bluuebunny/crossref_metadata_2025_split huggingface dataset:
The growth and expansion of meningeal lymphatic networks are affected in craniosynostosis
Authors: Ang Phillip , Matrongolo Matt , Tischfield Max A 
Published: August 2021

AbstractCongenital skull malformations are associated with vascular anomalies that can impair fluid balance in the central nervous system. We previously reported that humans with craniosynostosis and mutations in TWIST1 have dural venous sinus malformations. It is still unknown whether meningeal lymphatic networks, which are patterned alongside the venous sinuses, are also affected. Using a novel skull flat mounting technique, we show that the growth and expansion of meningeal lymphatics are perturbed in Twist1 craniosynostosis models. Changes to the local meningeal environment, including hypoplastic dura and venous malformations, affect the ability of lymphatic networks to sprout and remodel. Dorsal networks along the transverse sinus are hypoplastic with reduced branching. By contrast, basal networks closer to the skull base are more variably affected, showing exuberant growth in some animals suggesting they are compensating for vessel loss in dorsal networks. Injecting molecular tracers into cerebrospinal fluid reveals significantly less drainage to the deep cervical lymph nodes, indicative of impaired lymphatic function. Collectively, our results show that meningeal lymphatic development is hindered in craniosynostosis, suggesting central nervous system waste clearance may be impeded.
Antibodies anti-SARS-CoV2 time-course in patients and vaccinated subjects: an evaluation of the harmonization of two different methods
Authors: Dittadi Ruggero , Seguso Mara , Bertoli Isabella , Afshar Haleh , Carraro Paolo 
Published: August 2021

AbstractThe time-course of antibodies anti SARS-CoV2 is not yet well elucidated, especially in people who underwent a vaccination campaign. In this study we measured antibodies anti-S1 and anti-RBD with two different methods both in patients and in vaccinated subjects.108 specimens from 48 patients diagnosed as COVID-19 affected (time from the onset of symptoms from 3 to 368 days) and 60 specimens from 20 vaccinated subjects (collected after 14 days from the first dose, 14 days and 3 months after a second dose of Comirnaty) were evaluated.We used an ELISA method that measure IgG against anti-Spike 1 and a chemiluminescence immunoassays that measure IgG anti-RBD.In the patients, antibodies concentrations tend to decline after a few months with both methods, but persist relatively high up to nearly a year after symptoms.In vaccinated subjects, antibodies were already detectable after the first dose, but after the booster they show a significant increase. However, the decrease is rapid, given that after 3 months after the second vaccination they are reduced to less than a quarter.The conversion of the results into BAU units improves the relationship between the two methods. However, in vaccinated subjects there was no evidence of proportional error after the conversion, while in the patients the difference between the two methods remained significant.
Drone honey bees (Apis mellifera) are disproportionately sensitive to abiotic stressors despite expressing high levels of stress response proteins
Authors: McAfee Alison , Metz Bradley , Milone Joseph P , Foster Leonard J , Tarpy David R 
Published: August 2021

AbstractDrone honey bees (haploid males) are the obligate sexual partners of queens, and the availability of healthy, high-quality drones directly affects a queen’s fecundity and productivity of her subsequent colony. Yet, our understanding of how stressors affect drone fecundity and physiology is presently limited. We investigated sex biases in susceptibility to abiotic stressors (cold stress, topical imidacloprid exposure, and topical exposure to a realistic cocktail of pesticides), and we found that drones were more sensitive to cold and imidacloprid exposure but the cocktail was not toxic at the concentrations tested. We corroborated this lack of apparent toxicity with in-hive cocktail exposures via pollen feeding. We then used quantitative proteomics to investigate protein expression profiles in the hemolymph of topically exposed workers and drones, and we show that drones express surprisingly high levels of putative stress response proteins relative to workers. Drones apparently invest in strong constitutive expression of damage-mitigating proteins for a wide range of stressors, yet they are still sensitive to stress when challenged. The robust expression of stress-response proteins suggests that drone stress tolerance systems are fundamentally rewired relative to workers, and their susceptibility to stress depends on more than simply gene dose or deleterious recessive alleles.
Human transcriptional gene regulatory network compiled from 14 data resources
Authors: Muley Vijaykumar Yogesh , König Rainer 
Published: August 2021

AbstractTranscriptional regulatory network (TRN) orchestrates spatio-temporal expression of genes to generate cellular responses for survival. The transcription factors (TF) regulating expression of their target genes (TG) are the fundamental units of TRN. Several databases have been developed to catalogue human TRN based on low- and high-throughput experimental and computational studies considering their importance in understanding cellular physiology. However, literature lacks comparative assessment on the strength and weakness of each database. In this study, we compared over 2.2 million regulatory pairs between 1,379 TF and 22,518 TG assembled from 14 data resources. Our study reveals that the TF and TG were common across data resources but not their regulatory pairs. We observed that the TF and TG of the regulatory pairs showed weak expression correlation, significant gene ontology overlap, co-citations in PubMed and low numbers of TF-TG pairs representing transcriptional repression relationships. Furthermore, each TF-TG regulatory pair assigned a combined confidence score reflecting its reliability based on its presence in multiple databases and co-expression. The TRN containing 2,246,598 TF-TG pairs, of which, 44,284 with the information on TF’s activating or repressing effects on their TG is available upon request. This study brings the information about transcriptional regulation scattered over the literature and databases at one place in the form of one of the most comprehensive and complete human TRNs assembled to date, which will be a valuable resource for benchmarking TRN prediction tools, and to the scientific community working in functional genomics, gene expression and gene regulation analysis.
Membrane cholesterol interferes with tyrosine phosphorylation but facilitates the clustering and signal transduction of EGFR
Authors: Hiroshima Michio , Abe Mitsuhiro , Tomishige Nario , Hullin-Matsuda Françoise , Makino Asami , Ueda Masahiro , Kobayashi Toshihide , Sako Yasushi 
Published: August 2021

SummaryEpidermal growth factor receptor (EGFR) activates major cell signaling pathways that regulate various cell responses. Its dimerization and clustering coupled with its lateral mobility are critical for EGFR function, but the contribution of the plasma membrane environment to EGFR function is unknown. Here we show, using single-molecule analysis, that EGFR mobility and clustering are altered by the depletion of cholesterol or sphingomyelin, major lipids of membrane subdomains, causing significant changes in EGFR signaling. When cholesterol was depleted, the subdomain boundary in EGFR diffusion disappeared, the fraction of EGFR pre-dimers was increased, and the ligand-induced phosphorylation of EGFR was enhanced. In addition, the depletion of either lipid prevented the formation of immobile clusters after EGF association and decreased the phosphorylation of downstream proteins. Our results revealed that cholesterol plays dichotomous roles in the signaling pathway of EGFR and that clustering in the membrane subdomains is critical for EGFR signal transduction.
Dual avatars of E. coli grxB encoded Glutaredoxin 2 perform ascorbate recycling and ion channel activities
Authors: Sreekumar Sreeshma Nellootil , Das Bhaba Krishna , Raina Rahul , Puthumadathil Neethu , Udinia Sonakshi , Kumar Amit , Sahoo Sibasis , Ravichandran Pooja , Kumar Suman , Ray Pratima , Kumar Dhiraj , Chandele Anmol , Mahendran Kozhinjampara R. , Arockiasamy Arulandu 
Published: August 2021

AbstractGlutaredoxins (Grxs) are single-domain redox enzymes of the thioredoxin superfamily, and primarily function as glutathione (GSH) dependent disulphide reductases. Whereas, the E. coli Glutaredoxin 2 (EcGrx2) encoded by grxB has two conserved GST-fold domains, it still lacks a classical Grx-like functions. In this study, we show for the first time, that EcGrx2 exists in both soluble and membrane integrated forms. The soluble form associates with a previously unidentified GSH dependent dehydroascrobate (DHA) reductase, and the membrane integrated form possesses ion channel activities. Using enzyme kinetic data and structural data we unequivocally demonstrate that EcGrx2 recycles ascorbate (AsA) from DHA. This ability to recycle AsA is inhibited by Zinc (Zn2+). We also show that both wildtype and the E. coli grxB deletion mutant can be rescued from H2O2-induced oxidative stress using ascorbate as an antioxidant, which otherwise is only known as a carbon source in bacteria. Moreover, the grxB- mutant is susceptible to intracellular killing by ROS producing macrophages. We further discovered that EcGrx2 integrates into the native E. coli membrane and show that the purified soluble protein readily inserts into artificial lipid bilayer membrane and conducts ions in vitro. Our data demonstrates a highly conserved functional similarity among EcGrx2-orthologs and highlights that the utilization and subsequent recycling of ascorbate as an antioxidant by grxB harbouring gram-negative bacteria, including human pathogens, may provide a survival advantage under hostile oxidative environments.
Vectofusin-1–based T-cell transduction approach compared with RetroNectin-based transduction for generating murine chimeric antigen receptor T-cells
Authors: Patel Romil , Devashish Kartik , Singh Shubhra , Nath Pranay , Gohel Dev , Prasad Rishika , Singh Manisha , Saini Neeraj 
Published: August 2021

AbstractGene transfer into human and murine T-cells using viral-based approaches has several promising therapeutic applications including the production of chimeric antigen receptor T-cell (CAR-T) therapy. The generation of murine CAR-T is paramount to test and validate immunocompetent mouse models for CAR-T therapy. Several viral transduction enhancers already exist for gene therapy with few limitations. In this study, we tested vectofusin-1, a short cationic peptide, as a soluble transduction enhancer for gammaretroviral transduction for the generation of anti-CD19 murine CAR-T. We found that in comparison to Retronectin, Vectofusin-1 is an equally optimal transduction enhancer for the generation of murine CAR-T cells.
DNA damage signaling regulates cohesin stabilization and promotes meiotic chromosome axis morphogenesis
Authors: Yu Zhouliang , Dernburg Abby F. 
Published: August 2021

AbstractA hallmark of meiosis is the reorganization of chromosomes as linear arrays of chromatin loops around a chromosome axis comprised of cohesins and regulatory proteins. Defective axis morphogenesis impairs homolog pairing, synapsis, and recombination. We find that axis assembly inC. elegansis promoted by DNA Damage Response (DDR) signaling activated at meiotic entry. Central to this regulation is downregulation of the cohesin release factor WAPL-1 by the DDR transducer kinase ATM-1, which is activated by the meiotic kinase CHK-2. Additional cohesin regulators, including ECO-1 and PDS-5, also contribute to stabilizing axis-associated cohesins. We find that downregulation of WAPL by ATM also promotes cohesin enrichment at DNA damage foci in cultured mammalian cells. Our findings reveal that the DDR and Wapl play conserved roles in cohesin regulation in meiotic prophase and proliferating cells.One-Sentence SummaryDNA Damage Response kinase ATM phosphorylates WAPL to promote meiotic chromosome axis assembly and DNA repair
Endothelial cell signature in muscle stem cells validated by VEGFA-FLT1-AKT1 axis promoting survival of muscle stem cell
Authors: Verma Mayank , Asakura Yoko , Wang Xuerui , Zhou Kasey , Ünverdi Mahmut , Kann Allison P. , Krauss Robert S. , Asakura Atsushi 
Published: August 2021

AbstractEndothelial and skeletal muscle lineages arise from common embryonic progenitors. Despite their shared developmental origin, adult endothelial cells (ECs) and muscle stem cells (MuSCs) (satellite cells) have been thought to possess distinct gene signatures and signaling pathways. Here we shift this paradigm by uncovering how adult MuSC behavior is affected by the expression of a subset of EC transcripts. We used several computational analyses including single-cell RNAseq to show that MuSCs express low levels of canonical EC markers. We demonstrate that MuSC survival is regulated by one such prototypic endothelial signaling pathway (VEGFA-FLT1). Using pharmacological and genetic gain- and loss-of-function studies, we identify the FLT1-AKT1 axis as the key effector underlying VEGFA-mediated regulation of MuSC survival. All together, our data support that the VEGFA-FLT1-AKT1 pathway promotes MuSC survival during muscle regeneration, and highlights how the minor expression of select transcripts is sufficient for affecting cell behavior.
Spatial proteomics reveals subcellular reorganization in human keratinocytes exposed to UVA light
Authors: Valerio Hellen Paula , Ravagnani Felipe Gustavo , Candela Angela Paola Yaya , da Costa Bruna Dias Carvalho , Ronsein Graziella Eliza , Di Mascio Paolo 
Published: September 2021

SummaryThe effects of UV light on the skin have been extensively investigated. However, systematic information about how exposure to UVA light, the least energetic but the most abundant UV radiation reaching the Earth, shapes the subcellular organization of proteins is lacking. Using subcellular fractionation, mass spectrometry-based proteomics, machine learning algorithms, immunofluorescence, and functional assays, we mapped the subcellular reorganization of the proteome of human keratinocytes in response to UVA light. Our workflow quantified and assigned subcellular localization for over 1600 proteins, of which about 200 were found to redistribute upon UVA exposure. Reorganization of the proteome affected modulators of signaling pathways, cellular metabolism, and DNA damage response. Strikingly, mitochondria were identified as one of the main targets of UVA-induced stress. Further investigation demonstrated that UVA induces mitochondrial fragmentation, up-regulates redox-responsive proteins and attenuates respiratory rates. These observations emphasize the role of this radiation as a potent metabolic stressor in the skin.
Geometry of left-invariant Randers metric on the Heisenberg groups
Authors: Fasihi-Ramandi Ghodratallah , Azami Shahroud 
Published: August 2021

PurposeIn this paper, we consider the Heisenberg groups which play a crucial role in both geometry and theoretical physics.Design/methodology/approachIn the first part, we retrieve the geometry of left-invariant Randers metrics on the Heisenberg group H2n+1, of dimension 2n + 1. Considering a left-invariant Randers metric, we give the Levi-Civita connection, curvature tensor, Ricci tensor and scalar curvature and show the Heisenberg groups H2n+1 have constant negative scalar curvature.FindingsIn the second part, we present our main results. We show that the Heisenberg group H2n+1 cannot admit Randers metric of Berwald and Ricci-quadratic Douglas types. Finally, the flag curvature of Z-Randers metrics in some special directions is obtained which shows that there exist flags of strictly negative and strictly positive curvatures.Originality/valueIn this work, we present complete Reimannian geometry of left invarint-metrics on Heisenberg groups. Also, some geometric properties of left-invarainat Randers metrics will be studied.
Surprise: challenging design perceptions in immersive virtual reality environments? The case of designing a hospital project using a CAVE (Cave Automatic Virtual Environment)
Authors: Maftei Laura , Harty Chris 
Published: September 2021

PurposeThe purpose of this paper is to examine how the use of immersive virtual reality (IVR) impacts on the surprise aspects of designing.Design/methodology/approachThe empirical case is a new hospital in the UK wherein a CAVE (Cave Automatic Virtual Environment) type of an IVR environment was used performing six design review sessions during the bid preparation stage. Drawing from a former video-based study, the authors conducted follow-up discussions with the participants to access their perspectives on design surprises emerging from their engagement with the IVR. The study developed a reflective methodology, interviewing participants about their experiences of doing design in the immersive environment. Retrospective discussions were conducted in a data review format, through playing back video clips of the IVR design sessions and asking the participants to reflect on their IVR design experience and on design surprises emerging from their engagement with the IVR.FindingsThe findings indicate that IVRs, such as the CAVE, are not only enhancing existing understandings of design but also challenging the participants' understanding of the design as they experience the immersive version of it, provoking ruptures in current procedures and driving unanticipated changes to the design.Originality/valueThis qualitative study of surprise in design work using IVRs (for a real-life design project) brings new insights into emerging practices of designing using immersive technology, such as the CAVE.
Tell me more and make me feel proud: the role of eco-labels and informational cues on consumers' food perceptions
Authors: Donato Carmela , D'Aniello Alba 
Published: August 2021

PurposeThe objective of the present research is to identify the impact of food-related and packaging-related eco-labels on consumers' perceptions of food quality and safety when an ecological claim, which explains the eco-label meaning, is provided.Design/methodology/approachOne survey (N = 472) plus one experimental lab study were used to test the hypotheses drawn from the elaboration likelihood model. The research employed a 2 (eco-label: MSC vs FSC) × 2 (ecological claim: present vs absent) between-subjects design plus a control condition (i.e. absence of eco-label).FindingsWhen the ecological claim is absent, only food-related eco-labels were found to generate a higher food evaluation. However, when the ecological claim is present, both eco-label types (i.e. food-related and packaging-related) increased food perceptions of quality and safety because of higher feelings of pride.Originality/valueFrom a theoretical perspective, this research identifies both food- and packaging-related eco-labels as extrinsic cues able to affect consumers' perception of food quality and safety. Moreover, the findings of this study present practical implications for package design and health policymaking.
Vacuum oven drying of mussels: mathematical modeling, drying characteristics and kinetics study
Authors: İsmail Osman , Gökçe Kocabay Özlem 
Published: August 2021

PurposeThe aim of this work was to study the effect of the different temperatures on drying kinetics and quality parameters of vacuum oven-dried mediterranean or black mussel (Mytilus galloprovincialis) specimens.Design/methodology/approachDrying process was performed at 50, 60 and 70 °C and a vacuum drying pressure of 0.1 kPa. The proximate composition analysis was done. Drying rates of the mussels were computed. Mathematical modeling was carried out. Effective moisture diffusivity, activation energy and total energy consumption were calculated. Color measurement was conducted.FindingsDrying took place entirely in the falling rate period. The obtained results indicated that the drying air temperature has a remarkable influence on the moisture content and drying rate. Drying resulted in a significant increasing of protein and fat content. The Deff values ranged from 1.44 × 10−9–3.23 × 10−9 m2/s, with the activation energy 4.47 kW kg−1. The Alibas model is the most proper model to define the drying curves. This method provided high energy efficiency and quality in dried products.Research limitations/implicationsFresh mussels grown in Eceabat location were used as the study sample. In the drying process, 50, 60, 70 °C temperatures and 0.1 kPa pressure was used. These are the limitations of the research.Originality/valueThis work is the first to report the influence of vacuum oven drying on the color changes and drying kinetics of black mussels.
Does cooperative membership impact the yield and efficiency of smallholder farmers? Evidence from potato farmers in Mongolia
Authors: Ahado Samuel , Hejkrlík Jiří , Enkhtur Anudari , Tseren Tserendavaa , Ratinger Tomáš 
Published: August 2021

PurposeThe purpose of this paper is to examine the impact of agricultural cooperative membership on potato production and technical efficiency.Design/methodology/approachA combination of propensity score matching technique and sample selection stochastic frontier framework that addresses potential selection bias due to observable and unobservable attributes is used to estimate the effect of participation between cooperative members and non-members. Using a stochastic meta-frontier approach, the technical efficiency of farmers was estimated and compared.FindingsThe empirical results show that the effect of participation in agricultural cooperatives is associated with increased yield and technical efficiency. A comparison of group-specific frontiers indicates that cooperative members perform better than non-members. Cooperative membership decisions is significantly associated with household and farm characteristics (e.g. education, participation in off-farm work, total farmland, distance to market and geographic location).Practical implicationsThe findings of this study demonstrate that cooperative organisations can be an important tool to enhance the productivity and efficiency of smallholder farmers. Successful cooperative models together with training programs designed to enlighten farmers on the importance and tangible benefits of collective action should be used to enlarge participation in cooperative organisations. In addition, governments and development agencies should implement targeted investment and capacity building programs related to irrigation management, gender-sensitive awareness and development of the internal institutional mechanisms in cooperatives for the transfer of knowledge and mutual learning so that all members benefit from cooperatives.Originality/valueDespite the pervasive evidence of the impact of cooperatives on productivity and technical efficiency in the Asian region, this study is probably the first attempt in the crop sector in Mongolia. It provides a rigorous empirical analysis of the impact of agricultural cooperative membership on potato production and technical efficiency through a counterfactual design.