bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural insights of non-canonical U•U pair and Hoogsteen interaction probed with Se atom
Authors: Sheng Jia , Gan Jianhua , Soares Alexei S. , Salon Jozef , Huang Zhen 
Published: September 2013

Abstract
Unlike DNA, in addition to the 2′-OH group, uracil nucleobase and its modifications play essential roles in structure and function diversities of non-coding RNAs. Non-canonical U•U base pair is ubiquitous in non-coding RNAs, which are highly diversified. However, it is not completely clear how uracil plays the diversifing roles. To investigate and compare the uracil in U-A and U•U base pairs, we have decided to probe them with a selenium atom by synthesizing the novel 4-Se-uridine (SeU) phosphoramidite and Se-nucleobase-modified RNAs (SeU-RNAs), where the exo-4-oxygen of uracil is replaced by selenium. Our crystal structure studies of U-A and U•U pairs reveal that the native and Se-derivatized structures are virtually identical, and both U-A and U•U pairs can accommodate large Se atoms. Our thermostability and crystal structure studies indicate that the weakened H-bonding in U-A pair may be compensated by the base stacking, and that the stacking of the trans-Hoogsteen U•U pairs may stabilize RNA duplex and its junction. Our result confirms that the hydrogen bond (O4…H-C5) of the Hoogsteen pair is weak. Using the Se atom probe, our Se-functionalization studies reveal more insights into the U•U interaction and U-participation in structure and function diversification of nucleic acids.
Co-operation of BRCA1 and POH1 relieves the barriers posed by 53BP1 and RAP80 to resection
Authors: Kakarougkas Andreas , Ismail Amani , Katsuki Yoko , Freire Raimundo , Shibata Atsushi , Jeggo Penny A. 
Published: September 2013

Abstract
In G2 phase cells, DNA double-strand break repair switches from DNA non-homologous end-joining to homologous recombination. This switch demands the promotion of resection. We examine the changes in 53BP1 and RAP80 ionizing radiation induced foci (IRIF) in G2 phase, as these are factors that restrict resection. We observed a 2-fold increase in the volume of 53BP1 foci by 8 h, which is not seen in G1 cells. Additionally, an IRIF core devoid of 53BP1 arises where RPA foci form, with BRCA1 IRIF forming between 53BP1 and replication protein A (RPA). Ubiquitin chains assessed using α-FK2 antibodies are similarly repositioned. Repositioning of all these components requires BRCA1’s BRCT but not the ring finger domain. 53BP1, RAP80 and ubiquitin chains are enlarged following POH1 depletion by small interfering RNA, but a devoid core does not form and RPA foci formation is impaired. Co-depletion of POH1 and RAP80, BRCC36 or ABRAXAS allows establishment of the 53BP1 and ubiquitin chain-devoid core. Thus, the barriers posed by 53BP1 and RAP80 are relieved by BRCA1 and POH1, respectively. Analysis of combined depletions shows that these represent distinct but interfacing barriers to promote loss of ubiquitin chains in the IRIF core, which is required for subsequent resection. We propose a model whereby BRCA1 impacts on 53BP1 to allow access of POH1 to RAP80. POH1-dependent removal of RAP80 within the IRIF core enables degradation of ubiquitin chains, which promotes loss of 53BP1. Thus, POH1 represents a novel component regulating the switch from non-homologous end-joining to homologous recombination.
Suppression of HPV-16 late L1 5′-splice site SD3632 by binding of hnRNP D proteins and hnRNP A2/B1 to upstream AUAGUA RNA motifs
Authors: Li Xiaoze , Johansson Cecilia , Glahder Jacob , Mossberg Ann-Kristin , Schwartz Stefan 
Published: September 2013

Abstract
Human papillomavirus type 16 (HPV-16) 5′-splice site SD3632 is used exclusively to produce late L1 mRNAs. We identified a 34-nt splicing inhibitory element located immediately upstream of HPV-16 late 5′-splice site SD3632. Two AUAGUA motifs located in these 34 nt inhibited SD3632. Two nucleotide substitutions in each of the HPV-16 specific AUAGUA motifs alleviated splicing inhibition and induced late L1 mRNA production from episomal forms of the HPV-16 genome in primary human keratinocytes. The AUAGUA motifs bind specifically not only to the heterogeneous nuclear RNP (hnRNP) D family of RNA-binding proteins including hnRNP D/AUF, hnRNP DL and hnRNP AB but also to hnRNP A2/B1. Knock-down of these proteins induced HPV-16 late L1 mRNA expression, and overexpression of hnRNP A2/B1, hnRNP AB, hnRNP DL and the two hnRNP D isoforms hnRNP D37 and hnRNP D40 further suppressed L1 mRNA expression. This inhibition may allow HPV-16 to hide from the immune system and establish long-term persistent infections with enhanced risk at progressing to cancer. There is an inverse correlation between expression of hnRNP D proteins and hnRNP A2/B1 and HPV-16 L1 production in the cervical epithelium, as well as in cervical cancer, supporting the conclusion that hnRNP D proteins and A2/B1 inhibit HPV-16 L1 mRNA production.
Reconfiguration of Network Hub Structure after Propofol-induced Unconsciousness
Authors: Lee Heonsoo , Mashour George A. , Noh Gyu-Jeong , Kim Seunghwan , Lee UnCheol 
Published: September 2013

Abstract

Introduction:
General anesthesia induces unconsciousness along with functional changes in brain networks. Considering the essential role of hub structures for efficient information transmission, the authors hypothesized that anesthetics have an effect on the hub structure of functional brain networks.

Methods:
Graph theoretical network analysis was carried out to study the network properties of 21-channel electroencephalogram data from 10 human volunteers anesthetized on two occasions. The functional brain network was defined by Phase Lag Index, a coherence measure, for three states: wakefulness, loss of consciousness induced by the anesthetic propofol, and recovery of consciousness. The hub nodes were determined by the largest centralities. The correlation between the altered hub organization and the phase relationship between electroencephalographic channels was investigated.

Results:
Topology rather than connection strength of functional networks correlated with states of consciousness. The average path length, clustering coefficient, and modularity significantly increased after administration of propofol, which disrupted long-range connections. In particular, the strength of hub nodes significantly decreased. The primary hub location shifted from the parietal to frontal region, in association with propofol-induced unconsciousness. The phase lead of frontal to parietal regions in the α frequency band (8–13 Hz) observed during wakefulness reversed direction after propofol and returned during recovery.

Conclusions:
Propofol reconfigures network hub structure in the brain and reverses the phase relationship between frontal and parietal regions. Changes in network topology are more closely associated with states of consciousness than connectivity and may be the primary mechanism for the observed loss of frontal to parietal feedback during general anesthesia.
Alterations in Seed Development Gene Expression Affect Size and Oil Content of Arabidopsis Seeds
Authors: Fatihi Abdelhak , Zbierzak Anna Maria , Dörmann Peter 
Published: September 2013

Abstract
Seed endosperm development in Arabidopsis (Arabidopsis thaliana) is under control of the polycomb group complex, which includes Fertilization Independent Endosperm (FIE). The polycomb group complex regulates downstream factors, e.g. Pheres1 (PHE1), by genomic imprinting. In heterozygous fie mutants, an endosperm develops in ovules carrying a maternal fie allele without fertilization, finally leading to abortion. Another endosperm development pathway depends on MINISEED3 (a WRKY10 transcription factor) and HAIKU2 (a leucine-rich repeat kinase). While the role of seed development genes in the embryo and endosperm establishment has been studied in detail, their impact on metabolism and oil accumulation remained unclear. Analysis of oil, protein, and sucrose accumulation in mutants and overexpression plants of the four seed development genes revealed that (1) seeds carrying a maternal fie allele accumulate low oil with an altered composition of triacylglycerol molecular species; (2) homozygous mutant seeds of phe1, mini3, and iku2, which are smaller, accumulate less oil and slightly less protein, and starch, which accumulates early during seed development, remains elevated in mutant seeds; (3) embryo-specific overexpression of FIE, PHE1, and MINI3 has no influence on seed size and weight, nor on oil, protein, or sucrose content; and (4) overexpression of IKU2 results in seeds with increased size and weight, and oil content of overexpressed IKU2 seeds is increased by 35%. Thus, IKU2 overexpression represents a novel strategy for the genetic manipulation of the oil content in seeds.
Tissue-Specific Profiling Reveals Transcriptome Alterations inArabidopsisMutants Lacking Morphological Phenotypes
Authors: Simon Marissa , Bruex Angela , Kainkaryam Raghunandan M. , Zheng Xiaohua , Huang Ling , Woolf Peter J. , Schiefelbein John 
Published: September 2013

AbstractTraditional genetic analysis relies on mutants with observable phenotypes. Mutants lacking visible abnormalities may nevertheless exhibit molecular differences useful for defining gene function. To examine this, we analyzed tissue-specific transcript profiles from Arabidopsis thaliana transcription factor gene mutants with known roles in root epidermis development, but lacking a single-gene mutant phenotype due to genetic redundancy. We discovered substantial transcriptional changes in each mutant, preferentially affecting root epidermal genes in a manner consistent with the known double mutant effects. Furthermore, comparing transcript profiles of single and double mutants, we observed remarkable variation in the sensitivity of target genes to the loss of one or both paralogous genes, including preferential effects on specific branches of the epidermal gene network, likely reflecting the pathways of paralog subfunctionalization during evolution. In addition, we analyzed the root epidermal transcriptome of the transparent testa glabra2 mutant to clarify its role in the network. These findings provide insight into the molecular basis of genetic redundancy and duplicate gene diversification at the level of a specific gene regulatory network, and they demonstrate the usefulness of tissue-specific transcript profiling to define gene function in mutants lacking informative visible changes in phenotype.
COPPER RESPONSE REGULATOR1–Dependent and –Independent Responses of theChlamydomonas reinhardtiiTranscriptome to Dark Anoxia
Authors: Hemschemeier Anja , Casero David , Liu Bensheng , Benning Christoph , Pellegrini Matteo , Happe Thomas , Merchant Sabeeha S. 
Published: September 2013

AbstractAnaerobiosis is a stress condition for aerobic organisms and requires extensive acclimation responses. We used RNA-Seq for a whole-genome view of the acclimation of Chlamydomonas reinhardtii to anoxic conditions imposed simultaneously with transfer to the dark. Nearly 1.4 × 103 genes were affected by hypoxia. Comparing transcript profiles from early (hypoxic) with those from late (anoxic) time points indicated that cells activate oxidative energy generation pathways before employing fermentation. Probable substrates include amino acids and fatty acids (FAs). Lipid profiling of the C. reinhardtii cells revealed that they degraded FAs but also accumulated triacylglycerols (TAGs). In contrast with N-deprived cells, the TAGs in hypoxic cells were enriched in desaturated FAs, suggesting a distinct pathway for TAG accumulation. To distinguish transcriptional responses dependent on COPPER RESPONSE REGULATOR1 (CRR1), which is also involved in hypoxic gene regulation, we compared the transcriptomes of crr1 mutants and complemented strains. In crr1 mutants, ∼40 genes were aberrantly regulated, reaffirming the importance of CRR1 for the hypoxic response, but indicating also the contribution of additional signaling strategies to account for the remaining differentially regulated transcripts. Based on transcript patterns and previous results, we conclude that nitric oxide–dependent signaling cascades operate in anoxic C. reinhardtii cells.
Activation of nuclear factor erythroid 2‐related factor 2 (Nrf2) and Nrf‐2‐dependent genes by ischaemic pre‐conditioning and post‐conditioning: new adaptive endogenous protective responses against renal ischaemia/reperfusion injury
Authors: Shokeir A. A. , Hussein A. M. , Barakat N. , Abdelaziz A. , Elgarba M. , Awadalla A. 
Published: September 2013

AbstractAimTo investigate the impact of ischaemic pre‐conditioning (Ipre) and post‐conditioning (Ipost) on expression of nuclear factor erythroid 2‐related factor 2 (Nrf2) gene and its dependent genes, haem oxygenase‐1 (HO‐1) and NADPH‐quinone oxidoreductase‐1 (NQO‐1); inflammatory cytokines TNF‐α, IL1β and ICAM‐1; and apoptotic markers such as caspase‐3 in renal ischaemia/reperfusion (I/R) injury.MethodsOne hundred and fifty male Sprague Dawley rats were classified into five groups (each consisted of 30 rats): sham, control (I/R), Ipre + I/R, Ipre without I/R and Ipost + I/R. Serum creatinine and blood urea nitrogen (BUN) were measured at 2, 24 and 48 h after ischaemia. In kidney tissues, mRNA of Nrf2, HO‐1, NQO‐1, TNF‐α, IL‐1β and ICAM‐1 and immunohistochemical expression of Nrf2 and caspase‐3 were assessed.ResultsSerum creatinine and BUN improved significantly in Pre + I/R group; however, they did not show any significant improvement in Post + I/R group. Also, Ipre‐I/R group showed non‐significant change in serum creatinine and BUN. The expression of Nrf2, HO‐1 and NQO‐1 is increased significantly in Pre + I/R and Pre − I/R groups, while the enhancement in Post + I/R group was non‐significant. Moreover, the expression of proinflammatory cytokines (TNF‐α, IL‐1 and ICAM‐1) and apoptotic (caspase‐3) markers showed high significant attenuation in Pre + I/R group, but slight significant attenuation in Pre + I/R group.ConclusionThe renoprotective action of Ipre might include early activation and enhanced expression of Nrf2 gene and its dependent antioxidant genes, HO‐1 and NOQ1, as endogenous adaptive renoprotective genes, as well as reduction in TNF‐α, IL‐1β, ICAM‐1 and caspase‐3.
Attachment: Developmental pathways to affective dysregulation in young people at ultra‐high risk of developing psychosis
Authors: Gajwani Ruchika , Patterson Paul , Birchwood Max 
Published: September 2013

ObjectiveEmbedded in attachment theory is its association with affect regulation, which provides a framework for affective dysregulation in the emerging psychosis.MethodFifty‐one participants meeting criteria for ultra‐high risk (UHR) of developing psychosis were recruited from a youth mental health service within the United Kingdom. At intake baseline, prior to starting therapeutic intervention, all clients were assessed on measures of affective dysregulation and attachment.ResultsA large proportion of our sample (N = 51) reported clinically significant levels of depression (78%), state anxiety (59%), and social anxiety (65%). Eighty per cent of the UHR sample was insecurely attached. Insecure attachment was significantly associated with elevated depression and social anxiety. Attachment styles were associated with anxiety, depression, and social anxiety. There was no support for a mediating role of social anxiety between attachment styles and depression.ConclusionClinically significant levels of distress and anxiety experienced by the young people at high risk of psychosis. Clinical implications for the treatment of affective dysregulation in young people at UHR in relation to their attachment styles have been discussed.Practitioner points

The treatment of affective dysregulation has implications on social integration, crucial to the recovery of young people in the emerging psychosis.

Assessment of adult attachment difficulties may bring to the forefront specific negative internal working models (and interpersonal schemas) which may indicate vulnerability to social anxiety and depression.

Young adults at ultra‐high risk of psychosis with emotional difficulties may be better at help seeking and therefore over‐represented in this sample.

Cross‐sectional data analysis makes it difficult to draw aetiological links between adult attachment and affective dysregulation.
Overexpression of nuclear distribution protein (hNUDC) causes pro‐apoptosis and differentiation in Dami megakaryocytes
Authors: Xiao Y. , Zheng Y. , Tan P. , Xu P. , Zhang Q. 
Published: September 2013

AbstractObjectivesOverexpression of hNUDC, a member of the nuclear distribution protein family, reduces cell population growth in prostate cancer cell lines, concurrent with induced morphological change and enhanced polyploidization. These phenomena are also closely associated with terminal phases of megakaryocyte maturation.Materials and methodsIn Dami cells, MTT and trypan blue assays were used to investigate cell viability and proliferation effects of hNUDC, and flow cytometry was used to analyse cell cycle and DNA content. Real‐time RT‐PCR was employed to detect mRNA expression. Activations of caspase‐3, ERK, Akt and Stat‐5 were determined by immunoblotting. May‐Grünwald–Giemsa staining was performed to reveal cell morphology.Results and conclusionFunctional studies using adenovirus‐mediated hNUDC overexpression led to inhibition of megakaryocyte proliferation via cell cycle arrest in G2/M transition phase. This process could have been be mediated by upregulation of p21 and downregulation of its downstream targets, including cyclin B1, cyclin B2 and c‐myc. Enhanced apoptosis in turn ensued, characterized by increased caspase‐3 activation, upregulation of pro‐apoptotic Bax and downregulation of anti‐apoptotic Bcl‐2. Furthermore, hNUDC overexpression elevated the level of megakaryocyte maturation, associated with increased polyploidy, cell morphological changes and increased expression of cell surface differentiation markers, including CD10, CD44, CD41 and CD61. Our results further suggest that the ERK signalling pathway was involved in hNUDC overexpression‐induced apoptosis. Taken together, this study provides experimental evidence for overexpression of hNUDC in Dami cells and suggests that activation of apoptotic machinery may be involved in megakaryocytic differentiation.
Dual impacts of climate change: forest migration and turnover through life history
Authors: Zhu Kai , Woodall Christopher W. , Ghosh Souparno , Gelfand Alan E. , Clark James S. 
Published: September 2013

AbstractTree species are predicted to track future climate by shifting their geographic distributions, but climate‐mediated migrations are not apparent in a recent continental‐scale analysis. To better understand the mechanisms of a possible migration lag, we analyzed relative recruitment patterns by comparing juvenile and adult tree abundances in climate space. One would expect relative recruitment to be higher in cold and dry climates as a result of tree migration with juveniles located further poleward than adults. Alternatively, relative recruitment could be higher in warm and wet climates as a result of higher tree population turnover with increased temperature and precipitation. Using theUSDAForest Service's Forest Inventory and Analysis data at regional scales, we jointly modeled juvenile and adult abundance distributions for 65 tree species in climate space of the eastern United States. We directly compared the optimal climate conditions for juveniles and adults, identified the climates where each species has high relative recruitment, and synthesized relative recruitment patterns across species. Results suggest that for 77% and 83% of the tree species, juveniles have higher optimal temperature and optimal precipitation, respectively, than adults. Across species, the relative recruitment pattern is dominated by relatively more abundant juveniles than adults in warm and wet climates. These different abundance‐climate responses through life history are consistent with faster population turnover and inconsistent with the geographic trend of large‐scale tree migration. Taken together, this juvenile–adult analysis suggests that tree species might respond to climate change by having faster turnover as dynamics accelerate with longer growing seasons and higher temperatures, before there is evidence of poleward migration at biogeographic scales.
Corticomedullary differentiation and maturational arrest in thymomas
Authors: Ströbel Philipp , Hartmann Elena , Rosenwald Andreas , Kalla Jörg , Ott German , Friedel Godehard , Schalke Berthold , Kasahara Masanori , Tomaru Utano , Marx Alexander 
Published: September 2013

AimsMorphological complexity hampers the histological classification of thymomas. Our aim was to determine whether the use of novel differentiation and maturation markers of cortical and medullary thymic epithelial cells (cTECs and mTECs) might provide an approach to understanding the underlying biology of these tumours.Methods and resultsFifty‐seven thymomas were studied by immunohistochemistry. The cortical markers used were B5T, PRSS16, and cathepsin V. The medullary markers used were CD40, claudin‐4, AIRE, and desmin. Involucrin and cytokeratin 10 were used to study terminal mTEC maturation. Irrespective of histological subtype, most thymomas contained distinct areas with cortical and medullary differentiation. Type B1, type B2 and type AB thymomas showed marked bi‐lineage differentiation, with lack of terminal mTEC maturation in type AB. Type AB thymomas were unique in showing areas where cells with either cortical or medullary differentiation were intimately ‘mixed’ at the single‐cell level. Type B3 and type A thymomas showed only abortive lineage differentiation and maturation.ConclusionsThymomas show highly characteristic patterns of bi‐lineage TEC differentiation that reflect the histological subtypes recognized by the WHO classification. We hypothesize that thymomas arise from thymic precursor cells with different cortical and/or medullary maturation defects.
Four views of Riehl's melanosis: clinical appearance, dermoscopy, confocal microscopy and histopathology
Authors: Wang L. , Xu A.‐E. 
Published: September 2013

AbstractBackgroundRiehl's melanosis often poses a diagnostic challenge because of the variability in clinical morphology. Reflectance confocal microscopy (RCM), similar to dermoscopy, images lesions in an en face plane, thus enabling direct correlations with dermoscopic images. No published data are currently available regarding dermoscopic and RCM findings in Riehl's melanosis.ObjectivesThe aim of our study was to correlate the features of Riehl's melanosis across various imaging modalities including dermoscopy, confocal microscopy and histopathological examination to give a more precise description of this disease to improve the accuracy of diagnosis.MethodsFifteen patients with a previously established diagnosis of Riehl's melanosis were recruited. All lesions were imaged using dermoscope and in vivo RCM, followed by complete excision for histopathological analysis.ResultsA series of dermoscopic and RCM features of Riehl's melanosis were identified and shown to correlate well with histopathological examination. Pseudonetworks, grey dots/granules, liquefaction of basal cells, incontinence of pigment were the most distinctive characteristic.ConclusionsThis study highlights the clinical, dermoscopic, confocal microscopic and histopathological features of Riehl's melanosis. It is necessary to further define the diagnostic features of clinically difficult lesions with these modalities, but clinical evaluation should not be neglected.