bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression of ERV3-1 in Leukocytes of Acute Myelogenous Leukemia Patients
Authors: Nakagawa So , Kawashima Masaharu , Miyatake Yuji , Kudo Kai , Kotaki Ryutaro , Ando Kiyoshi , Kotani Ai 
Published: September 2020

AbstractAcute myelogenous leukemia (AML) is one of the major hematological malignancies. In the human genome, several have been found to originate from retroviruses, and some of which are involved in progression of various cancers. Hence, to investigate whether retroviral-like genes are associated with the development of AML, we conducted a transcriptome sequencing analysis of 12 retroviral-like genes of 150 AML patients using The Cancer Genome Atlas database. We found high expression of ERV3-1, an envelope gene of endogenous retrovirus group 3 member 1. In particular, blood and bone marrow cells of the myeloid lineage in AML patients, exhibited higher expression of ERV3-1 than those of the monocytic AML lineage. We also examined the protein expression of ERV3-1 by immunohistochemical analysis and found expression of ERV3-1 protein in 7 out of 12 AML patients, with a particular concentration observed at the membrane of some leukemic cells. Transcriptome analysis further suggested that upregulated ERV3-1 expression may be associated with chromosome 8 trisomy as anomaly was found to be more common among the high expression group compared to the low expression group. However, this finding was not corroborated by the immunohistochemical data. This discrepancy may have been caused, in part, by the small number of samples analyzed in this study. Although the precise associated molecular mechanisms remain unclear, our results suggest that ERV3-1 may be involved in AML development.HighlightsExpression of 12 retroviral-like genes in the human genome were analyzed using transcriptome data of 150 acute myelogenous leukemia (AML) patients.ERV3-1, an envelope gene of endogenous retrovirus group 3 member 1, was found to uniquely show high expression level.Morphologic characteristics and chromosomal abnormalities are found to be related with the expression of ERV3-1.
Introduction of two prolines and removal of the polybasic cleavage site leads to optimal efficacy of a recombinant spike based SARS-CoV-2 vaccine in the mouse model
Authors: Amanat Fatima , Strohmeier Shirin , Rathnasinghe Raveen , Schotsaert Michael , Coughlan Lynda , García-Sastre Adolfo , Krammer Florian 
Published: September 2020

AbstractThe spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the prime target for vaccine development. The spike protein mediates both binding to host cells and membrane fusion and is also so far the only known viral target of neutralizing antibodies. Coronavirus spike proteins are large trimers that are relatively instable, a feature that might be enhanced by the presence of a polybasic cleavage site in the SARS-CoV-2 spike. Exchange of K986 and V987 to prolines has been shown to stabilize the trimers of SARS-CoV-1 and the Middle Eastern respiratory syndrome coronavirus spikes. Here, we test multiple versions of a soluble spike protein for their immunogenicity and protective effect against SARS-CoV-2 challenge in a mouse model that transiently expresses human angiotensin converting enzyme 2 via adenovirus transduction. Variants tested include spike protein with a deleted polybasic cleavage site, the proline mutations, a combination thereof, as well as the wild type protein. While all versions of the protein were able to induce neutralizing antibodies, only the antigen with both a deleted cleavage site and the PP mutations completely protected from challenge in this mouse model.ImportanceA vaccine for SARS-CoV-2 is urgently needed. A better understanding of antigen design and attributes that vaccine candidates need to have to induce protective immunity is of high importance. The data presented here validates the choice of antigens that contain the PP mutation and suggests that deletion of the polybasic cleavage site could lead to a further optimized design.
PAF1 facilitates RNA polymerase II ubiquitination by the Elongin A complex through phosphorylation by CDK12
Authors: Sanchez Gabriel , Barbier Jérôme , Elie Céline , Kiernan Rosemary , Rouquier Sylvie 
Published: September 2020

ABSTRACTThe conserved Polymerase-Associated Factor 1 complex (PAF1C) regulates all stages of the RNA polymerase II (RNAPII) transcription cycle from the promoter to the 3’ end formation site of mRNA encoding genes and has been linked to numerous transcription related processes. Here, we show that PAF1 interacts with Elongin A, a transcription elongation factor as well as a component of a cullin-RING ligase that targets stalled RNAPII for ubiquitination and proteasome-dependent degradation in response to DNA damage or other stresses. We show that, in absence of any induced stress, PAF1 physically interacts with the E3 ubiquitin ligase form of the Elongin A complex and facilitates ubiquitination of RNAPII. We demonstrate that this ubiquitination is dependent of the Ser2 phosphorylation of the RNAPII carboxy-terminal domain (CTD) by CDK12. Our findings highlight a novel unexpected role of PAF1-CDK12 in RNAPII transcription cycle, raising the possibility that the Elongin A ubiquitin ligase plays a role in normal transcription process, and suggest a transcription surveillance mechanism ready to degrade RNAPII if needed.
Identification of novel antiviral drug combinations in vitro and tracking their development
Authors: Ianevski Aleksandr , Yao Rouan , Biza Svetlana , Zusinaite Eva , Männik Andres , Kivi Gaily , Planken Anu , Kurg Kristiina , Tombak Eva-Maria , Ustav Mart , Shtaida Nastassia , Kulesskiy Evgeny , Jo Eunji , Yang Jaewon , Lysvand Hilde , Løseth Kirsti , Oksenych Valentyn , Aas Per Arne , Tenson Tanel , Vitkauskiene Astra , Windisch Marc P. , Fenstad Mona Høysæter , Nordbø Svein Arne , Ustav Mart , Bjørås Magnar , Kainov Denis 
Published: September 2020

AbstractCombination therapies have become a standard for the treatment for HIV and HCV infections. They are advantageous over monotherapies due to better efficacy and reduced toxicity, as well as the ability to prevent the development of resistant viral strains and to treat viral co-infections. Here, we identify several new synergistic combinations against emerging and re-emerging viral infections in vitro. We observed synergistic activity of nelfinavir with investigational drug EIDD-2801 and convalescent serum against SARS-CoV-2 infection in human lung epithelial Calu-3 cells. We also demonstrated synergistic activity of vemurafenib combination with emetine, homoharringtonine, gemcitabine, or obatoclax against echovirus 1 infection in human lung epithelial A549 cells. We also found that combinations of sofosbuvir with brequinar and niclosamide were synergistic against HCV infection in hepatocyte derived Huh-7.5 cells, whereas combinations of monensin with lamivudine and tenofovir were synergistic against HIV-1 infection in human cervical TZM-bl cells. Finally, we present an online resource that summarizes novel and known antiviral drug combinations and their developmental status. Overall, the development of combinational therapies could have a global impact improving the preparedness and protection of the general population from emerging and re-emerging viral threats.
The generation of persister cells is regulated at the initiation of translation by (p)ppGpp
Authors: Molina-Quiroz Roberto C. , Camilli Andrew 
Published: September 2020

AbstractBacterial persistence is a non-heritable phenotypic trait characterized by a dormant state that leads to tolerance to different antibiotics. Several mechanisms contributing to persister cells generation have been identified. Among these, is the signaling molecule (p)ppGpp, but knowledge of how this molecule regulates persister generation is incomplete. Here, we show an increase of the persister fraction of uropathogenicEscherichia coli(UPEC) that correlates with the time of protein synthesis inhibition and a decrease in the availability of antibiotic target. Specifically, the arrest of translation initiation induces bacterial survival to ampicillin and ciprofloxacin in a (p)ppGpp-dependent manner. These findings support a global mechanism of persister cell generation and establish a regulatory role of the (p)ppGpp molecule in this phenomenon.ImportanceThe study of persister cell formation is relevant because this bacterial subpopulation is involved in the emergence of antibiotic resistance and the generation of chronic infections. A role of the (p)ppGpp molecule in the generation of the persister fraction has been described, but the identification of the regulatory mechanism mediated by this alarmone during protein translation and its contribution to persistence has not been described to date. In this work, we show that (p)ppGpp regulates the generation of persister cells at the initiation of the protein synthesis process in UPEC. Our results also suggest that a (p)ppGpp-dependent regulation of translation, might be a global mechanism for the generation of the persister fraction.
Molecular and functional characterization of buffalo nasal epithelial odorant binding proteins and their structural insights byin-silicoand biochemical approach
Authors: Manikkaraja Chidhambaram , Mam Bhavika , Singh Randhir , Nagarathnam Balasubramanian , George Geen , Gulyani Akash , Archunan Govindharaju , Sowdhamini Ramanathan 
Published: September 2020

AbstractThe olfactory system is capable of detecting and distinguishing thousands of environmental odorants that play a key role in reproduction, social behaviours including pheromones influenced classical events. Membrane secretary odorant binding proteins (OBPs) are soluble lipocalins, localized in the nasal membrane of mammals. They bind and carry odorants within the nasal epithelium to putative olfactory transmembrane receptors (ORs). While the existence of OBPs and their significant functions are very well known in insects and laboratory mammals, there is little information about the species-specific OBPs in buffaloes. In fact, the OBP of nasal epithelium has not yet been exploited to develop a suitable technique to detect estrus which is being reported as a difficult task in buffalo. In the present study, using molecular biology and protein engineering approaches, we have cloned six novel OBP isoforms from buffalo nasal epithelium (bnOBPs). Furthermore, 3D model was developed and molecular-docking, dynamics experiments were performed byIn-silicoapproach. In particular, we found four residues (Phe104, Phe134, Phe69 and Asn118) from OBP1a, which had strong binding affinities towards two sex pheromones, specifically oleic acid and p-cresol. We expressed this protein inEscherichia colito examine its involvement in the sex pheromone perception from female buffalo urine and validated through fluorescence quenching studies. Interestingly, fluorescence binding experiments also showed similar strong binding affinities of OBP1a to oleic acid and p-cresol. By using structural data, the binding specificity is also verified by site-directed mutagenesis of the four residues followed by in-vitro binding assays. Our results enable to better understand the functions of different nasal epithelium OBPs in buffaloes. They also lead to improved understanding of the interaction between olfactory proteins and odorants to develop highly selective biosensing devices for non-invasive detection of estrus in buffaloes.
Schlafen family member 5 (SLFN5) regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer
Authors: Martinez Rafael S. , Salji Mark J. , Rushworth Linda , Ntala Chara , Blanco Giovanny Rodriguez , Hedley Ann , Clark William , Peixoto Paul , Hervouet Eric , Renaude Elodie , Kung Sonia H.Y. , Galbraith Laura C.A. , Nixon Colin , Lilla Sergio , MacKay Gillian M. , Fazli Ladan , Sumpton David , Gleave Martin E. , Zanivan Sara , Blomme Arnaud , Leung Hing Y. 
Published: September 2020

AbstractAndrogen-deprivation therapy (ADT) is the standard of care for the treatment of non-resectable prostate cancer (PCa). Despite high treatment efficiency, most patients ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we perform a comparative proteomic analysis of threein vivo,androgen receptor (AR)–driven, orthograft models of CRPC. Differential proteomic analysis reveals that distinct molecular mechanisms, including amino acid (AA) and fatty acid (FA) metabolism, are involved in the response to ADT between the different models. Despite this heterogeneity, we identify SLFN5 as an AR-regulated biomarker in CRPC. SLFN5 expression is high in CRPC tumours and correlates with poor patient outcome.In vivo, SLFN5depletion strongly impairs tumour growth in castrated condition. Mechanistically, SLFN5 interacts with ATF4 and regulates the expression of LAT1, an essential AA transporter. Consequently,SLFN5depletion in CRPC cells decreases intracellular levels of essential AA and impairs mTORC1 signalling in a LAT1-dependent manner.
CRISPRi screens reveal genes modulating yeast growth in lignocellulose hydrolysate
Authors: Gutmann Friederike , Jann Cosimo , Pereira Filipa , Johansson Andreas , Steinmetz Lars M. , Patil Kiran R. 
Published: September 2020

AbstractBackgroundBaker’s yeast is a widely used eukaryotic cell factory, producing a diverse range of compounds including biofuels and fine chemicals. The use of lignocellulose as feedstock offers the opportunity to run these processes in an environmentally sustainable way. However, the required hydrolysis pretreatment of lignocellulosic material releases toxic compounds that hamper yeast growth and consequently productivity.ResultsHere, we employ CRISPR interference inS. cerevisiaeto identify genes modulating fermentative growth in plant hydrolysate and in presence of lignocellulosic toxins. We find that at least one third of hydrolysate-associated gene functions are explained by effects of known toxic compounds, such as the decreased growth ofYAP1orHAA1, or increased growth ofDOT6knock-down strains in hydrolysate.ConclusionOur study confirms previously known genetic elements and uncovers new targets towards designing more robust yeast strains for the utilization of lignocellulose hydrolysate as sustainable feedstock, and, more broadly, paves the way for applying CRISPRi screens to improve industrial fermentation processes.
Disordered phasic relationships between hippocampal place cells, theta, and gamma rhythms in the Ts65Dn mouse model of Down Syndrome
Authors: Heller H.C. , Freeburn A. , Finn D.P. , Munn R.G.K 
Published: September 2020

AbstractDown Syndrome (DS) in humans is caused by trisomy of chromosome 21 and is marked by prominent difficulties in learning and memory. Decades of research have demonstrated that the hippocampus is a key structure in learning and memory, and recent work with mouse models of DS have shown changes in spectral coherence in the field potentials of hippocampus and regions important for executive function such as prefrontal cortex. One of the primary functional differences in DS is thought to be an excess of GABAergic innervation from Medial Septum (MS) to regions such as hippocampus. In these experiments, we probe in detail the activity of region CA1 of the hippocampus usingin vivoelectrophysiology in the Ts65Dn mouse model of DS in comparison to their non-trisomic 2N littermates. We find changes in hippocampal phenomenology that suggest that MS output, which drives theta rhythm in the hippocampus, is strongly altered. Moreover, we find that this change affects the phasic relationship of both CA1 place cells and gamma rhythms to theta. Since the phasic relationship of both of these aspects of hippocampal phenomenology to theta are thought to be critical for the segregation of encoding and retrieval epochs within hippocampus, it is likely that these changes are the neural substrates of the learning and memory deficits seen both in human DS and animal models such as Ts65Dn.
TIP family aquaporins play role in chloroplast osmoregulation and photosynthesis
Authors: Beebo Azeez , Zia Ahmad , Kinzel Christopher R. , Herdean Andrei , Bouhidel Karim , Kirchhoff Helmut , Schoefs Benoît , Spetea Cornelia 
Published: September 2020

SUMMARYPhotosynthetic oxygen evolution by photosystem II requires water supply into the chloroplast to reach the thylakoid lumen. A rapid water flow is also required into the chloroplast for optimal oxygen evolution and to overcome osmotic stress. The mechanisms governing water transport in chloroplasts are largely unexplored. Previous proteomics indicated the presence of three aquaporins from the tonoplast intrinsic protein (TIP) family, TIP1;1, TIP1;2 and TIP2;1, in chloroplast membranes ofArabidopsis thaliana. Here we revisited their location and studied their role in chloroplasts. Localization experiments indicated that TIP2;1 resides in the thylakoid, whereas TIP1;2 is present in both thylakoid and envelope membranes. Mutants lacking TIP1;2 and/or TIP2;1 did not display a macroscopic phenotype when grown under standard conditions. The mutant chloroplasts and thylakoids underwent less volume changes than the corresponding wild type preparations upon osmotic treatment and in the light. Significantly reduced rates of photosynthetic electron transport were obtained in the mutant leaves, with implications on the CO2fixation rates. However, electron transport rates did not significantly differ between mutants and wild type when isolated thylakoids were examined. Less acidification of the thylakoid lumen was measured in mutants thylakoids, resulting in a slower induction of delta pH-dependent photoprotective mechanisms. These results identify TIP1;2 and TIP2;1 as chloroplast proteins and highlight their importance for osmoregulation and optimal photosynthesis. A third aquaporin, TIP1;1, is present in the chloroplast envelope, and may play role in photosynthesis under excessive light conditions, as based on the weak photosynthetic phenotype of its mutant.
Understanding extended information seeking
Authors: Zha Xianjin , Huang Chengsong , Yan Yalan , Yan Guanxiang , Wang Xue , Zhang Kun 
Published: September 2020

PurposeThis study aims to explore the mechanisms of extended information seeking, which is the combination of extended information technologies (IT) use behavior and information-seeking behavior. The purpose is to identify the factors that shape extended information seeking from the perspectives of psychological empowerment and attachment.Design/methodology/approachA research model was developed based on prior theory and literature. Survey data were collected, and the partial least squares (PLS) structural equation modeling was used to verify the research model.FindingsPsychological empowerment is a well-constructed second-order construct, having a larger positive effect on extended information seeking. Digital libraries attachment has a positive effect on extended information seeking.Practical implicationsAccessing digital libraries does not mean using digital libraries effectively. Managers of digital libraries should design various specific information activities to help users enhance psychological empowerment. They should provide more available and responsive services for users to enhance digital libraries attachment.Originality/valueDrawing on the adaptive structuration theory, this study examines extended information seeking by combining extended use of digital libraries and information seeking, presenting a new lens for digital library and information seeking research.
Management response to negative comments, psychological distance and product nature: a consumer perspective
Authors: Zheng Chundong , Yuan Liping , Bian Xuemei , Wang Han , Huang Lei 
Published: September 2020

PurposeManagement response to consumer comments has become a widely adopted marketing strategy to address the undesirable effects caused by negative remarks. Yet, when and what management response is more effective and under what circumstances remains under-researched. This study aims to fill this gap.Design/methodology/approachIn three experiments using five different products, the authors manipulate psychological construal level (psychological distance: distant vs proximal) and management response (response of primary vs secondary features) and thereafter assess their bearings on consumer psychological and behavioral reaction toward products of two distinctive natures (hedonic vs utilitarian).FindingsAt a psychological distance, consumers show a preferable reaction to management response of primary over secondary features. In contrast, when the psychological distance is proximal, consumers react more positively to management response of secondary than primary features. In addition, these effects vary as a function of product nature, hedonic vs utilitarian.Research limitations/implicationsThe findings of this research bring a significant contribution to marketing communication literature and extend the construal level theory.Practical implicationsA better understanding of the relative effectiveness of distinct types of management response to negative consumer comments is essential for more targeted and effective marketing strategies.Originality/valueLittle research has documented the effects of distinct types of management response. How psychological distance might underpin these effects has not been explored. In addition, whether the interaction effect of management response and psychological distance varies with differences in product nature, namely, hedonic and utilitarian, remains unanswered until this research.
Instruments for investment protection when structuring Islamic venture capital
Authors: Ibrahim Abdul-Jalil , Kahf Monzer 
Published: September 2020

Purpose
This paper aims to explore how Sharīʿah-compliant instruments can be used to protect investments and attract investors to Islamic venture capital (IVC). Equity investments in Islamic finance are trailing behind their potential value. This is partly due to the limited instruments available to protect investors, as most of the tools used in conventional venture capital (VC) are deemed Sharīʿah non-compliant.

Design/methodology/approach
The research amends and uses Wright Robbie’s (1998) VC structure and how it can be used to finance small and medium-sized enterprises (SMEs). The study uses secondary data reported in the literature and the expertise of the Sharīʿah scholarship.

Findings
There are Sharīʿah-compliant instruments available for IVC that can be used to protect investments and incentivize potential investors to promote investments in SMEs. At the various stages of the IVC process, preference shares, perpetual mudharabah, diminishing musharakah, musharakah with murabahah, musharakah with qard, negligence clauses, liquidation preference, warrants and supermajority clauses can all be used with appropriate conditions to protect investors and offer incentives for them to invest in IVC.

Practical implications
The research provides a method for screening and evaluating potential deals for SMEs using an amended VC called an IVC scheme with a focus on Sharīʿah-compliant investment protection instruments. The method can promote SMEs and entrepreneurship and financial inclusion for Sharīʿah-compliant investors.

Originality/value
This study contributes new ideas to how IVC can be structured, taking into consideration Sharīʿah constraints. The paper addresses investors’ protection and incentives to attract Sharīʿah-compliant investors, which have been lacking in the literature.