bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination of High Dose Rate Radiations (10X FFF/2400 MU/min/10 MV X-rays) and Paclitaxel Selectively Eliminates Melanoma Cells
Authors: Lodhi Niraj , Sarojini Sreeja , Keck Michaela , Nagpal Poonam , Chiu Yuk Ming , Parvez Zeenath , Adrianzen Laura , Suh K. Stephen 
Published: July 2021

AbstractPurposeMelanoma is one of the most aggressive cancer with 1.6% of total cancer deaths in United States. In recent years treatment options for metastatic melanoma have been improved by the FDA approval of new therapeutic agents. However, these inhibitors based therapies are non-specific and have severe toxicities including hyperkeratosis, photosensitivity, hepatitis, arthralgia and fatigue. The aim of this study is to determine the synthetic lethal effect (paclitaxel and radiations) on melanoma cells and reduce the total radiation doses by increasing the dose rates up to 2400 MU/min.MethodsWe previously reported a radiation treatment (10 MV x-rays, 10X-FFF, dose rate 2400MU/min, low total dose 0.5 Gy) that kills melanoma cells with 80% survival of normal HEM in vitro. In this study we extended the radiation cycle up to four and include paclitaxel treatment to study the synthetic lethal effect on melanoma and two additional normal primary cells, HDF and HEK. Cells were treated with paclitaxel prior to radiations of dose rate of 400 and 2400 MU/min with total radiation dose of only 0.5 Gy. To study induction of apoptosis and cell death, mitochondria respiration assay, DNA damage assay and colony formation assay were performed.ResultsFour days of consequent radiation treatment with paclitaxel significantly reduces the survival of melanoma cells by inducing of apoptosis and mitochondrial damages. After treatment, excessive DNA damage in melanoma cells leads to increase in expression of pro-apoptotic genes (Casp3) and decrease in expression of DNA repair gene (PARP1) and anti-apoptotic gene (Bcl2) to activate apoptosis pathway. Combination of paclitaxel and radiations reduces the survival of melanoma cells colonies when compared to radiation alone.ConclusionOur study indicates radiations with paclitaxel has potential synthetic lethal effect on melanoma cells and can be develop as therapy for melanoma without having toxicities or harmful effects to normal primary skin cells.
Not all smokers are alike: The hidden cost of sustained attention during nicotine abstinence
Authors: Deshpande Harshawardhan U. , Fedota John R. , Castillo Juan , Salmeron Betty Jo , Ross Thomas J. , Stein Elliot A. 
Published: July 2021

AbstractBackgroundNicotine Withdrawal Syndrome (NWS)-associated cognitive deficits are heterogeneous, suggesting underlying endophenotypic subgroups. We identified smoker subgroups based on response accuracy during a cognitively demanding Parametric Flanker Task (PFT) and characterized their distinct neuroimaging endophenotypes using a nicotine state manipulation (sated, abstinent).MethodsForty-five smokers completed the 25-min PFT in two fMRI sessions (nicotine sated, abstinent). Task-evoked NWS-associated errors of omission (EOm), brain activity, underlying functional connectivity (FC), and brain-behavior correlations between subgroups were assessed.ResultsBased on their response accuracy in the high demand PFT condition, smokers split into high (HTP, n=21) and low task performer (LTP, n=24) subgroups. Behaviorally, HTPs showed greater response accuracy independent of nicotine state and greater vulnerability to abstinence-induced EOm. HTPs showed greater BOLD responses in attentional control brain regions for the [correct responses (–) errors of commission] PFT contrast across states. A whole-brain FC analysis with these subgroup-derived regions as seeds revealed two circuits: L Precentral : R Insula and L Insula : R Occipital, with abstinence-induced FC strength increases only in HTPs. Finally, abstinence-induced brain (FC) and behavior (EOm) differences were positively correlated for HTPs in a L Precentral : R Orbitofrontal cortical circuit.ConclusionWe used a cognitive stressor (PFT) to fractionate smokers into two subgroups (HTP/LTP). Only the HTPs demonstrated sustained attention deficits during nicotine abstinence, a stressor in dependent smokers. Unpacking underlying smoker heterogeneity with this ‘dual stressor’ approach revealed distinct smoker subgroups with differential attention deficit responses to withdrawal that could be novel targets for therapeutic interventions to improve cessation outcomes.
A Highly Potent SARS-CoV-2 Blocking Lectin Protein
Authors: Ahan Recep Erdem , Hanifehnezhad Alireza , Şahin Kehribar Ebru , Oguzoglu Tuba Cigdem , Földes Katalin , Özçelik Cemile Elif , Filazi Nazlican , Öztop Sıdıka , Önder Sevgen , Bozkurt Eray Ulaş , Ergünay Koray , Özkul Aykut , Şafak Şeker Urartu Özgür 
Published: July 2021

ABSTRACTCOVID-19 pandemic effected more than 180 million people around the globe causing more than four million deaths as of July 2021. Sars-CoV-2, the new coronavirus, has been identified as the primary cause of the infection. The number of vaccinated people is increasing however prophylactic drugs are highly demanded to ensure a secure social contact. There have been a number of drug molecules repurposed to fight against Sars-CoV-2, however the proofs for the effectiveness of these drug candidates is limited. Here we demonstrated griffithsin (GRFT), a lectin protein, to block the entry of the Sars-CoV2 into the Vero6 cell lines and IFNAR-/-mouse models by attaching to spike protein of the Sars-CoV-2. Given the current mutation frequency of the Sars-CoV-2 we believe that GRFT protein-based drugs will have a high impact in preventing the transmission both on Wuhan strain as well as any other emerging variants including delta variant causing high speed spread of COVID-19.
Methylartist: Tools for Visualising Modified Bases from Nanopore Sequence Data
Authors: Cheetham Seth W. , Kindlova Michaela , Ewing Adam D. 
Published: July 2021

AbstractMethylartist is a consolidated suite of tools for processing, visualising, and analysing nanopore methylation data derived from modified basecalling methods. All detectable methylation types (e.g. 5mCpG, 5hmC, 6mA) are supported, enabling integrated study of base pairs when modified naturally or as part of an experimental protocol.BackgroundCovalent modification of nucleobases is an important component of genomic regulatory regimes across all domains of life [1–3] and is harnessed by various genomic footprinting assays, including DamID[4], SMAC-seq[5], and NOMe-seq[6]. Nanopore sequencing offers comprehensive assessment of base modifications from arbitrarily long sequence reads through analysis of electrical current profiles, generally through machine learning models trained to discriminate between modified and unmodified bases [7]. An increasing number of computational tools have been developed or enhanced for calling modified bases [8], including nanopolish [7], megalodon [9], and guppy [10], along with an increasing number of available pre-trained models.
Pectin remodeling belongs to a homeostatic system and triggers transcriptomic and hormonal modulations
Authors: Jobert François , Guénin Stéphanie , Voxeur Aline , Lee Kieran J. D. , Bouton Sophie , Sénéchal Fabien , Hocq Ludivine , Mongelard Gaëlle , Demailly Hervé , Amakorová Petra , Strnad Miroslav , Vernhettes Samantha , Mouille Gregory , Pilard Serge , Knox J. Paul , Novák Ondřej , Pelloux Jérôme , Gutierrez Laurent 
Published: July 2021

SUMMARYHere, we focused on the biological modifications arisen from a strong and transient variation of the pectin methylesterification status during the seed-to-seedling transition.A reverse genetic approach was used to trigger specific reduction of pectin de-methylesterification during the seed maturation stage and the related physiological effects were assessed using a combination of biochemical, transcriptomic and microscopic analyses.Arabidopsis PME36 is required to implement the characteristic pattern of de-methylesterified pectin in the mature seed. While this pattern is strongly impaired in pme36-1 and pme36-2 mature seed, no phenotypical effect is observed in the knockout mutant during seed germination. By analyzing hormone homeostasis and gene expression regulation, we show a strong and dynamic physiological disorder in the mutant, which reveals the existence of a complex compensatory mechanism overcoming the defect in pectin de-methylesterification.Our results reveal that pectin methylesterification status acts as upstream modulator involved in an undescribed homeostatic system in which pectin remodeling, hormone signaling and transcriptomic regulations interact to ensure the maintenance of a normal seed-to-seedling developmental program.
A Combination Strategy of Solubility Enhancers for Effective Production of Soluble and Bioactive Human Enterokinase
Authors: Kwon Jinhak , Cho Hyeongjun , Kim Seungmin , Ryu Yiseul , Lee Joong-jae 
Published: July 2021

AbstractEnterokinase is one of the hydrolases that catalyze hydrolysis to regulate biological processes in intestinal visceral mucosa. Enterokinase plays an essential role in accelerating the process of protein digestion as it converts trypsinogen into active trypsin by accurately recognizing and cleaving a specific peptide sequence, (Asp)4-Lys. Due to its exceptional substrate specificity, enterokinase is widely used as a versatile molecular tool in various bioprocessing, especially in removing fusion tags from recombinant proteins. Despite its biotechnological importance, mass production of soluble enterokinase in bacteria still remains an unsolved challenge. Here, we present an effective production strategy of human enterokinase using tandemly linked solubility enhancers consisting of thioredoxin, phosphoglycerate kinase or maltose-binding protein. The resulting enterokinases exhibited significantly enhanced solubility and bacterial expression level while retaining enzymatic activity, which demonstrates that combinatorial design of fusion proteins has the potential to provide an efficient way to produce recombinant proteins in bacteria.
High-speed imaging of light-induced photoreceptor microsaccades in compound eyes
Authors: Kemppainen Joni , Mansour Neveen , Takalo Jouni , Juusola Mikko 
Published: July 2021

AbstractInside compound eyes, photoreceptors contract to light changes, sharpening retinal images of the moving world in time. Current methods to measure these so-called photoreceptor microsaccades in living insects are spatially limited and technically challenging. Here, we present goniometric high-speed deep pseudopupil (GHS-DPP) microscopy to assess how the rhabdomeric insect photoreceptors and their microsaccades are organised across the compound eyes. This method enables non-invasive rhabdomere orientation mapping, whilst their microsaccades can be locally light-activated, revealing the eyes’ underlying active sampling motifs. By comparing the microsaccades in wild-typeDrosophila’s open rhabdom eyes tospam-mutant eyes, reverted to an ancestral fused rhabdom state, and honeybee’s fused rhabdom eyes, we show how different eye types sample light information. These results show different ways compound eyes initiate the conversion of spatial light patterns in the environment into temporal neural signals and highlight how this active sampling can evolve with insects’ visual needs.
Memories in a network with excitatory and inhibitory plasticity are encoded in the spiking irregularity
Authors: Gallinaro Júlia V. , Clopath Claudia 
Published: July 2021

AbstractCell assemblies are thought to be the substrate of memory in the brain. Theoretical studies have previously shown that assemblies can be formed in networks with multiple types of plasticity. But how exactly they are formed and how they encode information is yet to be fully understood. One possibility is that memories are stored in silent assemblies. Here we used a computational model to study the formation of silent assemblies in a network of spiking neurons with excitatory and inhibitory plasticity. We found that even though the formed assemblies were silent in terms of mean firing rate, they had an increased coefficient of variation of inter-spike intervals. We also found that this spiking irregularity could be readout with support of short-term plasticity, and that it could contribute to the longevity of memories.
Non-specific adhesive forces between filaments and membraneless organelles
Authors: Böddeker Thomas J. , Rosowski Kathryn A. , Berchtold Doris , Emmanouilidis Leonidas , Han Yaning , Allain Frédéric H. T. , Style Robert W. , Pelkmans Lucas , Dufresne Eric R. 
Published: July 2021

AbstractMembraneless organelles are liquid-like domains that form inside living cells by phase-separation. While standard physical models of their formation assume their surroundings to be a simple liquid, the cytoplasm is an active viscoelastic environment. To investigate potential coupling of phase separation with the cytoskeleton, we quantify structural correlations of stress granules and microtubules in a human-derived epithelial cell line. We find that microtubule networks are significantly perturbed in the vicinity of stress granules, and that large stress granules conform to the local pore-structure of the microtubule network. When microtubules are depolymerized by nocodazole, tubulin enrichment is localized near the surface of stress granules. We interpret these data using a thermodynamic model of partitioning of particles to the surface and bulk of droplets. This analysis shows that proteins generically have a non-specific affinity for droplet interfaces, which becomes most apparent when they weakly partition to the bulk of droplets and have a large molecular weight. In this framework, our data is consistent with a weak (≲ kbT) affinity of tubulin sub-units for stress granule interfaces. As microtubules polymerize their affinity for interfaces increases, providing sufficient adhesion to deform droplets and/or the network. We validate this basic physical phenomena in vitro through the interaction of a simple protein-RNA condensate with tubulin and microtubules.
Copy number variations with adaptive potential in caribou (Rangifer tarandus): genome architecture and new annotated genome assembly
Authors: Prunier Julien , Carrier Alexandra , Gilbert Isabelle , Poisson William , Albert Vicky , Taillon Joëlle , Bourret Vincent , Côté Steeve D. , Droit Arnaud , Robert Claude 
Published: July 2021

AbstractBackgroundRangifer tarandus (caribou and reindeer) has experienced recent drastic population size reductions throughout its circumpolar distribution. In efforts aimed at preserving caribou in North America and reindeer in Eurasia, genetic diversity conservation is of utmost importance, particularly the adaptive genetic diversity. To facilitate genomic studies of the caribou population, we improved genome assembly and annotation by combining long-read, linked-read and RNA sequencing technologies. As copy number variations (CNVs) are known to impact phenotype and are therefore likely to play a key role in adaptation, we investigated CNVs among the genomes of individuals representing three ecotypes of caribou (migratory, boreal and mountain).ResultsUsing de novo transcriptome assembly and similarity with annotated human gene sequences, we identified 17,394 robust gene models embedded in a new highly contiguous genome assembly made of 13,994 scaffolds and presenting the highest N50 reported to date. A BUSCO analysis supported the high accuracy of this assembly, 90% of which being represented by only 131 scaffolds. Genome level comparisons with domestic ruminant species showed high synteny within this clade. A total of 1,698 large CNVs (length > 1kb) were identified, including 332 overlapping coding sequences annotated for functions related to immunity, musculoskeletal development or metabolism regulation and others. While the CNV distribution over the genome revealed 31 CNV hotspots, 43 large CNVs were particularly distinctive of the migratory and sedentary ecotypes and included genes annotated for functions related to cardiac development, fatty acid regulation, cold responses, locomotory behavior or environmental perception (hearing and sight), that can be related to the expected adaptations.ConclusionsThis work includes the first publicly available annotation of the Rangifer tarandus genome and the first genome assembly allowing genome architecture analyses. This robust annotation based on truly expressed sequences showed a distribution overlapping many CNVs that are promising candidates given the annotations supporting their involvement in adaptation. This new highly contiguous assembly will allow relative localization of genetic variations and features and will be a valuable resource for molecular tool development and genomic studies aimed at describing and preserving this species.
AD Informer Set: Chemical tools to facilitate Alzheimer’s disease drug discovery
Authors: Potjewyd Frances M. , Annor-Gyamfi Joel K. , Aubé Jeffrey , Chu Shaoyou , Conlon Ivie L. , Frankowski Kevin J. , Guduru Shiva K. R. , Hardy Brian P. , Hopkins Megan D. , Kinoshita Chizuru , Kireev Dmitri B. , Mason Emily R. , Moerk Charles Travis , Nwogbo Felix , Pearce Kenneth H. , Richardson Timothy , Rogers David A. , Soni Disha M. , Stashko Michael , Wang Xiaodong , Wells Carrow , Willson Timothy M. , Frye Stephen V. , Young Jessica E. , Axtman Alison D. 
Published: July 2021

ABSTRACTIntroductionThe portfolio of novel targets to treat Alzheimer’s disease (AD) has been enriched by the AMP-AD program.MethodsA cheminformatics-driven effort enabled identification of existing small molecule modulators for many protein targets nominated by AMP-AD and suitable positive control compounds to be included in the set.ResultsWe have built an annotated set of 171 small molecule modulators, including mostly inhibitors, targeting 98 unique proteins that have been nominated by AMP-AD consortium members as novel targets for AD treatment. These small molecules vary in their quality and should be considered chemical tools that can be used in efforts to validate therapeutic hypotheses, but which would require further optimization. A physical copy of the AD Informer Set can be ordered via the AD Knowledge Portal.DiscussionSmall molecule tools that enable target validation are important tools for the translation of novel hypotheses into viable therapeutic strategies for AD.
Faces of men with high serum testosterone are less attractive for women during the fertility phase of the menstrual cycle
Authors: Krejza Jaroslaw , Sledziewski Rafal , Tabedzki Marek , Chen Rong , Krzystanek Ewa , Arkuszewski Michal , Odachowska Magdalena , Kwiatkowska Kinga , Marynowska Marcelina , Rogowski Maciej , Ustymowicz Andrzej 
Published: July 2021

AbstractThe attractiveness of the human face plays an essential role in mating as it may signal the genetic suitability of a mate. The controversial ‘ovulatory shift hypothesis’ postulates that women in the fertile phase of the menstrual cycle would prefer faces of masculine men with high testosterone that signals ‘good genes’, whereas in the non-fertile phase they prefer traits signaling the willingness to provide parental care. To examine relationships between men’s testosterone and women’s preferences for men’s faces on day 13 of the menstrual cycle, 19 young women rated the attractiveness of images of the natural faces of 77 young men. Using advanced Bayesian multilevel modeling we showed that the attractiveness of men’s faces is significantly lower in men with a high concentration of serum total testosterone, even taking into account the concentration of serum estrogen in the raters. The average men’s face composited from images of 39 faces rated above pool median attractiveness rate, was slightly narrower than the average face composited from 38 less attractive faces. Our results challenge the ‘ovulatory shift hypothesis’ as faces of males with high circulating testosterone were rated as less attractive than faces of males with lower testosterone by women on the fertile phase of the cycle.
Integrative proteomics and phosphoproteomics reveals phosphorylation networks involved in the maintenance and expression of embryogenic competence in sugarcane callus
Authors: Xavier Lucas R. , Almeida Felipe A. , Pinto Vitor B. , Passamani Lucas Z , Santa-Catarina Claudete , Filho Gonçalo A. de S. , Mooney Brian P. , Thelen Jay J. , Silveira Vanildo 
Published: July 2021

ABSTRACTSugarcane (Saccharum spp.) is one of the most important crops for sugar, biofuel, and bioenergy production and has become an important commodity in the worldwide agricultural market in more than 100 countries. In this study, label-free quantitative proteomics and phosphoproteomics analyses were performed to investigate signaling events related to somatic embryo maturation and differentiation in sugarcane. Embryogenic callus (EC) at multiplication (EC0) and after 14 days (EC14) of maturation were compared. The EC14/EC0 comparison found that 251 phosphoproteins and 700 proteins were differentially regulated and accumulated, respectively. Metabolic pathway analysis showed that these proteins and phosphoproteins were enriched in lysine degradation and starch/sucrose metabolism during multiplication, whereas the differentiation of somatic embryos was found to involve the regulation of energetic metabolism, including the TCA cycle, oxidative phosphorylation, and carbon metabolism. Multiplication-related phosphoproteins were mainly associated with abscisic acid responses and transcriptional regulation of the TOPLESS (TPL), SNF1 kinase homolog 10 (KIN10), SEUSS (SEU), and LEUNIG_HOMOLOG (LUH) proteins. Among the maturation-related phosphoproteins, the phosphorylation of light harvesting complex photosystem ii, CURVATURE THYLAKOID 1B, vacuolar proton ATPase A1 and phytochrome interacting factor 3-LIKE 5 was found to be associated with bioenergetic metabolism and carbon fixation. A motif analysis revealed 15 phosphorylation motifs, and among these, the [D-pS/T-x-D] motif was unique among the phosphopeptides identified during somatic embryo differentiation. A coexpression network analysis of proteins and phosphoproteins revealed interactions among SNF1-related protein kinase 2 (SnRK2), abscisic acid responsive elements-binding factor 2 (ABF2), and KIN10, which indicated the role of these proteins in embryogenic competence in EC0. The interactions among ubiquitin-conjugating enzyme 5, ubiquitin-conjugating enzyme 35, small ubiquitin-like modifier 1, and histone deacetylase 1 may be involved in posttranslational protein modification during embryo maturation. Argonaute 1 (AGO1) also interacts with POLTERGEIST (POL) and may integrate gene silencing with the regulation of meristem identity during somatic embryo development. These results reveal novel dynamics of protein regulation in somatic embryogenesis and identify new potential players in somatic embryo differentiation and their phosphosites.