bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mapping epigenetic divergence in the massive radiation of Lake Malawi cichlid fishes
Authors: Vernaz Grégoire , Malinsky Milan , Svardal Hannes , Du Mingliu , Tyers Alexandra M. , Santos M. Emília , Durbin Richard , Genner Martin J. , Turner George F. , Miska Eric A. 
Published: November 2020

ABSTRACTEpigenetic variation modulates gene expression and can be heritable. However, knowledge of the contribution of epigenetic divergence to adaptive diversification in nature remains limited. The massive evolutionary radiation of Lake Malawi cichlid fishes displaying extensive phenotypic diversity despite extremely low sequence divergence is an excellent system to study the epigenomic contribution to adaptation. Here, we present a comparative genome-wide methylome and transcriptome study, focussing on liver and muscle tissues in phenotypically divergent cichlid species. In both tissues we find substantial methylome divergence among species. Differentially methylated regions (DMR), enriched in evolutionary young transposons, are associated with transcription changes of ecologically-relevant genes related to energy expenditure and lipid metabolism, pointing to a link between dietary ecology and methylome divergence. Unexpectedly, half of all species-specific DMRs are shared across tissues and are enriched in developmental genes, likely reflecting distinct epigenetic developmental programmes. Our study reveals substantial methylome divergence in closely-related cichlid fishes and represents a resource to study the role of epigenetics in species diversification.
Double Lock of a Potent Human Monoclonal Antibody against SARS-CoV-2
Authors: Zhu Ling , Deng Yong-Qiang , Zhang Rong-Rong , Cui Zhen , Sun Chun-Yun , Fan Chang-Fa , Xing Xiaorui , Huang Weijin , Chen Qi , Zhang Na-Na , Ye Qing , Cao Tian-Shu , Wang Nan , Wang Lei , Cao Lei , Wang Huiyu , Kong Desheng , Ma Juan , Luo Chunxia , Zhang Yanjing , Nie Jianhui , Sun Yao , Lv Zhe , Shaw Neil , Li Qianqian , Li Xiao-Feng , Hu Junjie , Xie Liangzhi , Rao Zihe , Wang Youchun , Wang Xiangxi , Qin Cheng-Feng 
Published: November 2020

SummaryReceptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10-fold of effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the RBD, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.HighlightsSARS-CoV-2 specific antibody, HB27, blocks viral receptor binding and membrane fusionHB27 confers prophylactic and therapeutic protection against SARS-CoV-2 in mice modelsRhesus macaques showed no adverse side effects when administered with HB27Cryo-EM studies suggest that HB27 sterically occludes SARS-CoV-2 from its receptor
Rif1 regulates telomere length through conserved HEAT repeats
Authors: Shubin Calla B , Mayangsari Rini , Swett Ariel D , Greider Carol W 
Published: November 2020

ABSTRACTIn budding yeast, Rif1 negatively regulates telomere length, but the mechanism of this regulation has remained elusive. Previous work identified several functional domains of Rif1, but none of these has been shown to mediate telomere length. To define Rif1 domains responsible for telomere regulation, we localized truncations of Rif1 to a single specific telomere and measured telomere length of that telomere compared to bulk telomeres. We found that a domain in the N-terminus containing HEAT repeats, Rif1177-996, was sufficient for length regulation when tethered to the telomere. Charged residues in this region were previously proposed to mediate DNA binding. We found that mutation of these residues disrupted telomere length regulation even when Rif1 was tethered to the telomere. Mutation of other conserved residues in this region, which were not predicted to interact with DNA, also disrupted telomere length maintenance, while mutation of conserved residues distal to this region did not. Our data suggests that conserved amino acids in the region from 436 to 577 play a functional role in telomere length regulation, which is separate from their proposed DNA-binding function. We propose that the Rif1 HEAT repeats region represents a protein-protein binding interface that mediates telomere length regulation.
The Cholesteryl Ester Transfer Protein (CETP) raises Cholesterol Levels in the Brain and affects Presenilin-mediated Gene Regulation
Authors: Oestereich Felix , Yousefpour Noosha , Yang Ethan , Ribeiro-da-Silva Alfredo , Chaurand Pierre , Munter Lisa Marie 
Published: November 2020

AbstractThe cholesteryl ester transfer protein (CETP) is a lipid transfer protein responsible for the exchange of cholesteryl esters and triglycerides between lipoproteins. Decreased CETP activity is associated with longevity, cardiovascular health, and maintenance of good cognitive performance. Interestingly, mice lack the CETP-encoding gene and have very low levels of low-density lipoprotein (LDL) particles compared to humans. To understand how CETP activity affects the brain, we utilised CETP transgenic (CETPtg) mice showing elevated LDL levels on a high cholesterol diet inducing CETP expression. We found that CETPtg mice had up to 25% higher cholesterol levels in the brain. Using a microarray on astrocyte-derived mRNA, we found that this cholesterol increase is likely not due to astrocytic-dependentde novosynthesis of cholesterol. Rather, several genes linked to Alzheimer’s disease were altered in CETPtg mice. Most interestingly, we found activation of the G-protein coupled receptor EP4 and γ-secretase as upstream regulators of these transcriptional changes. Furtherin vitrostudies showed that CETP expression was sufficient to activate γ-secretase activity. The data suggest that CETP activity affects brain’s health through modulating cholesterol levels and Alzheimer’s-related pathways. Therefore, CETPtg mice constitute a valuable research tool to investigate the impact of the cholesterol metabolism on brain functions.
Robust expression of LINE-1 retrotransposon encoded proteins in oral squamous cell carcinoma
Authors: Mukherjee Koel , Sur Debpali , Singh Abhijeet , Rai Sandhya , Das Neeladrisingha , Narindi Srinu , Sekar Rakshanya , Dhingra Vandana Kumar , Jat Bhinyaram , Balraam K V Vinu , Agarwal Satya Prakash , Mandal Prabhat Kumar 
Published: November 2020

AbstractRetrotransposons are sequences which transpose within genomes using RNA as an intermediate. Long INterpersed Element-1 (LINE1 or L1) is the only active retrotransposon occupying around 17% of the human genome with an estimated 500,000 copies. An active L1 encodes two proteins (L1ORF1p and L1ORF2p); both of which are critical in the process of retrotransposition. In-order to propagate to the nextgeneration, L1s remain active in germ tissues and at an early stage of development. Surprisingly, by some unknown mechanism, L1 also shows activity in certain parts of the normal brain and many cancers. L1 activity is generally determined by assaying L1ORF1p because of its high expression and availability of the antibody. However, due to its lowerexpression and the unavailability of a robust antibody, detection of L1ORF2p has been limited. L1ORF2p is the crucial protein in the process of retrotransposition as it provides endonuclease and reverse transcriptase (RT) activity. Here, we report a novel human L1ORF2p antibody generated using an 80-amino-acid stretch from the RT domain, which is highly conserved among different species. The antibody detects significant L1ORF2p expression in murine germ tissues and human oral squamous cell carcinoma (OSCC) samples. This particular cancer is prevalent in India due to excessive use of tobacco. Here, using our in-house antibodies against L1 proteins, we show that more than fifty percent of samples are positive for L1 proteins. Overall, we reported a novel L1ORF2p antibody that detects L1 activity in germ tissues and OSCC
Cassette recruitment in the chromosomal Integron ofVibrio cholerae
Authors: Vit Claire , Richard Egill , Fournes Florian , Whiteway Clémence , Eyer Xavier , Lapaillerie Delphine , Parissi Vincent , Mazel Didier , Loot Céline 
Published: November 2020

AbstractIntegrons are genetic systems conferring to bacteria a rapid adaptation capability. The integron integrase is able to capture, stockpile and shuffle novel functions embedded in cassettes. This involves the recognition of both substrates, theattIsite, and the cassette associatedattCsites. Integrons can be sedentary and chromosomally located (SCI) or, carried by conjugative plasmids (Mobile Integron, MI), hence favoring their dissemination among bacteria. Here, for the first time, we investigate the cassette recruitment in theVibrio choleraeSCI during conjugation and natural transformation. We demonstrated that horizontally transferred cassette can be recruited inside the chromosomal integron. The endogenous integrase expression is sufficiently triggered, after SOS response induction mediated by the entry of single-stranded cassettes during conjugation and natural transformation, to mediate significant cassette insertion. We demonstrate that theattIAinsertion is preferential, despite the presence of 180attCsites in the integron array. Thanks to the presence of a promoter in theattIAsite vicinity, all these newly inserted cassettes are expressed and prone to adaptive selection. We also show that the RecA protein is critical for cassette recruitment inV. choleraeSCI but not in MIs. Moreover,a contrarioto MIs, theV. choleraeSCI is not active in others bacterial hosts. MIs might have evolved from the SCIs by overcoming host factors, which would explain their large dissemination in bacteria and their role in the antibioresistance expansion.
Specific quorum sensing molecules are possibly associated with responses to herbicide toxicity in aPseudomonasstrain
Authors: Nunes de Freitas Paloma Nathane , Flávia da Silva Rovida Amanda , Silva Caroline Rosa , Pileggi Sônia Alvim Veiga , Olchanheski Luiz Ricardo , Pileggi Marcos 
Published: November 2020

AbstractPesticides contribute to pest control and increased agricultural production; however, they are toxic to non-target organisms and they contaminate the environment. The exposure of bacteria to these substances can lead to the need for physiological and structural changes for survival, which can be determined by genes whose expression is regulated by quorum sensing (QS). However, it is not yet clear whether these processes can be induced by herbicides. Thus, the aim of this work was to determine whether there is a QS response system in aPseudomonas fluorescensstrain that is modulated by herbicides. This strain was isolated from water storage tanks used for washing pesticide packaging and was tested against herbicides containing saflufenacil, glyphosate, sulfentrazone, 2,4-D, and dicamba as active molecules. We found that this strain possibly uses QS signaling molecules to control the production of reactive oxygen species, whether those produced by the bacterium’s energy generating system or by molecules induced by the presence of saflufenacil and glyphosate. This strain used other signaling molecules for various stages of biofilm formation in the presence of herbicides containing sulfentrazone, 2,4-D, and dicamba. These findings, as an initial screening which will guide new studies, suggest that this strain has a flexibility in gene expression that allows survival in the presence of several stress-inducing molecules, regardless of previous exposure. This represents a model of metabolic and physiological plasticity. Biofilms made up of several bacterial species can use this model in agricultural environments, increasing the potential for degradation of xenobiotics, but with impacts on diversity and functionality of microbiotas in these environments.
Varying trypsin inhibitor activity in differently processed soybean expellers linearly reduces prececal amino acid digestibility in broilers
Authors: Kuenz S. , Thurner S. , Hoffmann D. , Kraft K. , Wiltafsky-Martin M. , Damme K. , Windisch W. , Brugger D. 
Published: November 2020

AbstractThe present study investigated the effect of varying trypsin inhibitor activity (TIA) in differently processed soybean expellers on apparent prececal amino acid (AA) digestibility in male broiler chickens. Two different raw soybean batches were treated using four different processing techniques (thermal, hydrothermal, pressure, kilning) at varying intensities. In this way, 45 expeller extracted soybean meal (ESBM) variants were created. The processed soybean variants were then merged into a basal diet (160 g/kg crude protein (CP)) at two inclusion levels (15%, 30%) resulting in 91 different diets (1 basal diet plus 90 experimental diets) with TIA ranging from 0.4 mg/g to 8.5 mg/g. All diets contained 0.5% of titanium dioxide (TiO2). During four experimental runs, a total of 5,460 1-day old male broiler chickens (Ross 308) were fed a commercial starter diet (CP 215 g/kg, 14 g/kg Lysine, 12.5 MJ ME/kg) ad libitum from day 1 to day 14. Subsequently, birds were allocated to a total of 546 pens with 10 birds per pen and were fed the 91 experimental dietsad libitum. At day 22, birds were sacrificed and digesta of the terminal ileum was collected for determination of AA digestibility. TIA depressed the prececal digestibility of every single AA significantly in a straight linear fashion (p < 0.001). cystine and methionine expressed the strongest suppression by TIA with cystine showing the lowest apparent prececal digestibility measured (4.94% at 23.6 mg/g TIA in raw ESBM). Correspondingly, live weight (LW) (p < 0.001) and total weight gain (TWG) (p < 0.001) declined in a linear manner with increasing TIA in feed. The present data demonstrate that TIA severely depresses digestibility of essential and non-essential AA and thus growth performance in a straight linear fashion. On the one hand, this questions the usefulness of defined upper limits of TIA in soy products whereas on the other hand, TIA must be considered when testing raw components for their feed protein value in vivo.
eNOS-induced vascular barrier disruption in retinopathy by c-Src activation and tyrosine phosphorylation of VE-cadherin
Authors: Ninchoji Takeshi , Love Dominic T. , Smith Ross O. , Hedlund Marie , Vestweber Dietmar , Sessa William C. , Claesson-Welsh Lena 
Published: November 2020

AbstractHypoxia and the production of vascular endothelial growth factor A (VEGFA) promote blood vessel leakiness and edema in ocular diseases. Therapeutics targeting VEGFA suppress leakiness and edema but aggravate hypoxia; therefore, new therapeutics are needed. We examined the role of endothelial nitric oxide synthase (eNOS) in pathological neovascularization and vessel permeability during oxygen-induced retinopathy. NO formation was suppressed chemically using L-NMMA, or genetically, in eNOS serine to alanine (S1176A) mutant mice, resulting in reduced retinal neoangiogenesis. Both strategies resulted in reduced vascular leakage by stabilizing endothelial adherens junctions through suppressed phosphorylation of vascular endothelial (VE)-cadherin Y685 in a c-Src-dependent manner. Intervention treatment by a single dose of L-NMMA in established retinopathy restored the vascular barrier and prevented leakage. We conclude that eNOS induces destabilization of adherens junctions and vascular hyperpermeability by converging with the VEGFA/VEGFR2/c-Src/VE-cadherin pathway and that this pathway can be selectively inhibited by blocking NO formation.
Spatial control of gene expression in flies using bacterially derived binary transactivation systems
Authors: Gamez Stephanie , Vesga Luis C. , Mendez-Sanchez Stelia C. , Akbari Omar S. 
Published: November 2020

AbstractControlling gene expression is an instrumental tool for biotechnology, as it enables the dissection of gene function, affording precise spatial-temporal resolution. To generate this control, binary transactivational systems have been used employing a modular activator consisting of a DNA binding domain(s) fused to activation domain(s). For fly genetics, many binary transactivational systems have been exploitedin vivo; however as the study of complex problems often requires multiple systems that can be used in parallel, there is a need to identify additional bipartite genetic systems. To expand this molecular genetic toolbox, we tested multiple bacterially-derived binary transactivational systems inDrosophila melanogasterincluding thep-CymR operon fromPseudomonas putida, PipR operon fromStreptomyces coelicolor, TtgR operon fromPseudomonas putida, and the VanR operon fromCaulobacter crescentus. Our work provides the first characterization of these systems in an animal modelin vivo. For each system we demonstrate robust tissue-specific spatial transactivation of reporter gene expression, enabling future studies to exploit these transactivational systems for molecular genetic studies.
Toxoplasma gondiiserine hydrolases regulate parasite lipid mobilization during growth and replication within the host
Authors: Onguka Ouma , Babin Brett M. , Lakemeyer Markus , Foe Ian T. , Amara Neri , Terrell Stephanie M. , Lum Kenneth M. , Cieplak Piotr , Niphakis Micah J. , Long Jonathan Z. , Bogyo Matthew 
Published: November 2020

SummaryThe intracellular protozoan parasiteToxoplasma gondiimust scavenge cholesterol and other lipids from the host to facilitate intracellular growth and replication. Enzymes responsible for neutral lipid synthesis have been identified but there is no evidence for enzymes that catalyze lipolysis of cholesterol esters and esterified lipids. Here we characterize severalT. gondiiserine hydrolases with esterase and thioesterase activities that were previously thought to be depalmitoylating enzymes. We find they do not cleave palmitoyl thiol esters but rather hydrolyze short chain lipid esters. Deletion of one of the hydrolases results in alterations in levels of multiple lipids species. We also identify small molecule inhibitors of these hydrolases and show that treatment of parasites results in phenotypic defects reminiscent of parasites exposed to excess cholesterol or oleic acid. Together, these data characterize enzymes necessary for processing lipids critical for infection and highlight the potential for targeting parasite hydrolases for therapeutic applications.HighlightsBioinformatic and biochemical characterization ofT. gondiiserine hydrolases reveals substrate preference between enzymes with similar catalytic foldT. gondiiserine hydrolases previously thought to be depalmitoylases are lipid metabolizing enzymesT. gondiilipid metabolism pathways utilize enzymes that are viable therapeutic targets
Crystal structure of barley agmatine coumaroyltransferase, an N-acyltransferase from the BAHD superfamily
Authors: Yamane Miyo , Takenoya Mihoko , Yajima Shunsuke , Sue Masayuki 
Published: November 2020

The enzymes of the BAHD superfamily, a large group of acyl-CoA-dependent acyltransferases in plants, are involved in the biosynthesis of diverse secondary metabolites. While the structures of several O-acyltransferases from the BAHD superfamily, such as hydroxycinnamoyl-CoA shikimate hydroxycinnamoyl transferase, have been elucidated, no structural information on N-acyltransferases is available. Hordeum vulgare agmatine coumaroyltransferase (HvACT) is an N-acyltransferase from the BAHD superfamily and is one of the most important enzymes in the secondary metabolism of barley. Here, an apo-form structure of HvACT is reported as the first structure of an N-acyltransferase from the BAHD superfamily. HvACT crystals diffracted to 1.8 Å resolution and belonged to the monoclinic space group P21, with unit-cell parameters a = 57.6, b = 59.5, c = 73.6 Å, α = 90, β = 91.3 , γ = 90°. Like other known BAHD superfamily structures, HvACT contains two domains that adopt a two-layer αβ-sandwich architecture and a solvent-exposed channel that penetrates the enzyme core.
Financial statement comparability and takeover efficiency: a pitch
Authors: Duong Lien , Truong Thu Phuong 
Published: November 2020

Purpose
This paper aims to adopt the pitching research template of Professor Robert Faff for a proposed research project on financial statement comparability and takeover efficiency.

Design/methodology/approach
This paper starts with a brief background on using the pitch research template of Professor Robert Faff pitching methodology for core elements of the research project. Then, the authors’ personal reflections on the pitch exercise are discussed.

Findings
It is found that the template is helpful in articulating and refining the research ideas among co-authors. It is an excellent way to communicate the research ideas to the panel of editors.

Originality/value
The pitching template is an effective tool for mid-career researchers to position their research ideas in the literature.
Generalist, specialist and generic positions experienced by occupational therapists in Norwegian municipalities
Authors: Horghagen Sissel , Bonsaksen Tore , Sveen Unni , Dolva Anne Stine , Arntzen Cathrine 
Published: November 2020

Purpose
Reforms in the health-care system may impact how health-care professionals perceive and enact their roles. This study aims to examine the way in which occupational therapists experience and describe their roles in municipalities after the implementation of a health reform (the Coordination Act) in Norway.

Design/methodology/approach
This qualitative study was designed within the perspectives of social constructivism. Data was collected through focus group interviews with 10 community-working occupational therapists. A thematic framework analysis was used to examine the participants’ experiences.

Findings
The following four themes emerged: external factors that framed and shaped the occupational therapists’ roles in municipalities; the strengths and dilemmas of the generalist; the problematic generic position and the strengths; and dilemmas of the specialist.

Originality/value
The study suggests that occupational therapy practitioners should identify new opportunities and adapt to health reform changes. They also need to renegotiate their roles as the health reforms require more specialized competences. Greater emphasis must be placed on the core knowledge and competences of occupational therapists to strengthen their professional identity in the municipalities.