Positive culture rates were similar between CRS patients and controls, but there were significantly more intramucosal microcolonies in the CRS groups (8/9 CFCRS, 7/11 CRS), compared to controls (1/9). Furthermore, the biodensity of intramucosal microcolonies was significantly higher in CF-CRS than idiopathic CRS. Mirroring the microbiological observations, the number of CD163+ macrophages was significantly increased in CF-CRS compared to idiopathic CRS (p = 0.03). Conclusion: Intramucosal bacteria exist within the sinus mucosa of patients with CF, and in significantly greater numbers than in idiopathic CRS patients. We speculate that intramucosal microcolonies may also exist in the lower respiratory tract mucosa in CF and play a role in disease recalcitrance. C � 2015 ARS-AAOA, LLC.

Background We have detected intramucosal bacteria within the sinus mucosa of patients with chronic rhinosinusitis (CRS), but our attempts at characterizing these did not yield any discernible genotypic or phenotypic differences from surface bacteria. We hypothesized that the presence of intramucosal microcolonies reflected host mucosal immune dysfunction. This study characterizes the activation status of T cells, B cells, and macrophages in the sinus mucosa of patients with CRS and controls and determines the impact of bacteria on mucosal immunology. Methods Swabs and mucosal biopsy specimens were taken from 27 patients with CRS undergoing sinus surgery and 9 patients with normal sinuses having transnasal pituitary surgery. Microcolonies were detected using Gram staining, and the immune cells were characterized by immunohistochemical techniques. Results Swab culture rates for Staphylococcus aureus were similar between CRS and controls. However, there were significantly more intramucosal microcolonies in CRS (59% versus 11%) than in controls (p = 0.02). There were significantly more immune cells in CRS. Percentage of activated T and B cells were similar between CRS and controls, but there were significantly more CD163+ M2 macrophages in patients with CRS (p = 0.0004). Furthermore, percentage of CD163+ macrophages showed a positive correlation with disease severity. The presence of bacteria had no impact on immunology or disease severity. Conclusion Tolerance of intramucosal microcolonies in CRS may reflect altered macrophage function in the host mucosa. The clinical severity of CRS is also dependent on the host mucosa immune dysfunction, rather than the presence of intramucosal microcolonies.

The desiccation tolerant bryophyte Bryum argenteum is an important component of desert biological soil crusts (BSCs) and is emerging as a model system for studying vegetative desiccation tolerance. Here we present and analyze the hydration-dehydration-rehydration transcriptomes in B. argenteum to establish a desiccation-tolerance transcriptomic atlas. B. argenteum gametophores representing five different hydration stages (hydrated (H0), dehydrated for 2 h (D2), 24 h (D24), then rehydrated for 2 h (R2) and 48 h (R48)), were sampled for transcriptome analyses. Illumina high throughput RNA-Seq technology was employed and generated more than 488.46 million reads. An in-house de novo transcriptome assembly optimization pipeline based on Trinity assembler was developed to obtain a reference Hydration-Dehydration-Rehydration (H-D-R) transcriptome comprising of 76,206 transcripts, with an N50 of 2,016 bp and average length of 1,222 bp. Comprehensive transcription factor (TF) annotation discovered 978 TFs in 62 families, among which 404 TFs within 40 families were differentially expressed upon dehydration-rehydration. Pfam term enrichment analysis revealed 172 protein families/domains were significantly associated with the H-D-R cycle and confirmed early rehydration (i.e. the R2 stage) as exhibiting the maximum stress-induced changes in gene expression.

Salinity is a major limitation factor for crop productivity worldwide. DREB transcription factors broadly participate in plant stress response and have been extensively identified in a wide variety of plants. In this study, we characterized and analyzed the function of a novel A-5 type DREB gene ScDREB8 from the desiccation tolerant moss Syntrichia caninervis. Yeast one-hybrid experiment showed that ScDREB8 had no transactivation activity. Transient expression assay in onion epidermal cells revealed that ScDREB8 is distributed throughout the cell with no apparent specificity. Overexpression of ScDREB8 significantly increased the germination rate of Arabidopsis under salt stress and improved the salt tolerance of Arabidopsis at the seedling stage by up-regulating the expression of downstream stress-related genes and improving ROS scavenging ability. ScDREB8 is a promising candidate gene for improving crop salt stress and will provide greater insight to the molecular mechanism of stress tolerance of A-5 type DREB proteins.

Sean Johnson Andrews has produced an engaging text of multifaceted value. His work, particularly the opening chapters, provides a concise history of the Birmingham Centre for Contemporary Cultural Studies (CCCS), the (early) Frankfurt School Critical Theory, and the Political Economy of Communication (PEC). Although the histories and notable figureheads of these schools will be broadly familiar to most scholars working in the realm of cultural studies, these opening chapters would be an excellent introduction to the field for either a general readership or students. Indeed, this would make a good textbook in many contexts.

APETALA2/Ethylene Responsive Factor (AP2/ERF) is a large family of plant transcription factors which play important roles in the control of plant metabolism and development as well as responses to various biotic and abiotic stresses. The desert moss Syntrichia caninervis, due to its robust and comprehensive stress tolerance, is a promising organism for the identification of stress-related genes. Using S. caninervis transcriptome data, 80 AP2/ERF unigenes were identified by HMM modeling and BLASTP searching. Based on the number of AP2 domains, multiple sequence alignment, motif analysis, and gene tree construction, ScAP2/ERF genes were classified into three main subfamilies (including 5 AP2 gene members, 72 ERF gene members, and 1 RAV member) and two Soloist members. We found that the ratio for each subfamily was constant between S. caninervis and the model moss Physcomitrella patens, however, as compared to the angiosperm Arabidopsis, the percentage of ERF subfamily members in both moss species were greatly expanded, while the members of the AP2 and RAV subfamilies were reduced accordingly. The amino acid composition of the AP2 domain of ScAP2/ERFs was conserved as compared with Arabidopsis. Interestingly, most of the identified DREB genes in S. caninervis belonged to the A-5 group which play important roles in stress responses and are rarely reported in the literature. Expression profile analysis of ScDREB genes showed different gene expression patterns under dehydration and rehydration; the majority of ScDREB genes demonstrated a stronger response to dehydration relative to rehydration indicating that ScDREB may play an important role in dehydrated moss tissues. To our knowledge, this is the first study to detail the identification and characterization of the AP2/ERF gene family in a desert moss. Further, this study will lay the foundation for further functional analysis of these genes, provide greater insight to the stress tolerance mechanisms in S. caninervis and provide a reference for AP2/ERF gene family classification in other moss species.

Drought and salinity are major factors limiting crop productivity worldwide. DREB (dehydration-responsive element-binding) transcription factors play important roles in plant stress response and have been identified in a wide variety of plants. Studies on DREB are focused on the A-1 (DREB1) and A-2 (DREB2) groups. Studies on A-5 group DREBs, which represent a large proportion of the DREB subfamily, is limited. In this study, we characterized and analyzed the stress tolerance function of ScDREB10, an A-5c type DREB gene from the desert moss Syntrichia caninervis. Transactivation assay in yeast showed that ScDREB10 had transactivation activity. Transient expression assay revealed that ScDREB10 was distributed both in the nucleus and cytosol of tobacco leaf epidermal cells. Overexpression of ScDREB10 significantly increased the germination percentage of Arabidopsis seeds under osmotic and salt stresses, and improved the osmotic and salt stress tolerances of Arabidopsis at the seedling stage and is associated with the expression of downstream stress-related genes and improved reactive oxygen species (ROS) scavenging ability. Our study provides insight into the molecular mechanism of stress tolerance of A-5 type DREB proteins, as well as providing a promising candidate gene for crop salt and drought stress breeding.

In the difficult economic climate currently facing businesses of all sizes, focusing on marketing efforts that retain customers and build strong, profitable relationships has become more important than ever. This research, commissioned by database marketing and customer insight company GI insight, surveyed a cross-section of 1,000 UK customers on how well they felt the organisations they regularly deal with know them. The results, used to compile the 2013 Customer Intimacy Index, reveal which sectors are succeeding in winning over consumers and which are failing to do so. The findings highlight that while some sectors are effectively building strong relationships with customers by utilising their data to create personalised content and offers that earn customer loyalty, others are not doing a good enough job of building meaningful relationships with customers.

We report highly convenient Pd catalysts for the aerobic oxidation of alcohols, which are generated in situ by combining commercially available catalyst precursors. Systematic optimizations of the L- and X-type ligand environment and the employed additive allow the use of air as the sole oxidant without formation of Pd black. The resulting novel protocol provides quantitative yields of a broad variety of ketones and aldehydes.

Correction to Martin et al. available at: Genes & Development 30 (19): 2158 (http://genesdev.cshlp.org/content/31/9/953.full.pdf+html). Compaction of chromosomes is essential for accurate segregation of the genome duringmitosis. In vertebrates, two condensin complexes ensure timely chromosome condensation, sister chromatid disentanglement, and maintenance of mitotic chromosome structure. Here,we report that biallelic mutations inNCAPD2,NCAPH, orNCAPD3, encoding subunits of these complexes, cause microcephaly. In addition, hypomorphic Ncaph2 mice have significantly reduced brain size, with frequent anaphase chromatin bridge formation observed in apical neural progenitors during neurogenesis. Such DNA bridges also arise in condensin-deficient patient cells, where they are the consequence of failed sister chromatid disentanglement during chromosome compaction. This results in chromosome segregation errors, leading to micronucleus formation and increased aneuploidy in daughter cells. These findings establish “condensinopathies” as microcephalic disorders, with decatenation failure as an additional disease mechanism for microcephaly, implicating mitotic chromosome condensation as a key process ensuring mammalian cerebral cortex size. This work was supported by funding from the Medical Research Council, the Lister Institute for Preventative Medicine, and the European Research Council (ERC; 281847 to A.P.J.); a Biotechnology and Biological Sciences Research Council grant (BB/ K017632/1 to P.V); a Sir Henry Dale Fellowship (grant 102560/ Z/13/Z to A.J.W.); Medical Research Scotland (to L.S.B.); the Potentials Foundation (to C.A.W.); and the Indian Council of Medical Research (BMS 54/2/2013 to S.R.P). The Deciphering Developmental Disorders Study presents independent research commissioned by the Health Innovation Challenge Fund (grant no. HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant no. WT098051). The views expressed here are those of the authors and not necessarily those of the Wellcome Trust or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83) granted by the Cambridge South Research Ethics Committee, and GEN/ 284/12 granted by the Republic of Ireland. We acknowledge the support of the National Institute for Health Research through the Comprehensive Clinical Research Network.

Long noncoding RNAs (lncRNAs) have been implicated in various biological functions including regulation of gene expression, X-inactivation, imprinting, cell proliferation and differentiation. However, the functionality of lncRNAs is not clearly understood and conflicting conclusions have often been reached when comparing different methods to investigate them. Moreover, little is known about the upstream regulation of lncRNAs. Here we show that a transcriptional co activator – PC4 and SF2 interacting protein (Psip1)/p52, which is involved in linking transcription to RNA processing, regulates the expression of the lncRNA Hottip. Using complementary approaches – knockdown, Cas9 mediated lncRNA deletion, analysis of lncRNA binding by Chromatin isolation by RNA purification (ChIRP) - we demonstrate that Hottip binds to the 5’ Hoxa genes located in cis, which leads to their upregulation. Moreover, the synthetic activation of Hottip is sufficient to induce the expression ofpolycomb repressed Hox genes in mouse embryonic stem cells (mESCs).