bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated systems approach defines the antiviral pathways conferring protection by the RV144 HIV vaccine
Authors: Fourati Slim , Ribeiro Susan Pereira , Blasco Tavares Pereira Lopes Filipa , Talla Aarthi , Lefebvre Francois , Cameron Mark , Kaewkungwal J. , Pitisuttithum P. , Nitayaphan S. , Rerks-Ngarm S. , Kim Jerome H. , Thomas Rasmi , Gilbert Peter B. , Tomaras Georgia D. , Koup Richard A. , Michael Nelson L. , McElrath M. Juliana , Gottardo Raphael , Sékaly Rafick-Pierre 
Published: February 2019

AbstractThe RV144 vaccine trial showed reduced risk of HIV-1 acquisition by 31.2%, although mechanisms that led to protection remain poorly understood. Here we identify transcriptional correlates for reduced HIV-1 acquisition after vaccination. We assess the transcriptomic profile of blood collected from 223 participants and 40 placebo recipients. Pathway-level analysis of HIV-1 negative vaccinees reveals that type I interferons that activate the IRF7 antiviral program and type II interferon-stimulated genes implicated in antigen-presentation are both associated with a reduced risk of HIV-1 acquisition. In contrast, genes upstream and downstream of NF-κB, mTORC1 and host genes required for viral infection are associated with an increased risk of HIV-1 acquisition among vaccinees and placebo recipients, defining a vaccine independent association with HIV-1 acquisition. Our transcriptomic analysis of RV144 trial samples identifies IRF7 as a mediator of protection and the activation of mTORC1 as a correlate of the risk of HIV-1 acquisition.
Prenatal circulating microRNA signatures of foetal Down syndrome
Authors: Zbucka-Kretowska Monika , Niemira Magdalena , Paczkowska-Abdulsalam Magdalena , Bielska Agnieszka , Szalkowska Anna , Parfieniuk Ewa , Ciborowski Michal , Wolczynski Slawomir , Kretowski Adam 
Published: February 2019

AbstractThe altered expression pattern of miRNAs might potentially reflect anomalies related to foetal chromosomal aberrations. The aim of the study was to determine the expression level of miRNAs in plasma of pregnant women with foetal Down syndrome (DS). Out of 198 amniocentesis performed at 15–18 weeks of gestation, within a group of 12 patients with foetal DS and 12 patients with uncomplicated pregnancies, who delivered healthy newborns at term, we examined the expression level of 800 miRNAs using the NanoString technology. Our study revealed that there are 6 miRNAs were upregulated (hsa-miR-15a, hsa-let-7d, hsa-miR-142, hsa-miR-23a, hsa-miR-199, hsa-miR-191) and 7 were downregulated (hsa-miR-1290, hsa-miR-1915, hsa-miR30e, hsa-miR-1260, hsa-miR-483, hsa-miR-548, hsa-miR-590) in plasma samples of women with foetal DS syndrome. The genes regulated by identified miRNAs are involved in central nervous system development, congenital abnormalities and heart defects. The results of the present study yielded information on DS-specific miRNA expression signature, which can further help to design a panel of miRNAs as a non-invasive test for DS diagnosis. We believe that identified miRNAs may attend in the pathogenesis of DS and would potentially make a significant role for the future preventive therapies.
A PKA/cdc42 Signaling Axis Restricts Angiogenic Sprouting by Regulating Podosome Rosette Biogenesis and Matrix Remodeling
Authors: MacKeil J. L. , Brzezinska P. , Burke-Kleinman J. , Craig A. W. , Nicol C. J. B. , Maurice D. H. 
Published: February 2019

AbstractAngiogenic sprouting can contribute adaptively, or mal-adaptively, to a myriad of conditions including ischemic heart disease and cancer. While the cellular and molecular systems that regulate tip versus stalk endothelial cell (EC) specification during angiogenesis are known, those systems that regulate their distinct actions remain poorly understood. Pre-clinical and clinical findings support sustained adrenergic signaling in promoting angiogenesis, but links between adrenergic signaling and angiogenesis are lacking; importantly, adrenergic agents alter the activation status of the cAMP signaling system. Here, we show that the cAMP effector, PKA, acts in a cell autonomous fashion to constitutively reduce the in vitro and ex vivo angiogenic sprouting capacity of ECs. At a cellular level, we observed that silencing or inhibiting PKA in human ECs increased their invasive capacity, their generation of podosome rosettes and, consequently, their ability to degrade a collagen matrix. While inhibition of either Src-family kinases or of cdc42 reduced these events in control ECs, only cdc42 inhibition, or silencing, significantly impacted them in PKA(Cα)-silenced ECs. Consistent with these findings, cell-based measurements of cdc42 activity revealed that PKA activation inhibits EC cdc42 activity, at least in part, by promoting its interaction with the inhibitory regulator, guanine nucleotide dissociation inhibitor-α (RhoGDIα).
Overexpression of thermostable meso-diaminopimelate dehydrogenase to redirect diaminopimelate pathway for increasing L-lysine production in Escherichia coli
Authors: Xu Jian-Zhong , Ruan Hao-Zhe , Liu Li-Ming , Wang Lu-Ping , Zhang Wei-Guo 
Published: February 2019

AbstractDehydrogenase pathway, one of diaminopimelate pathway, is important to the biosynthesis of L-lysine and peptidoglycan via one single reaction catalyzed by meso-diaminopimelate dehydrogenase (DapDH). In this study, the thermostable DapDH was introduced into diaminopimelate pathway that increased the final titer (from 71.8 to 119.5 g/L), carbon yield (from 35.3% to 49.1%) and productivity (from 1.80 to 2.99 g/(L∙h)) of L-lysine by LATR12-2∆rpiB::ddhSt in fed-batch fermentation. To do this, the kinetic properties and the effects of different DapDHs on L-lysine production were investigated, and the results indicated that overexpression of StDapDH in LATR12-2 was beneficial to construct an L-lysine producer with good productive performance because it exhibited the best of kinetic characteristics and optimal temperature as well as thermostability in reductive amination. Furthermore, ammonium availability was optimized, and found that 20 g/L of (NH4)2SO4 was the optimal ammonium concentration for improving the efficiency of L-lysine production by LATR12-2∆rpiB::ddhSt. Metabolomics analysis showed that introducing the StDapDH significantly enhanced carbon flux into pentose phosphate pathway and L-lysine biosynthetic pathway, thus increasing the levels of NADPH and precursors for L-lysine biosynthesis. This is the first report of a rational modification of diaminopimelate pathway that improves the efficiency of L-lysine production through overexpression of thermostable DapDH in E. coli.
Species distribution models throughout the invasion history of Palmer amaranth predict regions at risk of future invasion and reveal challenges with modeling rapidly shifting geographic ranges
Authors: Briscoe Runquist Ryan D. , Lake Thomas , Tiffin Peter , Moeller David A. 
Published: February 2019

AbstractPalmer amaranth (Amaranthus palmeri) is an annual plant native to the desert Southwest of the United States and Mexico and has become invasive and caused large economic losses across much of the United States. In order to examine the temporal and spatial dynamics of past invasion, and to predict future invasion, we developed a broad array of species distribution models (SDMs). In particular, we constructed sequential SDMs throughout the invasion history and asked how well those predicted future invasion (1970 to present). We showed that invasion occurred from a restricted set of environments in the native range to a diverse set in the invaded range. Spatial autocorrelation analyses indicated that rapid range expansion was facilitated by stochastic, long-distance dispersal events. Regardless of SDM approach, all SDMs built using datasets from early in the invasion (1970–2010) performed poorly and failed to predict most of the current invaded range. Together, these results suggest that climate is unlikely to have influenced early stages of range expansion. SDMs that incorporated data from the most recent sampling (2011–2017) performed considerably better, predicted high suitability in regions that have recently become invaded, and identified mean annual temperature as a key factor limiting northward range expansion. Under future climates, models predicted both further northward range expansion and significantly increased suitability across large portions of the U.S. Overall, our results indicate significant challenges for SDMs of invasive species far from climate equilibrium. However, our models based on recent data make more robust predictions for northward range expansion ofA. palmeriwith climate change.
A Haemophilus sp. dominates the microbiota of sputum from UK adults with non-severe community acquired pneumonia and chronic lung disease
Authors: Wootton Daniel G. , Cox Michael J. , Gloor Gregory B. , Litt David , Hoschler Katja , German Esther , Court Joanne , Eneje Odiri , Keogan Lynne , Macfarlane Laura , Wilks Sarah , Diggle Peter J. , Woodhead Mark , Moffatt Miriam F. , Cookson William O. C. , Gordon Stephen B. 
Published: February 2019

AbstractThe demographics and comorbidities of patients with community acquired pneumonia (CAP) vary enormously but stratified treatment is difficult because aetiological studies have failed to comprehensively identify the pathogens. Our aim was to describe the bacterial microbiota of CAP and relate these to clinical characteristics in order to inform future trials of treatment stratified by co-morbidity. CAP patients were prospectively recruited at two UK hospitals. We used 16S rRNA gene sequencing to identify the dominant bacteria in sputum and compositional data analysis to determine associations with patient characteristics. We analysed sputum samples from 77 patients and found a Streptococcus sp. and a Haemophilus sp. were the most relatively abundant pathogens. The Haemophilus sp. was more likely to be dominant in patients with pre-existing lung disease, and its relative abundance was associated with qPCR levels of Haemophilus influenzae. The most abundant Streptococcus sp. was associated with qPCR levels of Streptococcus pneumoniae but dominance could not be predicted from clinical characteristics. These data suggest chronic lung disease influences the microbiota of sputum in patients with CAP. This finding could inform a trial of stratifying empirical CAP antibiotics to target Haemophilus spp. in addition to Streptococcus spp. in those with chronic lung disease.
Top-down Mass Spectrometry Analysis of Human Serum Autoantibody Antigen-Binding Fragments
Authors: Wang Zhe , Liu Xiaowen , Muther Jennifer , James Judith A. , Smith Kenneth , Wu Si 
Published: February 2019

AbstractDetecting autoimmune diseases at an early stage is crucial for effective treatment and disease management to slow disease progression and prevent irreversible organ damage. In many autoimmune diseases, disease-specific autoantibodies are produced by B cells in response to soluble autoantigens due to defects in B cell tolerance mechanisms. Autoantibodies accrue early in disease development, and several are so disease-specific they serve as classification criteria. In this study, we established a high-throughput, sensitive, intact serum autoantibody analysis platform based on the optimization of a one dimensional ultra-high-pressure liquid chromatography top-down mass spectrometry platform (1D UPLC-TDMS). This approach has been successfully applied to a 12 standard monoclonal antibody antigen-binding fragment (Fab) mixture, demonstrating the feasibility to separate and sequence intact antibodies with high sequence coverage and high sensitivity. We then applied the optimized platform to characterize total serum antibody Fabs in a systemic lupus erythematosus (SLE) patient sample and compared it to healthy control samples. From this analysis, we show that the SLE sample has many dominant antibody Fab-related mass features unlike the healthy controls. To our knowledge, this is the first top-down demonstration of serum autoantibody pool analysis. Our proposed approach holds great promise for discovering novel serum autoantibody biomarkers that are of interest for diagnosis, prognosis, and tolerance induction, as well as improving our understanding of pathogenic autoimmune processes.
Brg1 promotes liver regeneration after partial hepatectomy via regulation of cell cycle
Authors: Wang Baocai , Kaufmann Benedikt , Engleitner Thomas , Lu Miao , Mogler Carolin , Olsavszky Victor , Öllinger Rupert , Zhong Suyang , Geraud Cyrill , Cheng Zhangjun , Rad Roland R. , Schmid Roland M. , Friess Helmut , Hüser Norbert , Hartmann Daniel , von Figura Guido 
Published: February 2019

AbstractBrahma-related gene 1 (Brg1), a catalytic subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, is known to be involved in proliferative cell processes. Liver regeneration is initiated spontaneously after injury and leads to a strong proliferative response. In this study, a hepatocyte-specific Brg1 gene knockout mouse model was used to analyse the role of Brg1 in liver regeneration by performing a 70% partial hepatectomy (PH). After PH, Brg1 was significantly upregulated in wildtype mice. Mice with hepatocyte-specific Brg1 gene knockout showed a significantly lower liver to body weight ratio 48 h post-PH concomitant with a lower hepatocellular proliferation rate compared to wildtype mice. RNA sequencing demonstrated that Brg1 controlled hepatocyte proliferation through the regulation of the p53 pathway and several cell cycle genes. The data of this study reveal a crucial role of Brg1 for liver regeneration by promoting hepatocellular proliferation through modulation of cell cycle genes and, thus, identify Brg1 as potential target for therapeutic approaches.
Clinicopathological correlation of ARID1A status with HDAC6 and its related factors in ovarian clear cell carcinoma
Authors: Yano Mitsutake , Katoh Tomomi , Miyazawa Mariko , Miyazawa Masaki , Ogane Naoki , Miwa Maiko , Hasegawa Kosei , Narahara Hisashi , Yasuda Masanori 
Published: February 2019

AbstractOvarian clear cell carcinoma (OCCC) is associated with a frequent loss in ARID1A function. ARID1A reportedly suppresses histone deacetylase (HDAC)6 in OCCC directly. Here, we evaluated the clinical significance of HDAC6 expression and its related factors in terms of ARID1A status. Immunohistochemical expression of HDAC6, hypoxia inducible factors-1α (HIF-1α), programmed death-1 ligand (PD-L1), CD44 (cancer stem cell marker), and ARID1A was analysed for 106 OCCC patients. High nuclear HDAC6 expression correlated with patient death (p = 0.038). In the multivariate analysis of overall survival, surgical status (complete or incomplete resection) (hazard ratio (HR) = 17.5; p = <0.001), HDAC6 nuclear expression (HR = 1.68; p = 0.034), and PD-L1 expression (HR = 1.95; p = 0.022) were the independent prognostic factors. HDAC6 upregulation and ARID1A loss did not necessarily occur simultaneously. High HDAC6 expression was associated with poor prognosis in OCCC with ARID1A loss; this was not observed without ARID1A loss. HDAC6 expression showed a significant positive correlation with HIF-1α, PD-L1, and CD44. In OCCC, HDAC6 involvement in prognosis depended on ARID1A status. HDAC6 also led to immuno- and hypoxia- tolerance and cancer stem cell phenotype. HDAC6 is a promising therapeutic target for OCCC with loss of ARID1A.
Novel mutations in the kinase domain of BCR-ABL gene causing imatinib resistance in chronic myeloid leukemia patients
Authors: Chandrasekhar Chodimella , Kumar Pasupuleti Santhosh , Sarma Potukuchi Venkata Gurunadha Krishna 
Published: February 2019

AbstractMutations in the drug binding region of BCR-ABL lead to imatinib resistance during the management of chronic myeloid leukemia (CML). In our study, 62 Philadelphia positive (Ph+) CML patients showing conspicuous expression of BCR-ABL gene were treated with imatinib. At the end of 3 months, 21/62 (33.87%) patients did not obtain complete hematological response (CHR) and also showed no significant decrease in BCR-ABL gene expression. In all the imatinib-resistant patients BCR-ABL gene was PCR amplified and sequenced. The sequence analysis showed four novel missense mutations p.(Leu301Ile), p.(Tyr320His), p.(Glu373Asp), p.(Asp381Asn) and six already reported mutations p.(Val256Gly), p.(Thr315Ile), p.(Gly250Glu), p.(Tyr253His), p.(Phe317Leu), p.(Met351Thr) which contributed in the formation of inactive enzyme and also two novel frameshift mutations p.(Glu281*) and p.(Tyr393*), which resulted in truncated protein formation. Further, the structural analysis revealed all these mutations affected P-loop, gatekeeper, catalytic and activation loop domain regions of the enzyme causing poor imatinib binding in the ATP region. The primary intention of the study was to find out the mutations in the BCR-ABL gene causing imatinib resistance. This study highlights the need for BCR-ABL gene sequence analysis to detect the mutations in CML patients in order to properly guide the therapy.
Nullifying phosphatidic acid effect and controlling phospholipase D associated browning in litchi pericarp through combinatorial application of hexanal and inositol
Authors: Bhushan Bharat , Kumar Satish , Mahawar Manoj Kumar , Jalgaonkar Kirti , Dukare Ajinath Shridhar , Bibwe Bhushan , Meena Vijay Singh , Negi Narender , Narwal Rajesh Kumari , Pal Ajay 
Published: February 2019

AbstractThe role of phospholipid modification initiated by phospholipase D (PLD) in enzymatic browning has been revoked through this study. Various alcohols and aldehydes were tried to read out their PLD controlling behaviour. Based on in-vitro results, reagents like hexanal and inositol were used to regulate PLD activity of litchi fruit stored at ambient temperature and their effects on fruit quality and physiological characteristics were also investigated. The results showed that combinatorial chemical treatment was successful in maintaining freshness of fruit through delayed physiological loss in weight and hence maintaining firmness. Combinatorial treated fruit had lower browning index than control by day 7. This novel treatment also maintained comparable levels of total phenolics and lowered the level of malondialdehyde. Evaluation of antioxidative enzymatic profile also confirmed the alleviation of oxidative stress of litchi fruit at ambient temperature. Thus, this strategy of enzyme regulation could play a vital role in overall quality maintenance of litchi fruit.
Tunable multiple Fano resonance employing polarization-selective excitation of coupled surface-mode and nanoslit antenna resonance in plasmonic nanostructures
Authors: Liu Jietao , Liu Zhi , Hu Haifeng 
Published: February 2019

AbstractModeling and tailoring of multispectral Fano resonance in plasmonic system employing nanoslit-antenna array is demonstrated and investigated. Efficient control of the multiple Fano profile can be manipulated, where the overall spectral is achieved by the separate contributions from the fundamental subgroups plasmonic resonance eigenstates. A polarization-selective strategy on nano-antennas resonance is proposed to shed light on the efficient manipulation of the multiple Fano resonances. Theory prediction of TM−1 surface mode excited in the system and thorough dispersion analysis of the supported Bloch modes provides evidence for understanding the origin of the transmission spectra. Compact nanophotonics planar optical linear-polarizer in the proposed nanostructure is investigated and demonstrated, where flexible Fano resonance control over the profile, linewidth and spectral contrast is appealing for applications such as sensing, switches and multifunctional nanophotonics devices.
Automated behavioural analysis reveals the basic behavioural repertoire of the urochordate Ciona intestinalis
Authors: Rudolf Jerneja , Dondorp Daniel , Canon Louise , Tieo Sonia , Chatzigeorgiou Marios 
Published: February 2019

AbstractQuantitative analysis of animal behaviour in model organisms is becoming an increasingly essential approach for tackling the great challenge of understanding how activity in the brain gives rise to behaviour. Here we used automated image-based tracking to extract behavioural features from an organism of great importance in understanding the evolution of chordates, the free-swimming larval form of the tunicate Ciona intestinalis, which has a compact and fully mapped nervous system composed of only 231 neurons. We analysed hundreds of videos of larvae and we extracted basic geometric and physical descriptors of larval behaviour. Importantly, we used machine learning methods to create an objective ontology of behaviours for C. intestinalis larvae. We identified eleven behavioural modes using agglomerative clustering. Using our pipeline for quantitative behavioural analysis, we demonstrate that C. intestinalis larvae exhibit sensory arousal and thigmotaxis. Notably, the anxiotropic drug modafinil modulates thigmotactic behaviour. Furthermore, we tested the robustness of the larval behavioural repertoire by comparing different rearing conditions, ages and group sizes. This study shows that C. intestinalis larval behaviour can be broken down to a set of stereotyped behaviours that are used to different extents in a context-dependent manner.
Cell Type-Specific Interferon-γ-mediated Antagonism of KSHV Lytic Replication
Authors: Park Mi-Kyung , Cho Hyejeong , Roh Seong Woon , Kim Seong-Jun , Myoung Jinjong 
Published: February 2019

AbstractKaposi’s sarcoma-associated herpesvirus (KSHV) is causally associated with several malignant tumors: Kaposi’s sarcoma (KS), multicentric Castleman’s disease (MCD), and primary effusion lymphoma (PEL). KS remains the most common AIDS-related malignancy since the AIDS epidemic and thus has been extensively studied. KS is characterized as an angioproliferative disease with massive immune cell infiltration at the early stage. High levels of proinflammatory cytokines and growth factors are found in KS lesions, and their involvement in the survival and growth of tumor cells has been well characterized. However, little is known about the role of the inflammatory microenvironment in the regulation of KSHV gene expression and/or viral replication. In the present study, we demonstrated that IFN-γ and TNF-α profoundly inhibited KSHV progeny production in primary human lymphatic endothelial cells (LECs) as well as induced KSHV-producer cells (iSLK.219) with doxycycline. Of note, IFN-γ inhibited overall KSHV gene expression, while the effects of TNF-α were confined to a selected set of genes, which were also downregulated by IFN-γ. The addition of IFN-γ up to 36 hr after induction of viral lytic replication was effective in terms of the inhibition of infectious virion production, suggesting that its inhibitory effect is exerted at the early stages of KSHV life cycle. We believe these data have potentially important implications for rationalizing a therapeutic agent to treat KSHV-induced tumors in which lytic replication plays a critical role in their pathogenesis: KS and MCD.