bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pre-metazoan origin of neuropeptide signalling
Authors: Luis Alfonso Yañez-Guerra , Daniel Thiel , Gáspár Jékely 
Published: November 2021

AbstractNeuropeptides are a diverse class of signalling molecules in metazoans. They occur in all animals with a nervous system and also in neuron-less placozoans. However, their origin has remained unclear because no neuropeptide shows deep homology across lineages and none have been found in sponges. Here, we identify two neuropeptide precursors, phoenixin and nesfatin, with broad evolutionary conservation. By database searches, sequence alignments and gene-structure comparisons we show that both precursors are present in bilaterians, cnidarians, ctenophores and sponges. We also found phoenixin and a secreted nesfatin precursor homolog in the choanoflagellate Salpingoeca rosetta. Phoenixin in particular, is highly conserved, including its cleavage sites, suggesting that prohormone processing occurs also in choanoflagellates. In addition, based on phyletic patterns and negative pharmacological assays we question the originally proposed GPR-173 (SREB3) as a phoenixin receptor. Our findings indicate that signalling by secreted neuropeptide homologs has pre-metazoan origins and thus evolved before neurons.
Longitudinal changes of ADHD symptoms in association with white matter microstructure: a tract-specific fixel-based analysis
Authors: Damatac Christienne G. , Soheili-Nezhad Sourena , Freches Guilherme Blazquez , Zwiers Marcel P. , de Bruijn Sanne , Ikde Seyma , Portengen Christel M. , Abelmann Amy C. , Dammers Janneke T. , van Rooij Daan , Akkermans Sophie E. A. , Naaijen Jilly , Franke Barbara , Buitelaar Jan K. , Beckmann Christian F. , Sprooten Emma 
Published: November 2021

AbstractBackgroundVariation in the longitudinal course of childhood attention deficit/hyperactivity disorder (ADHD) coincides with neurodevelopmental maturation of brain structure and function. Prior work has attempted to determine how alterations in white matter (WM) relate to changes in symptom severity, but much of that work has been done in smaller cross-sectional samples using voxel-based analyses. Using standard diffusion-weighted imaging (DWI) methods, we previously showed WM alterations were associated with ADHD symptom remission over time in a longitudinal sample of probands, siblings, and unaffected individuals. Here, we extend this work by further assessing the nature of these changes in WM microstructure by including an additional follow-up measurement (aged 18 – 34 years), and using the more physiologically informative fixel-based analysis (FBA).MethodsData were obtained from 139 participants over 3 clinical and 2 follow-up DWI waves, and analyzed using FBA in regions-of-interest based on prior findings. We replicated previously reported significant models and extended them by adding another time-point, testing whether changes in combined ADHD and hyperactivity-impulsivity (HI) continuous symptom scores are associated with fixel metrics at follow-up.ResultsClinical improvement in HI symptoms over time was associated with more fiber density at follow-up in the left corticospinal tract (lCST) (tmax=1.092, standardized effect[SE]=0.044, pFWE=0.016). Improvement in combined ADHD symptoms over time was associated with more fiber cross-section at follow-up in the lCST (tmax=3.775, SE=0.051, pFWE=0.019). Conclusions: Aberrant white matter development involves both lCST micro- and macrostructural alterations, and its path may be moderated by preceding symptom trajectory.
Patient induced pluripotent stem cell-derived hepatostellate organoids establish a basis for liver pathologies in telomeropathies
Authors: Choi Young-Jun , Kim Melissa S. , Rhoades Joshua H. , Johnson Nicolette M. , Berry Corbett T. , Root Sarah , Chen Qijun , Tian Yuhua , Fernandez Rafael J. , Cramer Zvi , Adams-Tzivelekidis Stephanie , Li Ning , Johnson F. Brad , Lengner Christopher J. 
Published: November 2021

AbstractPatients with dyskeratosis congenita (DC) and related telomeropathies resulting from premature telomere dysfunction suffer from multi-organ failure. In the liver, DC patients present with nodular hyperplasia, steatosis, inflammation, and cirrhosis. We model DC liver pathologies using isogenic human induced pluripotent stem (iPS) cells harboring a causal DC mutation inDKC1, or a clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9-corrected control allele. Differentiation of these iPS cells into hepatocytes or hepatic stellate cells followed by generation of genotype-admixed hepatostellate organoids revealed a dominant phenotype in the parenchyma, with DC hepatocytes eliciting a pathogenic hyperplastic response in stellate cells independent of stellate cell genotype. Pathogenic phenotypes could be rescued via suppression of AKT activity, a central regulator of MYC-driven hyperplasia downstream ofDKC1mutation. Thus, isogenic iPS-derived admixed hepatostellate organoids offer insight into the liver pathologies in telomeropathies and provide a framework for evaluating emerging therapies.
A Comprehensive Roadmap Towards the Generation of an Influenza B Reporter Assay Using a Single DNA Polymerase-Based Cloning of the Reporter RNA Construct
Authors: Kedia Nandita , Banerjee Saptarshi , Mondal Arindam 
Published: November 2021

AbstractMini-genome reporter assay is a key tool for conducting RNA virus research. But, procedural complications and lack of adequate literature pose a major challenge in developing these assay systems. Here, we present a novel yet generic and simple cloning strategy for the construction of influenza B virus reporter RNA template and describe an extensive standardization of the reporter RNP/ polymerase activity assay for monitoring viral RNA synthesis in an infection free setting. Using this assay system, we, for the first time showed the effect of viral protein NS1 and host protein PKC-Delta upon influenza B virus RNA synthesis. Additionally, the assay system showed promising results in evaluating the efficacy of antiviral drugs targeting viral RNA synthesis and virus propagation. Together, this work offers a detailed protocol for standardization of influenza virus mini-genome assay and an excellent tool for screening of host factors and antivirals in a fast, user-friendly and high throughput manner.
On the hindlimb biomechanics of the avian take-off leap
Authors: Meilak E. A. , Provini P. , Palmer C. , Gostling N. J. , Heller M. O. 
Published: November 2021

AbstractAlthough extant land birds take to the air by leaping, generating the initial take-off velocity primarily from the hindlimbs, the detailed musculoskeletal mechanics remain largely unknown. We therefore simulated in silico the take-off leap of the zebra finch, Taeniopygia guttata, a model species of passerine, a class of bird which includes over half of all extant bird species. A 3D computational musculoskeletal model of the zebra finch hindlimb, comprising of 43 musculotendon units was developed and driven with previously published take-off ground reaction forces and kinematics. Using inverse dynamics, the external moments at the ankle, knee, and hip joints were calculated and contrasted to the cumulative muscle capability to balance these moments. Mean peak external flexion moments at the hip and ankle were 0.55 bodyweight times leg length (BWL) each whilst peak knee extension moments were about half that value (0.29 BWL). Muscles had the capacity to generate 146%, 230%, and 212 % of the mean peak external moments at the hip, knee, and ankle, respectively. Similarities in hindlimb morphology and external loading across passerine species suggest that the effective take-off strategy employed by the zebra finch may be shared across the passerine clade and therefore half of all birds.
Loss of self-tolerance leads to altered gene expression and IMD pathway activation inDrosophila melanogaster
Authors: Kr Pooja , Waring-Sparks Ashley L. , Bretz Nicholas M. , Mortimer Nathan T. 
Published: November 2021

ABSTRACTImmune self-tolerance is the ability of a host’s immune system to recognize and avoid triggering immune responses against self-tissue. This allows the host to avoid self-directed immune damage while still responding appropriately to pathogen infection. A breakdown of self-tolerance can lead to an autoimmune state in which immune cells target healthy self-tissue, leading to inflammation and tissue damage. In order to better understand the basic biology of autoimmunity and the role of the innate immune system in maintaining self-tolerance, we have recently characterized theDrosophila melanogaster tuSzautoimmune mutant. This mutant strain can serve as a model of innate immune mediated self-tolerance, and here we identify transcripts that are deregulated in flies experiencing a loss of self-tolerance. We find that these changes include the activation of the Relish/NFκB transcription factor, alterations in transcripts encoding proteins predicted to mediate organismal metabolism, and a downregulation of transcripts linked to developmental processes. We further find that NFκB signaling plays a protective role against loss of self-tolerance inDrosophila.Our findings provide insight into the transcriptional and physiological changes underlying self-tolerance and autoimmunity.
Reset Networks: Emergent Topography by Composition of Convolutional Neural Networks
Authors: Hannagan T. 
Published: November 2021

AbstractWe introduce the Reset model, a composition of neural networks - typically several levels of convolutional neural networks - whose outputs at one level are gathered and reshaped into a spatial input for the next level. We show that units in Reset networks self-organize into clusters when trained on MNIST, Fashion MNIST, CIFAR-10 and CIFAR-100. We then show that a stronger type of self-organization, reminiscent of the topography found for numbers in parietal cortex, arises when number images are mapped onto developmentally realistic number codes. We outline the implications of this model for theories of the cortex and developmental neuroscience.
CLASS-II KNOX genes coordinate spatial and temporal patterns of the tomato ripening
Authors: Keren-Keiserman Alexandra , Shtern Amit , Chalupowicz Daniel , Furumizu Chihiro , Alvarez John Paul , Amsalem Ziva , Arazi Tzahi , Tuvia-Alkalai Sharon , Efroni Idan , Fallik Elazar , Goldshmidt Alexander 
Published: November 2021

AbstractRipening is a complex developmental change of a mature organ, the fruit. In plants like a tomato, it involves softening, pigmentation, and biosynthesis of metabolites beneficial for the human diet. Examination of the transcriptional changes towards ripening suggests that redundant uncharacterized factors may be involved in the coordination of the ripening switch. Previous studies have demonstrated that Arabidopsis CLASS-II KNOX genes play a significant role in controlling the maturation of siliques and their transition to senescence. Here we examined the combined role of all four tomato CLASS-II KNOX genes in the maturation and ripening of fleshy fruits using an artificial microRNA targeting them simultaneously. As expected, the knockdown plants (35S::amiR-TKN-CL-II) exhibited leaves with increased complexity, reminiscent of the leaf phenotype of plants overexpressing CLASS-I KNOX, which antagonize CLASS-II KNOX gene functions. The fruits of 35S::amiR-TKN-CL-II plants were notably smaller than the control. While their internal gel/placenta tissue softened and accumulated the typical pigmentation, the pericarp color break took place ten days later than control, and eventually, it turned yellow instead of red.Additionally, the pericarp of 35S::amiR-TKN-CL-II fruits remained significantly firmer than control even after three weeks of shelf storage. Strikingly, the 35S::amiR-TKN-CL-II fruits showed early ethylene release and respiration peak, but these were correlated only with liquefaction and pigmentation of the internal tissues. Our findings suggest that CLASS-II KNOX genes are required to coordinate the spatial and temporal patterns of tomato fruit ripening.One sentence summaryTomato CLASS-II KNOX genes play antagonistic roles in the regulation of ripening at the internal fruit domains and pericarp.
Cultured deep-sea PVC bacteria shed light on eukaryogenesis
Authors: Zheng Rikuan , Wang Chong , Zhang Tianhang , Tan Yingqi , Sun Chaomin 
Published: November 2021

AbstractEvolutionary relationship between prokaryotes and eukaryotes continues to fascinate biologists. Accumulated studies suggest a eukaryogenesis model based on the PVC (Planctomycetes-Verrucomicrobia-Chlamydiae) bacteria. However, a decisive PVC-based eukaryogenesis scenario has not yet been reported. Here, we isolated PVC bacteria, unique for dividing by budding and for possessing developed endomembrane systems, from the deep sea. In cultured PVC bacterial strains, we detected typical eukaryotic organelle-like structures including endoplasmic reticulum, Golgi apparatus, vesicles, vacuoles and actin/tubulin-based microfilaments. Strikingly, we observed a nucleolus-containing nucleus in a Verrucomicrobia strain, which divides by mitosis. Transcriptomic results further demonstrated abundant presence of genes associated with eukaryotic cellular processes including membrane fusion. We propose that the prominent capability of membrane fusion drives eukaryogenesis by enabling PVC bacteria to evolve eukaryotic cellular features.
RIF1-ASF1-mediated high-order chromatin structure safeguards genome integrity
Authors: Feng Sumin , Ma Sai , Li Kejiao , Gao Shengxian , Ning Shaokai , Shang Jinfeng , Guo Ruiyuan , Blumenfeld Britny , Simon Itamar , Li Qing , Guo Rong , Xu Dongyi 
Published: November 2021

AbstractThe 53BP1-RIF1 pathway antagonizes resection of DNA broken ends and confers PARP inhibitor sensitivity on BRCA1-mutated tumors. However, it is unclear how this pathway suppresses initiation of resection. Here, we identify ASF1 as a partner of RIF1 via an interacting manner similar to its interactions with histone chaperones CAF-1 and HIRA. ASF1 is recruited to distal chromatin flanking DNA breaks by 53BP1-RIF1 and promotes non-homologous end joining (NHEJ) using its histone chaperone activity. Epistasis analysis shows that ASF1 acts in the same NHEJ pathway as RIF1, but via a parallel pathway with the shieldin complex, which suppresses resection after initiation. Moreover, defects in end resection and homologous recombination (HR) in BRCA1- deficient cells are largely suppressed by ASF1 deficiency. Mechanistically, ASF1 compacts adjacent chromatin by heterochromatinization to protect broken DNA ends from BRCA1-mediated resection. Taken together, our findings identified a RIF1-ASF1 histone chaperone complex that promotes changes in high-order chromatin structure to stimulate the NHEJ pathway for DSB repair.
Polyethylene glycol (PEG) methods are superior to acidification for secondary concentration of Adenovirus and MS2 in water
Authors: McLellan N.L. , Weir S.C. , Lee H. , Habash M.B. 
Published: November 2021

ABSTRACTEnteric viruses are a leading cause of waterborne illness worldwide and surveillance studies lack standardization in method selection. The most common and cost-effective approach to concentrating viruses from water samples involves virus adsorption and elution (VIRADEL) procedures, followed by secondary concentration. There is a lack of consistency in how secondary concentration methods are practiced and some methods may have better recovery for particular groups of viruses. Secondary concentration methods typically involve precipitation and the most common methods employ organic flocculation (OF) by acidification at a pH of 3.5, or precipitation by polyethylene glycol (PEG) in combination with the addition of NaCl. In this study, the recovery of coliphage MS2 using the plaque assay and human adenovirus strain 41 (HAdV41) using cell-culture and qPCR assays were evaluated by OF and PEG secondary concentration of spiked samples of wastewater, surface water, and groundwater. The recovery of MS2 and HAdV41 by PEG precipitation was significantly higher than that by OF (p<0.0001) when viruses were detected by culture based methods and marginally better when HAdV41 was enumerated by qPCR (p<0.019). The recovery of HAdV41 by qPCR ranged from 75.3% to 94.4% (n=36). The mean recovery of MS2 by OF was 4.4% (0.9%-7.7%; n=14) and ranged from 57.1% to 87.9% (n=28) for the PEG methods. The poor recovery of MS2 by OF was attributed to inactivation or poor stability at acidic conditions as MS2 were not recovered in the supernatant following OF and centrifugation. The inconsistency and lack of justification for method selection in many studies calls for a systematic study to inform guidance and standardization with respect to the application of concentration methods for various water types and viral pathogens.IMPORTANCEMS2 should not be used as a process control for methods involving acidification and culture-based detection. The dense floc produced by the PEG method may have contributed to higher recoveries as the pellet was more compact and stable than the loose pellet formed by OF. Standard methods for the detection of enteric viruses and surrogates that involve acidification could be modified with PEG precipitation to uphold virus recovery and minimize inactivation.
The social innovation process: exploring the specificities in a developing context
Authors: Morais-da-Silva Rodrigo Luiz , Segatto Andréa Paula , Justen Gelciomar Simão , Bezerra-de-Sousa Indira Gandhi , De-Carli Eduardo 
Published: November 2021

PurposeSocial innovation has been attracting attention in the literature and the practice field due to its intention to create social value. However, the social innovation process is still poorly studied and is marked by several disagreements in the existing models, often built from data coming from developed countries. So, the focus of this study is to answer the following research question: how is the social innovation process configured in a developing context?Design/methodology/approachThe study investigated three cases of Brazilian social innovation processes through a qualitative approach. The authors also use the institutional levels perspectives to analyse the cases.FindingsThe main findings indicate that the social innovation process comprises five phases and occurs between the micro, meso and macro institutional levels. Besides, the social innovation process relies on the participation of different partners, in a non-sequential process, with the possibility of returning from one stage to another and is evaluated continuously over time.Practical implicationsThis study may be useful for social entrepreneurs and their teams in organisations that generate social innovations (such as social enterprises) to understand how well-established initiatives have organised themselves over time. Public policymakers may also use the insights provided to create more favourable environments to create new social innovation initiatives and expand the existing ones.Originality/valueThe characteristics of the social innovation process revealed in this study contributes to the advancement of the area, mainly because it considers the perspective of institutional levels and is based on data from a developing country.
Nonlinear dynamics of a spur gear pair with tooth root crack based on an amplitude modulation function
Authors: Gao Nan , Wang Shiyu , Bajwa Muhammad Asad Ur Rehman 
Published: November 2021

PurposeGear transmissions are widely utilized in practice. This paper aims to uncouple the crack feature from the cracked time-varying mesh stiffness (TVMS) and investigate the effects of the crack on the nonlinear dynamics of a spur gear pair.Design/methodology/approachAn approximate method to simulate the cracked TVMS is proposed by using an amplitude modulation function. The ratio of mesh stiffness loss is introduced to estimate the TVMS with different crack depths and angles. The dynamic responses are obtained by solving a torsional model which takes the non-loaded static transmission error, the backlash and the cracked TVMS into account. By using the bifurcation diagram, the largest Lyapunov exponent (LLE) and dynamic mesh force, the influences of crack on nonlinear behaviors are examined. The dynamic characteristics are identified from the phase diagram, Poincaré map, dynamic mesh force, time series and FFT spectra.FindingsThe comparison between the healthy and cracked gear pairs indicates that the crack affects the system motions, such as the obvious changes of impact force and unpredictable instability. Besides, the additive and difference combination frequencies can be found in periodic-1 and -2 motions, but they are covered in periodic-3 and chaotic motions. Deeper crack is an important determinant of the nonlinear behaviors at a higher speed.Originality/valueThe research provides an interesting perspective on cracked TVMS and reveals the connection between crack and nonlinear behaviors of the gear pairs.
Barriers and facilitators of technological eco-innovations: a multilevel analysis in a Brazilian cosmetics company
Authors: Dugonski Franciany Cristiny Venâncio , Tumelero Cleonir 
Published: November 2021

PurposeThis study analyzed the multilevel barriers and facilitators of technological eco-innovations.Design/methodology/approachThe authors carried out an in-depth case study in a Brazilian cosmetics company, recognized for its eco-innovative initiatives, which has the technological eco-innovation of products as a central sustainability strategy.FindingsThe results contribute to the existing literature, showing that multilevel analysis is effective for minimizing barriers and increasing facilitators, especially through the company's adoption of an eco-innovation strategy and planning methodologies. The authors identified four groups of barriers: market, raw material, governmental and company's internal factors; and four groups of facilitators: legislation, market and technological innovation, communication and environmental management.Originality/valueThe original research results contribute both to the literature and to the companies that aim to implement eco-innovative measures. The results showed that the adoption of innovation strategies and planning methodologies by the company can minimize barriers and enhance facilitators. In addition the fact is that barriers and facilitators of implementing eco-innovations are dynamic factors that require continuous monitoring since they can be a barrier in one circumstance and a facilitator in another.