bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biofabrication of muscle fibers enhanced with plant viral nanoparticles using surface chaotic flows
Authors: Frías-Sánchez Ada I. , Quevedo-Moreno Diego A. , Samandari Mohamadmahdi , Tavares-Negrete Jorge A. , Sánchez-Rodríguez Víctor Hugo , González-Gamboa Ivonne , Ponz Fernando , Alvarez Mario M. , Trujillo-de Santiago Grissel 
Published: July 2020

AbstractMultiple human tissues exhibit fibrous nature. Therefore, the fabrication of hydrogel filaments for tissue engineering is a trending topic. Current tissue models are made of materials that often require further enhancement for appropriate cell attachment, proliferation and differentiation. Here we present a simple strategy, based on the use surface chaotic flows amenable of mathematical modeling, to fabricate continuous, long and thin filaments of gelatin methacryloyl (GelMA).The fabrication of these filaments is achieved by chaotic advection in a finely controlled and miniaturized version of the journal bearing (JB) system. A drop of GelMA pregel was injected on a higher-density viscous fluid (glycerin) and a chaotic flow is applied through an iterative process. The hydrogel drop is exponentially deformed and elongated to generate a fiber, which was then polymerized under UV-light exposure. Computational fluid dynamic (CFD) simulations are conducted to determine the characteristics of the flow and design the experimental conditions for fabrication of the fibers. GelMA fibers were effectively used as scaffolds for C2C12 myoblast cells. Experimental results demonstrate an accurate accordance with CFD simulations for the predicted length of the fibers.Plant-based viral nanoparticles (i.e.,Turnip mosaic virus; TuMV) were then integrated to the hydrogel fibers as a secondary nano-scaffold for cells for enhanced muscle tissue engineering. The addition of TuMV significantly increased the metabolic activity of the cell-seeded fibers (p*<0.05), strengthened cell attachment throughout the first 28 days, improved cell alignment, and promoted the generation of structures that resemble natural mammal muscle tissues.Chaotic 2D-printing is proven to be a viable method for the fabrication of hydrogel fibers. The combined use of thin and long GelMA hydrogel fibers enhanced with flexuous virions offers a promising alternative for scaffolding of muscle cells and show potential to be used as cost-effective models for muscle tissue engineering purposes.
Comprehensive exploration of the genetic contribution of the dopaminergic and serotonergic pathways to psychiatric disorders
Authors: Cabana-Domínguez Judit , Torrico Bàrbara , Reif Andreas , Fernàndez-Castillo Noèlia , Cormand Bru 
Published: July 2020

ABSTRACTPsychiatric disorders are highly prevalent and display considerable clinical and genetic overlap. Dopaminergic and serotonergic neurotransmission have been shown to have an important role in many psychiatric disorders. Here we aim to assess the genetic contribution of these systems to eight psychiatric disorders (ADHD, ANO, ASD, BIP, MD, OCD, SCZ and TS) using publicly available GWAS analyses performed by the Psychiatric Genomics Consortium. To do so, we elaborated four different gene sets using the Gene Ontology and KEGG pathways tools: two ‘wide’ selections for dopamine (DA) and for serotonin (SERT), and two ‘core’ selections for the same systems. At the gene level, we found 67 genes from the DA and/or SERT gene sets significantly associated with one of the studied disorders, and 12 of them were associated with two different disorders. Gene-set analysis revealed significant associations for ADHD and ASD with the wide DA gene set, for BIP with the wide SERT gene set, and for MD with both the core DA set and the core SERT set. Interestingly, interrogation of the cross-disorder GWAS meta-analysis displayed association with the wide DA gene set. To our knowledge, this is the first time that these two neurotransmitter systems have systematically been inspected in these disorders. Our results support a cross-disorder contribution of dopaminergic and serotonergic systems in several psychiatric conditions.
Public attention and policy responses to COVID-19 pandemic⋆
Authors: Aksoy Cevat Giray , Ganslmeier Michael , Poutvaara Panu 
Published: July 2020

AbstractEarly non-pharmaceutical interventions (NPI) significantly reduced the death toll of the COVID-19 pandemic. Yet, there are vast differences in how quickly governments implemented NPIs. In this paper, we analyze the role of public attention, measured as the share of daily Google searches in a country related to COVID-19, in the timing of the NPI responses. We first show that public attention depends strongly on whether there are cases in own country. We then show that countries with high levels of public attention are more likely to implement non-pharmaceutical interventions, even after controlling for the number of cases and deaths. Finally, we show that the extent to which a government responds to public attention is highly dependent on the country’s institutional quality. The positive effect of public attention on policy implementation is driven entirely by countries with good institutions.
Oncogenic H-Ras Signaling Differentially Targets Replicative and Specialized DNA Polymerases for Depletion
Authors: Tsao Wei-chung , Buj Raquel , Aird Katherine M. , Sidorova Julia M. , Eckert Kristin A. 
Published: July 2020

AbstractOncogene activation significantly alters DNA replication dynamics, causing replication stress and genome instability. However, little is known about DNA polymerase expression and regulation during oncogene-induced replication stress. We discovered that the Pol α catalytic subunit, Pol δ, Pol η and Pol κ are all depleted in response to H-RasG12Voverexpression in multiple human cell lines. Distinct transcriptional and post-translational mechanisms mediate replicative and specialized DNA polymerase regulation, respectively, and include both MEK-dependent and -independent pathways. Moreover, Pol η depletion is sufficient to induce a senescence-like growth arrest in non-transformed cells. We provide evidence that H-RasG12V-induced polymerase depletion contributes not only to oncogene-induced replication stress, but also to cell cycle checkpoint enforcement. Polymerase degradation is a protective response, associated with improved cell survival in the face of oncogene-induced stress. Our findings significantly impact our understanding of oncogene-induced cellular transformation and suggest that imbalanced polymerase levels may contribute to neoplastic progression.
Design and Development of Point of Care Test and Optical Reader for Early Screening of Kidney Related Disorder
Authors: Shihvare Pankaj , Mohla Satyam , Dube Tejal , Verma Alok , Srivastava Rohit 
Published: July 2020

AbstractLow-cost, paper-based colorimetric assays for early screening of albumin, creatinine and their ratio have been developed. The developed methods are noninvasive and require only 10µl of the urine sample. A reflectance-based optical reader has also been developed for the quantification of the albumin and creatinine. The developed method is based on spot urine testing which is advantageous when compared to the conventional 24-hour urine collection. The detection range of albumin and creatinine assays is 10-150 mg/dl and 25–400 mg/dl, respectively. The developed assays and optical reader were tested with the chronic kidney diseased patient’s samples at KEM Hospital, Mumbai.
A three dimensional human immune-tumor cell model reveals the importance of isotypes in antibody-based immunotherapy
Authors: Lara Sandra , Anania Jessica C. , Virtanen Alexander , Stenhammar Viktoria , Kleinau Sandra 
Published: July 2020

AbstractMonoclonal antibodies (mAb) have revolutionized clinical medicine, especially in the field of cancer immunotherapy. The challenge now is to improve the response rates in the patients, as immunotherapy still fails for many patients. Strategies to enhance tumor cell death is a fundamental aim, but relevant model systems for human tumor immunology are lacking. Herein, we have developed a novel pre-clinical human immune – three-dimensional (3D) tumor model (spheroids) to map the efficiency of tumor-specific isotypes for improved tumor cell killing. Different anti-CD20 Rituximab (RTX) isotypes alone or in combination, were evaluated for mediating complement-dependent cytotoxicity and antibody-dependent phagocytosis by human monocytic cells in 3D spheroids, in parallel with monolayer culture, of human CD20+B-cell lymphoma. We show that the IgG3 variant of RTX has the greatest tumoricidal effect over other isotypes, mediating strong infiltration of monocytic effector cells into 3D spheroids. Hence, the human immune-3D tumor model is an attractiveex vivosystem to help filter out mAbs for best efficacy in cancer immunotherapy.
USP19 modulates cancer cell migration and invasion and acts as a novel prognostic marker in patients with early breast cancer
Authors: Rossi Fabiana A , Steinberg Juliana H Enriqué , Roitberg Ezequiel H Calvo , Joshi Molishree , Pandey Ahwan , Abba Martin C , Dufrusine Beatrice , Buglioni Simonetta , De Laurenzi Vincenzo , Sala Gianluca , Lattanzio Rossano , Espinosa Joaquín M , Rossi Mario 
Published: July 2020

ABSTRACTTumor cell dissemination in cancer patients is associated with a significant reduction in their survival and quality of life. The ubiquitination pathway plays a fundamental role in the maintenance of protein homeostasis both in normal and stressed conditions and its dysregulation has been associated with malignant transformation and invasive potential of tumor cells, thus highlighting its value as a potential therapeutic target. In order to identify novel molecular targets of tumor cell migration and invasion we performed a genetic screen with an shRNA library against ubiquitination pathway-related genes. To this end, we set up a protocol to specifically enrich positive migration regulator candidates. We identified the deubiquitinase USP19 and demonstrated that its silencing reduces the migratory and invasive potential of highly invasive breast cancer cell lines. We extended our investigationin vivoand confirmed that mice injected with USP19 depleted cells display increased tumor-free survival, as well as a delay in the onset of the tumor formation and a significant reduction in the appearance of metastatic foci, indicating that tumor cell invasion and dissemination is impaired. In contrast, overexpression of USP19 increased cell invasiveness bothin vitroandin vivo, further validating our findings. More importantly, we demonstrated that USP19 catalytic activity is important for the control of tumor cell migration and invasion, and that its molecular mechanism of action involves LRP6, a Wnt co-receptor. Finally, we showed that USP19 overexpression is a surrogate prognostic marker of distant relapse in patients with early breast cancer. Altogether, these findings demonstrate that USP19 might represent a novel therapeutic target in breast cancer.
In vivophage display: identification of organ-specific peptides using deep sequencing and differential profiling across tissues
Authors: Pleiko Karlis , Põšnograjeva Kristina , Haugas Maarja , Paiste Päärn , Tobi Allan , Kurm Kaarel , Riekstina Una , Teesalu Tambet 
Published: July 2020

ABSTRACTIn vivophage display is widely used for identification of organ- or disease-specific homing peptides. However, the currentin vivophage biopanning approaches fail to assess biodistribution of specific peptide phages across tissues during the screen, thus necessitating laborious and time-consuming post-screening validation studies on individual peptide phages. Here, we adopted bioinformatics tools used for RNA sequencing for analysis of high throughput sequencing (HTS) data to estimate the representation of individual peptides during biopanningin vivo. The data fromin vivophage screen were analyzed using differential binding – relative representation of each peptide in the target organ vs. in a panel of control organs. Application of this approach in a model study using low-diversity peptide T7 phage library with spiked-in brain homing phage, demonstrated brain-specific differential binding of brain homing phage and resulted in identification of novel lung and brain specific homing peptides. Our study provides a broadly applicable approach to streamlinein vivopeptide phage biopanning and to increase its reproducibility and success rate.Graphic abstractIn vivophage display using differential binding approach
GsERFenhances aluminum tolerance through an ethylene-mediated pathway inArabidopsis thaliana
Authors: Li Lu , Li Xingang , Yang Ce , Cheng Yanbo , Cai Zhandong , Nian Hai , Ma Qibin 
Published: July 2020

AbstractThe ethylene response factor (ERF) transcription factor is a subfamily of AP2/ERF superfamily in plants, which plays multiple roles in plant growth and development as well as stress response. In this study, we found that theGsERFgene from BW69 line of wild soybean held a constitutive expression pattern and induced by aluminum stress with more transcripts in soybean root. The putative GsERF protein containing an AP2 domain was in the nucleus and transactivation activity. In addition, the overexpression of theGsERFgene enhanced root relative length rate in Arabidopsis and shallow staining by hematoxylin under the treatments of AlCl3. The ethylene synthesis related genes such asACS4, ACS5andACS6are upregulated in theGsERFoverexpressed plants than those in wild type plants under the treatment of AlCl3. Furthermore, expression levels of stress/ABA-responsive marker genes, includingABI1, ABI2, ABI4, ABI5, RD29BandRD22in transgenic lines compared with those in wild type Arabidopsis were affected by AlCl3treatments. Taken together, the results indicate that overexpression ofGsERFmay enhance aluminum tolerance through an ethylene-mediated pathway and/or ABA signaling pathway inArabidopsis thaliana.
A psychophysically-tuned computational model of human primary visual cortex produces geometric optical illusions
Authors: Retsa Chrysa , Ariza Ana Hernando , Noordanus Nathanael W. , Ruffoni Lorenzo , Murray Micah M. , Franceschiello Benedetta 
Published: July 2020

AbstractGeometrical optical illusion (GOIs) are mismatches between physical stimuli and perception. GOIs provide an access point to study the interplay between sensation and perception, yet there is scant quantitative investigation of the extent to which different GOIs rely on similar or distinct brain mechanisms. We addressed this knowledge gap. First, 30 healthy adults reported quantitatively their perceptual biases with three GOIs, whose physical properties parametrically varied on a trial-by-trial basis. Biases observed with one GOI were unrelated to those observed with another GOI, suggestive of (partially) distinct underlying mechanisms. Next, we used these psychophysical results to tune a computational model of primary visual cortex that combines parameters of orientation, selectivity, intra-cortical connectivity, and long-range interactions. We showed that similar biases could be generatedin-silico, mirroring those observed in humans. Such results provide a roadmap whereby computational modelling, informed by human psychophysics, can reveal likely mechanistic underpinnings of perception.
TDP-43 proteinopathy alters the ribosome association of multiple mRNAs including the glypican Dally-like protein (Dlp)/GPC6
Authors: Lehmkuhl Erik M , Loganathan Suvithanandhini , Alsop Eric , Blythe Alexander D , Kovalik Tina , Mortimore Nicholas P , Barrameda Dianne , Kueth Chuol , Eck Randall J , Siddegowda Bhavani B , Joardar Archi , Ball Hannah , Macias Maria E , Bowser Robert , Van Keuren-Jensen Kendall , Zarnescu Daniela C 
Published: July 2020

AbstractAmyotrophic lateral sclerosis (ALS) is a genetically heterogeneous neurodegenerative disease in which 97% of patients exhibit cytoplasmic aggregates containing the RNA binding protein TDP-43. Using tagged ribosome affinity purifications inDrosophilamodels of TDP-43 proteinopathy, we identified TDP-43 dependent translational alterations in motor neurons impacting the spliceosome, pentose phosphate and oxidative phosphorylation pathways. A subset of the mRNAs with altered ribosome association are also enriched in TDP-43 complexes suggesting that they may be direct targets. Among these,dlpmRNA, which encodes the glypican Dally like protein (Dlp)/GPC6, a wingless (Wg/Wnt) signaling regulator is insolubilized both in flies and patient tissues with TDP-43 pathology. While Dlp/GPC6 forms puncta in theDrosophilaneuropil and ALS spinal cords, it is reduced at the neuromuscular synapse in flies suggesting compartment specific effects of TDP-43 proteinopathy. These findings together with genetic interaction data show that Dlp/GPC6 is a novel, physiologically relevant target of TDP-43 proteinopathy.
What are the gray and white matter volumes of the human spinal cord?
Authors: Henmar Simon , Simonsen Erik B. , Berg Rune W. 
Published: July 2020

The gray matter of the spinal cord is the seat of somata of various types of neurons devoted to the sensory and motor activities of the limbs and trunk as well as a part of the autonomic nervous system. The volume of the spinal gray matter is an indicator of the local neuronal processing and this can decrease due to atrophy associated with degenerative diseases and injury. Nevertheless, the absolute volume of the human spinal cord has rarely been reported, if ever. Here, we use high–resolution magnetic resonance imaging, with a cross–sectional resolution of 50 × 50μm2and a voxel size of 0.0005mm3, to estimate the total gray and white matter volume of a post mortem human female spinal cord. Segregation of gray and white matter was accomplished using deep learning image segmentation. Further, we include data from a male spinal cord of a previously published study. The gray and white matter volumes were found to be 2.87 and 11.33 ml, respectively for the female and 3.55 and 19.33 ml, respectively for a male. The gray and white matter profiles along the vertebral axis were found to be strikingly similar and the volumes of the cervical, thoracic and lumbosacral sections were almost equal.NEW AND NOTEWORTHYHere, we combine high field MRI (9.4T) and deep learning for a post-mortem reconstruction of the gray and white matter in human spinal cords. We report a minuscule total gray matter volume of 2.87 ml for a female and 3.55 ml for a male. For comparison, these volumes correspond approximately to the distal digit of the little finger.
Milk losses and dynamics during perturbations in dairy cows differ with parity and lactation stage
Authors: Adriaens I. , van den Brulle I. , D’Anvers L. , Statham J.M.E. , Geerinckx K. , De Vliegher S. , Piepers S. , Aernouts B. 
Published: July 2020

ABSTRACTMilk yield dynamics during perturbations reflect how cows respond to challenges. This study investigated the characteristics of 62,406 perturbations from 16,604 lactation curves of dairy cows milked with an automated milking system at 50 Belgian, Dutch and English farms. The unperturbed lactation curve representing the theoretical milk yield dynamics was estimated with an iterative procedure fitting a Wood model on the daily milk yield data not part of a perturbation. Each perturbation was characterized and split in a development and a recovery phase. Based hereon, we calculated both the characteristics of the perturbation as a whole, and the duration, slopes and milk losses in the phases separately. A two-way analysis of variance followed by a pairwise comparison of group means was carried out to detect differences between these characteristics in different lactation stages (early, mid-early, mid-late and late) and parities (first, second and third or higher). On average, 3.8 ± 1.9 (mean ± standard deviation) perturbations were detected per lactation in the first 305 days after calving, corresponding to an estimated 92.1 ± 135.8 kg of milk loss. Only 1% of the lactations had no perturbations. The average development and recovery rates were respectively −2.3 and 1.5 kg per day, and these phases lasted on average 10.1 and 11.6 days. Perturbation characteristics were significantly different across parity and lactation stage groups, and early and mid-early perturbations in higher parities were found to be more severe, with faster development rates, slower recovery rates and higher milk losses. The method to characterize perturbations can be used for precision phenotyping purposes looking into the response of cows to challenges, or for monitoring applications, for example to evaluate the development and recovery of diseases and how these are affected by preventive actions or treatments.
Pinpointing the neural signatures of single-exposure visual recognition memory
Authors: Mehrpour Vahid , Meyer Travis , Simoncelli Eero P. , Rust Nicole C. 
Published: July 2020

AbstractMemories of the images that we have seen are thought to be reflected in the reduction of neural responses in high-level visual areas such as inferotemporal (IT) cortex, a phenomenon known as repetition suppression (RS). We challenged this hypothesis with a task that required rhesus monkeys to report whether images were novel or repeated while ignoring variations in contrast, a stimulus attribute that is also known to modulate the overall IT response. The monkeys’ behavior was largely contrast-invariant, contrary to the predictions of an RS-inspired decoder, which could not distinguish responses to images that are repeated from those of lower contrast. However, the monkeys’ behavioral patterns were well-predicted by a linearly decodable variant in which the total spike count was corrected for contrast modulation. These results suggest that the IT neural activity pattern that best aligns with single-exposure visual recognition memory behavior is not RS but rather “sensory referenced suppression (SRS)”: reductions in IT population response magnitude, corrected for sensory modulation.Significance statementMemories of whether an image has been seen before are reflected in high-level visual cortex as “sensory referenced suppression (SRS)”: reductions in population response magnitude, corrected for sensory modulation.
Using iCn3D and the World Wide Web for structure-based collaborative research: Analyzing molecular interactions at the root of COVID-19
Authors: Youkharibache Philippe , Cachau Raul , Madej Tom , Wang Jiyao 
Published: July 2020

ABSTRACTThe COVID-19 pandemic took us ill-prepared and tackling the many challenges it poses in a timely manner requires world-wide collaboration. Our ability to study the SARS-COV-2 virus and its interactions with its human host in molecular terms efficiently and collaboratively becomes indispensable and mission-critical in the race to develop vaccines, drugs, and neutralizing antibodies. There is already a significant corpus of 3D structures related to SARS and MERS coronaviruses, and the rapid generation of new structures demands the use of efficient tools to expedite the sharing of structural analyses and molecular designs and convey them in their native 3D context in sync with sequence data and annotations. We developed iCn3D (pronounced “I see in 3D”)1to take full advantage of web technologies and allow scientists of different backgrounds to perform and share sequence-structure analyses over the Internet and engage in collaborations through a simple mechanism of exchanging “lifelong” web links (URLs). This approach solves the very old problem of “sharing of molecular scenes” in a reliable and convenient manner. iCn3D links are sharable over the Internet and make data and entire analyses findable, accessible, and reproducible, with various levels of interoperability. Links and underlying data are FAIR2and can be embedded in preprints and papers, bringing a 3D live and interactive dimension to a world of text and static images used in current publications, eliminating at the same time the need for arcane supplemental materials. This paper exemplifies iCn3D capabilities in visualization, analysis, and sharing of COVID-19 related structures, sequence variability, and molecular interactions.