bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electron Transfer to Nitrogenase in Different Genomic and Metabolic Backgrounds
Authors: Poudel Saroj , Colman Daniel R. , Fixen Kathryn R. , Ledbetter Rhesa N. , Zheng Yanning , Pence Natasha , Seefeldt Lance C. , Peters John W. , Harwood Caroline S. , Boyd Eric S. 
Published: February 2018

ABSTRACT

Nitrogenase catalyzes the reduction of dinitrogen (N
2
) using low-potential electrons from ferredoxin (Fd) or flavodoxin (Fld) through an ATP-dependent process. Since its emergence in an anaerobic chemoautotroph, this oxygen (O
2
)-sensitive enzyme complex has evolved to operate in a variety of genomic and metabolic backgrounds, including those of aerobes, anaerobes, chemotrophs, and phototrophs. However, whether pathways of electron delivery to nitrogenase are influenced by these different metabolic backgrounds is not well understood. Here, we report the distribution of homologs of Fds, Flds, and Fd-/Fld-reducing enzymes in 359 genomes of putative N
2
fixers (diazotrophs). Six distinct lineages of nitrogenase were identified, and their distributions largely corresponded to differences in the host cells' ability to integrate O
2
or light into energy metabolism. The predicted pathways of electron transfer to nitrogenase in aerobes, facultative anaerobes, and phototrophs varied from those in anaerobes at the levels of Fds/Flds used to reduce nitrogenase, the enzymes that generate reduced Fds/Flds, and the putative substrates of these enzymes. Proteins that putatively reduce Fd with hydrogen or pyruvate were enriched in anaerobes, while those that reduce Fd with NADH/NADPH were enriched in aerobes, facultative anaerobes, and anoxygenic phototrophs. The energy metabolism of aerobic, facultatively anaerobic, and anoxygenic phototrophic diazotrophs often yields reduced NADH/NADPH that is not sufficiently reduced to drive N
2
reduction. At least two mechanisms have been acquired by these taxa to overcome this limitation and to generate electrons with potentials capable of reducing Fd. These include the bifurcation of electrons or the coupling of Fd reduction to reverse ion translocation.

IMPORTANCE
Nitrogen fixation supplies fixed nitrogen to cells from a variety of genomic and metabolic backgrounds, including those of aerobes, facultative anaerobes, chemotrophs, and phototrophs. Here, using informatics approaches applied to genomic data, we show that pathways of electron transfer to nitrogenase in metabolically diverse diazotrophic taxa have diversified primarily in response to host cells' acquired ability to integrate O
2
or light into their energy metabolism. The acquisition of two key enzyme complexes enabled aerobic and facultatively anaerobic phototrophic taxa to generate electrons of sufficiently low potential to reduce nitrogenase: the bifurcation of electrons via the Fix complex or the coupling of Fd reduction to reverse ion translocation via the
Rhodobacter
nitrogen fixation (Rnf) complex.
Long Noncoding RNA uc002yug.2 Activates HIV-1 Latency through Regulation of mRNA Levels of Various RUNX1 Isoforms and Increased Tat Expression
Authors: Huan Chen , Li Zhaolong , Ning Shanshan , Wang Hong , Yu Xiao-Fang , Zhang Wenyan 
Published: February 2018

ABSTRACT

The HIV-1 reservoir is a major obstacle to complete eradication of the virus. Although many proteins and RNAs have been characterized as regulators in HIV-1/AIDS pathogenesis and latency, only a few long noncoding RNAs (lncRNAs) have been shown to be closely associated with HIV-1 replication and latency. In this study, we demonstrated that lncRNA uc002yug.2 plays a key role in HIV-1 replication and latency. uc002yug.2 potentially enhances HIV-1 replication, long terminal repeat (LTR) activity, and the activation of latent HIV-1 in both cell lines and CD4
+
T cells from patients. Further investigation revealed that uc002yug.2 activates latent HIV-1 through downregulating RUNX1b and -1c and upregulating Tat protein expression. The accumulated evidence supports our model that the Tat protein has the key role in the uc002yug.2-mediated regulatory effect on HIV-1 reactivation. Moreover, uc002yug.2 showed an ability to activate HIV-1 similar to that of suberoylanilide hydroxamic acid or phorbol 12-myristate 13-acetate using latently infected cell models. These findings improve our understanding of lncRNA regulation of HIV-1 replication and latency, providing new insights into potential targeted therapeutic interventions.

IMPORTANCE
The latent viral reservoir is the primary obstacle to curing HIV-1 disease. To date, only a few lncRNAs, which play major roles in various biological processes, including viral infection, have been identified as regulators in HIV-1 latency. In this study, we demonstrated that lncRNA uc002yug.2 is important for both HIV-1 replication and activation of latent viruses. Moreover, uc002yug.2 was shown to activate latent HIV-1 through regulating alternative splicing of RUNX1 and increasing the expression of Tat protein. These findings highlight the potential merit of targeting lncRNA uc002yug.2 as an activating agent for latent HIV-1.
Enhanced Human-Type Receptor Binding by Ferret-Transmissible H5N1 with a K193T Mutation
Authors: Peng Wenjie , Bouwman Kim M. , McBride Ryan , Grant Oliver C. , Woods Robert J. , Verheije Monique H. , Paulson James C. , de Vries Robert P. 
Published: February 2018

ABSTRACT
All human influenza pandemics have originated from avian influenza viruses. Although multiple changes are needed for an avian virus to be able to transmit between humans, binding to human-type receptors is essential. Several research groups have reported mutations in H5N1 viruses that exhibit specificity for human-type receptors and promote respiratory droplet transmission between ferrets. Upon detailed analysis, we have found that these mutants exhibit significant differences in fine receptor specificity compared to human H1N1 and H3N2 and retain avian-type receptor binding. We have recently shown that human influenza viruses preferentially bind to α2-6-sialylated branched N-linked glycans, where the sialic acids on each branch can bind to receptor sites on two protomers of the same hemagglutinin (HA) trimer. In this binding mode, the glycan projects over the 190 helix at the top of the receptor-binding pocket, which in H5N1 would create a stearic clash with lysine at position 193. Thus, we hypothesized that a K193T mutation would improve binding to branched N-linked receptors. Indeed, the addition of the K193T mutation to the H5 HA of a respiratory-droplet-transmissible virus dramatically improves both binding to human trachea epithelial cells and specificity for extended α2-6-sialylated N-linked glycans recognized by human influenza viruses.

IMPORTANCE
Infections by avian H5N1 viruses are associated with a high mortality rate in several species, including humans. Fortunately, H5N1 viruses do not transmit between humans because they do not bind to human-type receptors. In 2012, three seminal papers have shown how these viruses can be engineered to transmit between ferrets, the human model for influenza virus infection. Receptor binding, among others, was changed, and the viruses now bind to human-type receptors. Receptor specificity was still markedly different compared to that of human influenza viruses. Here we report an additional mutation in ferret-transmissible H5N1 that increases human-type receptor binding. K193T seems to be a common receptor specificity determinant, as it increases human-type receptor binding in multiple subtypes. The K193T mutation can now be used as a marker during surveillance of emerging viruses to assess potential pandemic risk.
Neurofilament light chain and tau concentrations are markedly increased in the serum of patients with sporadic Creutzfeldt-Jakob disease, and tau correlates with rate of disease progression
Authors: Thompson Andrew Geoffrey Bourne , Luk Connie , Heslegrave Amanda J , Zetterberg Henrik , Mead Simon H , Collinge John , Jackson Graham S 
Published: February 2018

ObjectivesA blood-based biomarker of neuronal damage in sporadic Creutzfeldt-Jakob disease (sCJD) will be extremely valuable for both clinical practice and research aiming to develop effective therapies.MethodsWe used an ultrasensitive immunoassay to measure two candidate biomarkers, tau and neurofilament light (NfL), in serum from patients with sCJD and healthy controls. We tested longitudinal sample sets from six patients to investigate changes over time, and examined correlations with rate of disease progression and associations with known phenotype modifiers.ResultsSerum concentrations of both tau and NfL were increased in patients with sCJD. NfL distinguished patients from controls with 100% sensitivity and 100% specificity. Tau did so with 91% sensitivity and 83% specificity. Both tau and NfL appeared to increase over time in individual patients, particularly in those with several samples tested late in their disease. Tau, but not NfL, was positively correlated with rate of disease progression, and was particularly increased in patients homozygous for methionine at codon 129 of PRNP.ConclusionsThese findings independently replicate other recent studies using similar methods and offer novel insights. They show clear promise for these blood-based biomarkers in prion disease. Future work should aim to fully establish their potential roles for monitoring disease progression and response to therapies.
Does HIV pre-exposure prophylaxis use lead to a higher incidence of sexually transmitted infections? A case-crossover study of men who have sex with men in Los Angeles, California
Authors: Beymer Matthew R , DeVost Michelle A , Weiss Robert E , Dierst-Davies Rhodri , Shover Chelsea L , Landovitz Raphael J , Beniasians Corinne , Talan Ali J , Flynn Risa P , Krysiak Robyn , McLaughlin Kayla , Bolan Robert K 
Published: February 2018

BackgroundPre-exposure prophylaxis (PrEP) is an effective method for reducing HIV incidence among at-risk populations. However, concerns exist over the potential for an increase in STIs following PrEP initiation. The objective of this study is to compare the STI incidence before and after PrEP initiation within subjects among a cohort of men who have sex with men in Los Angeles, California.MethodsThe present study used data from patients who initiated PrEP services at the Los Angeles LGBT Center between October 2015 and October 2016 (n=275). A generalised linear mixed model was used with a case-crossover design to determine if there was a significant difference in STIs within subjects 365 days before (before-PrEP period) and 365 days after PrEP initiation (after-PrEP period).ResultsIn a generalised linear mixed model, there were no significant differences in urethral gonorrhoea (P=0.95), rectal gonorrhoea (P=0.33), pharyngeal gonorrhoea (P=0.65) or urethral chlamydia (P=0.71) between periods. There were modest increases in rectal chlamydia (rate ratio (RR) 1.83; 95% CI 1.13 to 2.98; P=0.01) and syphilis diagnoses (RR 2.97; 95% CI 1.23 to 7.18; P=0.02).ConclusionsThere were significant increases in rectal chlamydia and syphilis diagnoses when comparing the periods directly before and after PrEP initiation. However, only 28% of individuals had an increase in STIs between periods. Although risk compensation appears to be present for a segment of PrEP users, the majority of individuals either maintain or decrease their sexual risk following PrEP initiation.
Myocardial depression in a calf with septic shock
Authors: Naseri Amir , Turgut Kursad , Sen Ismail , Ider Merve , Akar Aybars 
Published: February 2018

A 10‐day‐old, 32‐kg Simmental heifer calf was presented with a 2‐day history of diarrhoea and anorexia. The diagnosis of septic shock was based on the presence of severe sepsis and hypotension that could not be reversed with fluid resuscitation. Echocardiographic findings included a hypokinetic left ventricle with decreased left ventricle ejection fraction, stroke volume and cardiac index. The end‐systolic volume index (ESVI) was elevated to 36.14 ml/m2 and a depressed end‐diastolic volume index (EDVI) (51.31 ml/m2). Left ventricular depression was normalised 24 hours after resuscitation. It was concluded that myocardial depression could be reversible in the calf with septic shock; however, according to the postresuscitation echocardiographic findings, a decreased ESVI suggests vasomotor dysregulation and a decreased EDVI suggests alterations in vascular permeability. These were the major implications of sepsis and resulted in multiple organ dysfunction and death.
Quantum cost optimized design of 4-bit reversible universal shift register using reduced number of logic gate
Authors: Maity H. , Biswas A. , Bhattacharjee A. K. , Pal A. 
Published: February 2018

In this paper, we have proposed the design of quantum cost (QC) optimized 4-bit reversible universal shift register (RUSR) using reduced number of reversible logic gates. The proposed design is very useful in quantum computing due to its low QC, less no. of reversible logic gate and less delay. The QC, no. of gates, garbage outputs (GOs) are respectively 64, 8 and 16 for proposed work. The improvement of proposed work is also presented. The QC is 5.88% to 70.9% improved, no. of gate is 60% to 83.33% improved with compared to latest reported result.
Targeting Polo-like Kinase 1 by a Novel Pyrrole-Imidazole Polyamide–Hoechst Conjugate Suppresses Tumor Growth In Vivo
Authors: Liu Ke , Fang Lijing , Sun Haiyan , Pan Zhengyin , Zhang Jianchao , Chen Juntao , Shao Ximing , Wang Wei , Tan Yuanyan , Ding Zhihao , Ao Lijiao , Wu Chunlei , Liu Xiaoqi , Li Huashun , Wang Rui , Su Wu , Li Hongchang 
Published: February 2018

Abstract
The serine/threonine kinase Polo-like kinase 1 (Plk1) plays a pivotal role in cell proliferation and has been validated as a promising anticancer drug target. However, very limited success has been achieved in clinical applications using existing Plk1 inhibitors, due to lack of sufficient specificity toward Plk1. To develop a novel Plk1 inhibitor with high selectivity and efficacy, we designed and synthesized a pyrrole-imidazole polyamide–Hoechst conjugate, PIP3, targeted to specific DNA sequence in the PLK1 promoter. PIP3 could specifically inhibit the cell cycle–regulated Plk1 expression and consequently retard tumor cell growth. Cancer cells treated with PIP3 exhibited severe mitotic defects and increased apoptosis, whereas normal cells were not affected by PIP3 treatment. Furthermore, subcutaneous injection of PIP3 into mice bearing human cancer xenografts induced significant tumor growth suppression with low host toxicity. Therefore, PIP3 exhibits the potential as an effective agent for targeted cancer therapy. Mol Cancer Ther; 17(5); 988–1002. ©2018 AACR.
Inhibition of the Histone H3K27 Demethylase UTX Enhances Tumor Cell Radiosensitivity
Authors: Rath Barbara H. , Waung Isabella , Camphausen Kevin , Tofilon Philip J. 
Published: February 2018

AbstractThe processes mediating the repair of DNA double-strand breaks (DSB) are critical determinants of radiosensitivity and provide a source of potential targets for tumor radiosensitization. Among the events required for efficient DSB repair are a variety of post-translational histone modifications, including methylation. Because trimethylation of histone H3 on lysine 27 (H3K27me3) has been associated with chromatin condensation, which can influence DSB repair, we determined the effects of radiation on H3K27me3 levels in tumor and normal cell lines. Irradiation of tumor cells resulted in a rapid loss of H3K27me3, which was prevented by the siRNA-mediated knockdown of the H3K27 demethylase UTX. Knockdown of UTX also enhanced the radiosensitivity of each tumor cell line. Treatment of tumor cells with the H3K27 demethylase inhibitor GSKJ4 immediately before irradiation prevented the radiation-induced decrease in H3K27me3 and enhanced radiosensitivity. As determined by neutral comet analysis and γH2AX expression, this GSKJ4 treatment protocol inhibited the repair of radiation-induced DSBs. Consistent with in vitro results, treatment of mice bearing leg tumor xenografts with GSKJ4 significantly enhance radiation-induce tumor growth delay. In contrast with results generated from tumor cell lines, radiation had no effect on H3K27me3 levels in normal fibroblast cell lines and GSKJ4 did not enhance their radiosensitivity. These data suggest that H3K27me3 demethylation contributes to DSB repair in tumor cells and that UTX, the demethylase responsible, provides a target for selective tumor cell radiosensitization. Mol Cancer Ther; 17(5); 1070–8. ©2018 AACR.
Community treatment orders increase community care and delay readmission while in force: Results from a large population-based study
Authors: Harris Anthony , Chen Wendy , Jones Sharon , Hulme Melissa , Burgess Philip , Sara Grant 
Published: February 2018

Objective: There is debate about the effectiveness of community treatment orders in the management of people with a severe mental illness. While some case–control studies suggest community treatment orders reduce hospital readmissions, three randomised controlled trials find no effects. These randomised controlled trials measure outcomes over a longer period than the community treatment order duration and assess the combined effectiveness of community treatment orders both during and after the intervention. This study examines the effectiveness of community treatment orders in a large population-based sample, restricting observation to the period under a community treatment order. Methods: All persons ( n = 5548) receiving a community treatment order in New South Wales, Australia, over the period 2004–2009 were identified. Controls were matched using a propensity score based on demographic, clinical and prior care variables. A baseline period equal to each case’s duration of treatment was constructed. Treatment effects were compared using zero-inflated negative binomial regression, adjusting for demographics, clinical characteristics and pre-community treatment order care. Results: Compared to matched controls, people on community treatment orders were less likely to be readmitted (odds ratio = 0.90, 95% confidence interval = [0.84, 0.97]) and had a significantly longer time to their first readmission (incidence rate ratio = 1.47, 95% confidence interval = [1.36, 1.58]), fewer hospital admissions (incidence rate ratio = 0.90, 95% confidence interval = [0.84, 0.96]) and more days of community care (incidence rate ratio = 1.55, 95% confidence interval = [1.51, 1.59]). Increased community care and delayed first admission were found for all durations of community treatment order care. Reduced odds of readmission were limited to people with 6 months or less of community treatment order care, and reduced number of admissions and days in hospital to people with prolonged (>24 months) community treatment order care. Conclusion: In this large population-based study, community treatment orders increase community care and delay rehospitalisation while they are in operation. Some negative findings in this field may reflect the use of observation periods longer than the period of active intervention.
Bacteraemia and Upper Gastrointestinal Fibre-Endoscopy
Authors: Kirk A , Graham-Brown R , Perinpanayagam R M , Smith R G , Barnardo D E 
Published: February 2018

A prospective study of fifty-two patients undergoing fibreoptic upper gastrointestinal endoscopy was carried out in order to determine whether bacteraemia was a significant risk. Aerobic and anaerobic blood cultures were performed before, during and after endoscopy. Cultures were also taken from lesions (if any found) in the oesophagus, stomach or duodenum. No significant bacteraemia was identified, and bacterial growth was found in only one upper gastrointestinal lesion.
Diagnostic Reliability of Pleural Fluid Protein Estimation
Authors: Melsom R D 
Published: February 2018

In a series of 86 elderly patients the measurement of pleural fluid protein was found to be of limited value in distinguishing exudates from transudates, although levels above 49 gil were all found to be exudates. However, the difference in mean pleural fluid proteins in the two groups when analysed statistically was highly significant. In addition, there was a significant difference between the means within the exudative group when analysed in groups according to aetiology. Correcting for plasma albumin values did not improve discrimination between exudates and transudates despite a significant correlation between albumin and pleural fluid protein concentration.
A Novel Pathologic Variant in OTOF in an Iranian Family Segregating Hereditary Hearing Loss
Authors: Tabatabaiefar Mohammad Amin , Pourreza Mohammad Reza , Tahmasebi Parisa , Saki Nader , Hashemzadeh Chaleshtori Morteza , Salehi Rasoul , Mohammadi‐asl Javad 
Published: February 2018

ObjectiveHearing loss (HL) is the most common sensory‐neural defect and the most heterogeneous trait in humans, with the involvement of >100 genes, which make a molecular diagnosis problematic. Next‐generation sequencing (NGS) is a new strategy that can overcome this problem.Study DesignDescriptive experimental study.SettingDiagnostic laboratory.Subjects and MethodsA comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in a family with multiple individuals with HL. As the first tier, GJB2 was sequenced, and genetic linkage analysis of DFNB1A/B was performed to rule out the most common cause of the disease. Targeted NGS was used to unravel the molecular etiology of the disease in the HL‐associated genes in the proband. Two homozygous variants remained in OTOF after proper filtration. Cosegregation and in silico analysis were done. Preimplantation genetic diagnosis (PGD) was accomplished via linkage analysis and direct sequencing of the pathogenic variant.ResultsClinical evaluations suggested autosomal recessive nonsyndromic HL. Two homozygous variants, c.367G>A (p.Gly123Ser) and c.1392+1G>A, were identified in cis status. c.1392+1G>A met the criteria for being pathogenic according to the variant interpretation guideline of the American College of Medical Genetics and Genomics. PGD was successfully performed to prevent the recurrence of the disease in the related family.ConclusionA novel OTOF mutation causing HL was identified. Here, we report the effectiveness of the combined application of targeted NGS and PGD in diagnosis and prevention of hereditary HL.