bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brassica napusGLABRA3‐1 promotes anthocyanin biosynthesis and trichome formation in true leaves when expressed in Arabidopsis thaliana
Authors: Gao C. , Guo Y. , Wang J. , Li D. , Liu K. , Qi S. , Jin C. , Duan S. , Gong J. , Li Z. , Chen M. 
Published: September 2017

Abstract

Previous studies have shown that GLABRA3 (AtGL3), a bHLH transcription factor, plays essential roles in anthocyanin biosynthesis and trichome formation in Arabidopsis thaliana. However, there have been no such studies of a homologue, BnGL3, from the closely related crop, Brassica napus.

Here, we analysed the BnGL3‐1 coding domain sequence from the B. napus cultivar QINYOU Seven, identified conserved protein domains and performed a phylogenetic analysis to elucidate its relationship with homologues form a range of plant species. When expressed in tobacco leaves as a fusion protein with green fluorescent protein, BnGL3‐1 accumulated in the nucleus, consistent with its predicted function as a transcription factor.

Ectopic expression of the BnGL3‐1 gene in the A. thaliana gl3‐3 mutant resulted in levels of anthocyanins and numbers of trichomes in true leaves that were higher than in wild‐type plants. Moreover, overexpression of BnGL3‐1 in gl3‐3 compensated for the promotion and repression of genes involved in anthocyanin biosynthesis and trichome formation, respectively, that has been reported in gl3‐3 young shoots and expanding true leaves.

This study provides new insights into GL3 function in anthocyanin biosynthesis and trichome formation in crucifers, and represents a promising target for genetic manipulation of B. napus.
Boosting Factor-Specific Functional Historical Models for the Detection of Synchronization in Bioelectrical Signals
Authors: Rügamer David , Brockhaus Sarah , Gentsch Kornelia , Scherer Klaus , Greven Sonja 
Published: September 2017

SummaryThe link between different psychophysiological measures during emotion episodes is not well understood. To analyse the functional relationship between electroencephalography and facial electromyography, we apply historical function-on-function regression models to electroencephalography and electromyography data that were simultaneously recorded from 24 participants while they were playing a computerized gambling task. Given the complexity of the data structure for this application, we extend simple functional historical models to models including random historical effects, factor-specific historical effects and factor-specific random historical effects. Estimation is conducted by a componentwise gradient boosting algorithm, which scales well to large data sets and complex models.
Geometry, spatial arrangement and origin of carbonate grain‐dominated, scour‐fill and event‐bed deposits: Late Jurassic Jubaila Formation and Arab‐D Member, Saudi Arabia
Authors: Jacquemyn Carl , Jackson Matthew D. , Hampson Gary J. , John Cédric M. , Cantrell Dave L. , Zűhlke Rainer , AbuBshait AbdulJaleel , Lindsay Robert F. , Monsen Ronald 
Published: September 2017

AbstractOutcrop analogues of the Late Jurassic lower Arab‐D reservoir zone in Saudi Arabia expose a succession of fining‐upward cycles deposited on a distal middle‐ramp to outer‐ramp setting. These cycles are interrupted by erosional scours that incise up to 1·8 m into underlying deposits and are infilled with intraclasts up to boulder size (1 m diameter). Scours of similar size and infill are not commonly observed on low‐angle carbonate ramps. Outcrops have been used to characterize and quantify facies‐body geometries and spatial relationships. The coarse grain size of scour‐fills indicates scouring and boulder transport by debris or hyperconcentrated density flows strengthened by offshore‐directed currents. Longitudinal and lateral flow transformation is invoked to produce the ‘pit and wing’ geometry of the scours. Scour pits and wings erode up to 1·8 m and 0·7 m deep, respectively, and are on average 50 m wide between wing tips. The flat bases of the scours and their lack of consistent aspect ratio indicate that erosion depth was limited by the presence of cemented firmgrounds in underlying cycles. Scours define slightly sinuous channels that are consistently oriented north–south, sub‐parallel to the inferred regional depositional strike of the ramp, suggesting that local palaeobathymetry was more complex than commonly assumed. Weak lateral clustering of some scours indicates that they were underfilled and reoccupied by later scour incision and infill. Rudstone scour‐fills required reworking of material from inner ramp by high‐energy, offshore‐directed flows, associated with storm action and the hydraulic gradient produced by coastal storm setup, to generate erosion and sustain transport of clasts that are generally associated with steeper slopes. Quantitative analysis indicates that these coarse‐grained units have limited potential for correlation between wells as laterally continuous, highly permeable reservoir flow units, but their erosional and locally clustered character may increase effective vertical permeability of the Arab‐D reservoir zone as a whole.
Rural/Urban Disparities in Adolescent Nonfatal Suicidal Ideation and Suicide Attempt: A Population‐Based Study
Authors: Goldman‐Mellor Sidra , Allen Kristina , Kaplan Mark S. 
Published: September 2017

Adolescent suicide rates exhibit stark geographic disparities, with rates highest in rural areas. The causes of this disparity remain unclear. We investigated whether adolescent nonfatal suicidal ideation and attempt—leading risk factors for suicide—demonstrate the same rural/urban disparity. Using adolescent data from the 2011–2014 waves of the population‐representative California Health Interview Survey (CHIS; N = 4,616), we estimated associations between residence in a rural area and suicidal ideation and suicide attempt, as well as access to psychological care. Survey‐weighted logistic regression models controlled for individual‐ and family‐level covariates. Results showed that rural adolescents were, compared to urban adolescents, substantially less likely to report recent suicidal ideation (OR = 0.25, 95% confidence interval [CI] = 0.10, 0.61) and suicide attempt (OR = 0.17, 95% CI = 0.05, 0.66). Suicidal youths in rural and urban areas were equally likely, however, to report receiving psychological care. In this study, rural adolescents in California reported lower rates of nonfatal suicidal behavior compared to urban peers. This pattern contrasts with rates of adolescent suicide fatality, which are higher in rural areas. Results suggest that reducing geographic disparities in youth suicide may require multifaceted public health approaches, in addition to better identification and treatment for high‐risk adolescents.
Successful kidney transplantation in a patient with congenital thrombotic thrombocytopenic purpura (Upshaw‐Schulman syndrome)
Authors: Fattah Hasan , Kumar Dhiren , George James N. , Massey H. Davis , King Anne L. , Friedman Kenneth D. , Gupta Gaurav 
Published: September 2017

BACKGROUNDCongenital thrombotic thrombocytopenic purpura (TTP) may not be recognized until organ failure related to the microvascular thrombosis occurs. Kidney failure may be the initial presenting clinical feature. Kidney transplantation has been contraindicated because of the assumption that the continuing microvascular thrombosis will cause inevitable graft failure.CASE REPORTWe report a 48‐year‐old nulliparous woman who presented with end‐stage kidney disease that was attributed to hypertension. Her past history included a thromboembolic stroke at age 32, for which she was placed on permanent anticoagulation. Immediately after living unrelated‐donor kidney transplant, she developed severe hemolysis and acute decline in urine output for which she received red blood cell and platelet transfusions and an infusion of eculizumab (1200 mg). She promptly responded and was discharged on her fifth postoperative day with a serum creatinine level of 1.0 mg/dL. Two weeks later, thrombocytopenia and hemolysis recurred. By this time, undetectable ADAMTS13 activity (<5%) with no demonstrable inhibitor had been reported. She responded rapidly to plasma infusions. Genetic analysis confirmed the diagnosis of congenital TTP, documenting known pathogenic mutations in each of the ADAMTS13 genes. She continued to receive twice‐monthly infusions for 4 months. Surveillance kidney biopsies at 6 and 12 months posttransplant demonstrated no evidence of thrombotic microangiopathy or graft rejection. After 2 years of follow‐up her creatinine remains stable at 1.0 mg/dL (estimated glomerular filtration rate, 65 mL/min/1.73 m2).CONCLUSIONOur experience suggests that kidney transplantation may be an appropriate management for carefully selected patients with congenital TTP who develop end‐stage renal disease.
Molecular Evolution of Herpes Simplex Virus 2 Complete Genomes: Comparison between Primary and Recurrent Infections
Authors: Minaya Miguel A. , Jensen Travis L. , Goll Johannes B. , Korom Maria , Datla Sree H. , Belshe Robert B. , Morrison Lynda A. 
Published: September 2017

ABSTRACT
Herpes simplex virus 1 (HSV-1) and HSV-2 are large, double-stranded DNA viruses that cause lifelong persistent infections characterized by periods of quiescence and recurrent disease. How HSV evolves within an infected individual experiencing multiple episodes of recurrent disease over time is not known. We determined the genome sequences of viruses isolated from two subjects in the Herpevac Trial for Women who experienced primary HSV-2 genital disease and compared them with sequences of viruses isolated from the subsequent fifth or sixth episode of recurrent disease in the same individuals. Each of the HSV-2 genome sequences was initially obtained using next-generation sequencing and completed with Sanger sequencing. Polymorphisms over the entire genomes were mapped, and amino acid variants resulting from nonsynonymous changes were analyzed based on the secondary and tertiary structures of a previously crystallized protein. A phylogenetic reconstruction was used to assess relationships among the four HSV-2 samples, other North American sequences, and reference sequences. Little genetic drift was detected in viruses shed by the same subjects following repeated reactivation events, suggesting strong selective pressure on the viral genome to maintain sequence fidelity during reactivations from its latent state within an individual host. Our results also demonstrate that some primary HSV-2 isolates from North America more closely resemble the HG52 laboratory strain from Scotland than the low-passage-number clinical isolate SD90e from South Africa or laboratory strain 333. Thus, one of the sequences reported here would be a logical choice as a reference strain for inclusion in future studies of North American HSV-2 isolates.

IMPORTANCE
The extent to which the HSV-2 genome evolves during multiple episodes of reactivation from its latent state within an infected individual is not known. We used next-generation sequencing techniques to determine whole-genome sequences of four viral samples from two subjects in the Herpevac Trial. The sequence of each subject's well-documented primary isolate was compared with the sequence of the isolate from their fifth or sixth episode of recurrent disease. Only 19 genetic polymorphisms unique to the primary or recurrent isolate were identified, 10 in subject A and 9 in subject B. These observations indicate remarkable genetic conservation between primary and recurrent episodes of HSV-2 infection and imply that strong selection pressures exist to maintain the fidelity of the viral genome during repeated reactivations from its latent state. The genome conservation observed also has implications for the potential success of a therapeutic vaccine.
Susceptibility of Human Endogenous Retrovirus Type K to Reverse Transcriptase Inhibitors
Authors: Contreras-Galindo Rafael , Dube Derek , Fujinaga Koh , Kaplan Mark H. , Markovitz David M. 
Published: September 2017

ABSTRACTHuman endogenous retroviruses (HERVs) make up 8% of the human genome. The HERV type K (HERV-K) HML-2 (HK2) family contains proviruses that are the most recent entrants into the human germ line and are transcriptionally active. In HIV-1 infection and cancer, HK2 genes produce retroviral particles that appear to be infectious, yet the replication capacity of these viruses and potential pathogenicity has been difficult to ascertain. In this report, we screened the efficacy of commercially available reverse transcriptase inhibitors (RTIs) at inhibiting the enzymatic activity of HK2 RT and HK2 genomic replication. Interestingly, only one provirus, K103, was found to encode a functional RT among those examined. Several nucleoside analogue RTIs (NRTIs) blocked K103 RT activity and consistently inhibited the replication of HK2 genomes. The NRTIs zidovudine (AZT), stavudine (d4T), didanosine (ddI), and lamivudine (3TC), and the nucleotide RTI inhibitor tenofovir (TDF), show efficacy in blocking K103 RT. HIV-1-specific nonnucleoside RTIs (NNRTIs), protease inhibitors (PIs), and integrase inhibitors (IIs) did not affect HK2, except for the NNRTI etravirine (ETV). The inhibition of HK2 infectivity by NRTIs appears to take place at either the reverse transcription step of the viral genome prior to HK2 viral particle formation and/or in the infected cells. Inhibition of HK2 by these drugs will be useful in suppressing HK2 infectivity if these viruses prove to be pathogenic in cancer, neurological disorders, or other diseases associated with HK2. The present studies also elucidate a key aspect of the life cycle of HK2, specifically addressing how they do, and/or did, replicate.IMPORTANCEEndogenous retroviruses are relics of ancestral virus infections in the human genome. The most recent of these infections was caused by HK2. While HK2 often remains silent in the genome, this group of viruses is activated in HIV-1-infected and cancer cells. Recent evidence suggests that these viruses are infectious, and the potential exists for HK2 to contribute to disease. We show that HK2, and specifically the enzyme that mediates virus replication, can be inhibited by a panel of drugs that are commercially available. We show that several drugs block HK2 with different efficacies. The inhibition of HK2 replication by antiretroviral drugs appears to occur in the virus itself as well as after infection of cells. Therefore, these drugs might prove to be an effective treatment by suppressing HK2 infectivity in diseases where these viruses have been implicated, such as cancer and neurological syndromes.
p21 Restricts HIV-1 in Monocyte-Derived Dendritic Cells through the Reduction of Deoxynucleoside Triphosphate Biosynthesis and Regulation of SAMHD1 Antiviral Activity
Authors: Valle-Casuso Jose Carlos , Allouch Awatef , David Annie , Lenzi Gina M. , Studdard Lydia , Barré-Sinoussi Françoise , Müller-Trutwin Michaela , Kim Baek , Pancino Gianfranco , Sáez-Cirión Asier 
Published: September 2017

ABSTRACT
HIV-1 infection of noncycling cells, such as dendritic cells (DCs), is impaired due to limited availability of deoxynucleoside triphosphates (dNTPs), which are needed for HIV-1 reverse transcription. The levels of dNTPs are tightly regulated during the cell cycle and depend on the balance between dNTP biosynthesis and degradation. SAMHD1 potently blocks HIV-1 replication in DCs, although the underlying mechanism is still unclear. SAMHD1 has been reported to be able to degrade dNTPs and viral nucleic acids, which may both hamper HIV-1 reverse transcription. The relative contribution of these activities may differ in cycling and noncycling cells. Here, we show that inhibition of HIV-1 replication in monocyte-derived DCs (MDDCs) is associated with an increased expression of p21cip1/waf, a cell cycle regulator that is involved in the differentiation and maturation of DCs. Induction of p21 in MDDCs decreases the pool of dNTPs and increases the antiviral active isoform of SAMHD1. Although both processes are complementary in inhibiting HIV-1 replication, the antiviral activity of SAMHD1 in our primary cell model appears to be, at least partially, independent of its dNTPase activity. The reduction in the pool of dNTPs in MDDCs appears rather mostly due to a p21-mediated suppression of several enzymes involved in dNTP synthesis (i.e., RNR2, TYMS, and TK-1). These results are important to better understand the interplay between HIV-1 and DCs and may inform the design of new therapeutic approaches to decrease viral dissemination and improve immune responses against HIV-1.

IMPORTANCE
DCs play a key role in the induction of immune responses against HIV. However, HIV has evolved ways to exploit these cells, facilitating immune evasion and virus dissemination. We have found that the expression of p21, a cyclin-dependent kinase inhibitor involved in cell cycle regulation and monocyte differentiation and maturation, potentially can contribute to the inhibition of HIV-1 replication in monocyte-derived DCs through multiple mechanisms. p21 decreased the size of the intracellular dNTP pool. In parallel, p21 prevented SAMHD1 phosphorylation and promoted SAMHD1 dNTPase-independent antiviral activity. Thus, induction of p21 resulted in conditions that allowed the effective inhibition of HIV-1 replication through complementary mechanisms. Overall, p21 appears to be a key regulator of HIV infection in myeloid cells.
A DNA Vaccine That Targets Hemagglutinin to Antigen-Presenting Cells Protects Mice against H7 Influenza
Authors: Andersen Tor Kristian , Zhou Fan , Cox Rebecca , Bogen Bjarne , Grødeland Gunnveig 
Published: September 2017

ABSTRACTZoonotic influenza H7 viral infections have a case fatality rate of about 40%. Currently, no or limited human to human spread has occurred, but we may be facing a severe pandemic threat if the virus acquires the ability to transmit between humans. Novel vaccines that can be rapidly produced for global distribution are urgently needed, and DNA vaccines may be the only type of vaccine that allows for the speed necessary to quench an emerging pandemic. Here, we constructed DNA vaccines encoding the hemagglutinin (HA) from influenza A/chicken/Italy/13474/99 (H7N1). In order to increase the efficacy of DNA vaccination, HA was targeted to either major histocompatibility complex class II molecules or chemokine receptors 1, 3, and 5 (CCR1/3/5) that are expressed on antigen-presenting cells (APC). A single DNA vaccination with APC-targeted HA significantly increased antibody levels in sera compared to nontargeted control vaccines. The antibodies were confirmed neutralizing in an H7 pseudotype-based neutralization assay. Furthermore, the APC-targeted vaccines increased the levels of antigen-specific cytotoxic T cells, and a single DNA vaccination could confer protection against a lethal challenge with influenza A/turkey/Italy/3889/1999 (H7N1) in mice. In conclusion, we have developed a vaccine that rapidly could contribute protection against a pandemic threat from avian influenza.IMPORTANCEHighly pathogenic avian influenza H7 constitute a pandemic threat that can cause severe illness and death in infected individuals. Vaccination is the main method of prophylaxis against influenza, but current vaccine strategies fall short in a pandemic situation due to a prolonged production time and insufficient production capabilities. In contrast, a DNA vaccine can be rapidly produced and deployed to prevent the potential escalation of a highly pathogenic influenza pandemic. We here demonstrate that a single DNA delivery of hemagglutinin from an H7 influenza could mediate full protection against a lethal challenge with H7N1 influenza in mice. Vaccine efficacy was contingent on targeting of the secreted vaccine protein to antigen-presenting cells.
Zika Virus Encoding Nonglycosylated Envelope Protein Is Attenuated and Defective in Neuroinvasion
Authors: Annamalai Arun S. , Pattnaik Aryamav , Sahoo Bikash R. , Muthukrishnan Ezhumalai , Natarajan Sathish Kumar , Steffen David , Vu Hiep L. X. , Delhon Gustavo , Osorio Fernando A. , Petro Thomas M. , Xiang Shi-Hua , Pattnaik Asit K. 
Published: September 2017

ABSTRACT
Zika virus (ZIKV), a mosquito-transmitted flavivirus responsible for sporadic outbreaks of mild and febrile illness in Africa and Asia, reemerged in the last decade causing serious human diseases, including microcephaly, congenital malformations, and Guillain-Barré syndrome. Although genomic and phylogenetic analyses suggest that genetic evolution may have led to the enhanced virulence of ZIKV, experimental evidence supporting the role of specific genetic changes in virulence is currently lacking. One sequence motif, VNDT, containing an N-linked glycosylation site in the envelope (E) protein, is polymorphic; it is absent in many of the African isolates but present in all isolates from the recent outbreaks. In the present study, we investigated the roles of this sequence motif and glycosylation of the E protein in the pathogenicity of ZIKV. We first constructed a stable full-length cDNA clone of ZIKV in a novel linear vector from which infectious virus was recovered. The recombinant ZIKV generated from the infectious clone, which contains the VNDT motif, is highly pathogenic and causes lethality in a mouse model. In contrast, recombinant viruses from which the VNDT motif is deleted or in which the N-linked glycosylation site is mutated by single-amino-acid substitution are highly attenuated and nonlethal. The mutant viruses replicate poorly in the brains of infected mice when inoculated subcutaneously but replicate well following intracranial inoculation. Our findings provide the first evidence that N-linked glycosylation of the E protein is an important determinant of ZIKV virulence and neuroinvasion.

IMPORTANCE
The recent emergence of Zika virus (ZIKV) in the Americas has caused major worldwide public health concern. The virus appears to have gained significant pathogenicity, causing serious human diseases, including microcephaly and Guillain-Barré syndrome. The factors responsible for the emergence of pathogenic ZIKV are not understood at this time, although genetic changes have been shown to facilitate virus transmission. All isolates from the recent outbreaks contain an N-linked glycosylation site within the viral envelope (E) protein, whereas many isolates of the African lineage virus lack this site. To elucidate the functional significance of glycosylation in ZIKV pathogenicity, recombinant ZIKVs from infectious clones with or without the glycan on the E protein were generated. ZIKVs lacking the glycan were highly attenuated for the ability to cause mortality in a mouse model and were severely compromised for neuroinvasion. Our studies suggest glycosylation of the E protein is an important factor contributing to ZIKV pathogenicity.