bluuebunny/crossref_metadata_2025 huggingface dataset:
STRling: a k-mer counting approach that detects short tandem repeat expansions at known and novel loci
Authors: Dashnow Harriet , Pedersen Brent S. , Hiatt Laurel , Brown Joe , Beecroft Sarah J. , Ravenscroft Gianina , LaCroix Amy J. , Lamont Phillipa , Roxburgh Richard H. , Rodrigues Miriam J. , Davis Mark , Mefford Heather C. , Laing Nigel G. , Quinlan Aaron R.
Published: November 2021

Expansions of short tandem repeats (STRs) cause dozens of rare Mendelian diseases. However, STR expansions, especially those arising from repeats not present in the reference genome, are challenging to detect from short-read sequencing data. Such “novel” STRs include new repeat units occurring at known STR loci, or entirely new STR loci where the sequence is absent from the reference genome. A primary cause of difficulty detecting STR expansions is that reads arising from STR expansions are frequently mismapped or unmapped. To address this challenge, we have developed STRling, a new STR detection algorithm that counts k-mers (short DNA sequences of length k) in DNA sequencing reads, to efficiently recover reads that inform the presence and size of STR expansions. As a result, STRling can call expansions at both known and novel STR loci. STRling has a sensitivity of 83% for 14 known STR disease loci, including the novel STRs that cause CANVAS and DBQD2. It is the first method to resolve the position of novel STR expansions to base pair accuracy. Such accuracy is essential to interpreting the consequence of each expansion. STRling has an estimated 0.078 false discovery rate for known pathogenic loci in unaffected individuals and a 0.20 false discovery rate for genome-wide loci in unaffected individuals when using variants called from long-read data as truth. STRling is fast, scalable on cloud computing, open-source, and freely available athttps://github.com/quinlan-lab/STRling.
Evidence for the role of transcription factors in the co-transcriptional regulation of intron retention
Authors: Ullah Fahad , Salton Maayan , Reddy Anireddy SN , Ben-Hur Asa
Published: November 2021

Alternative splicing is a widespread regulatory phenomenon that enables a single gene to produce multiple transcripts. Among the different types of alternative splicing, intron retention is one of the least explored despite its high prevalence in both plants and animals. The recent discovery that the majority of splicing is co-transcriptional has led to the finding that chromatin state affects alternative splicing. Therefore it is plausible that transcription factors can regulate splicing outcomes. We provide evidence for this hypothesis by studying regions of open chromatin in retained and excised introns. Using deep learning models designed to distinguish between regions of open chromatin in retained introns and non-retained introns, we identified motifs enriched in IR events with significant hits to known human transcription factors. Our model predicts that the majority of transcription factors that affect intron retention come from the zinc finger family. We demonstrate the validity of these predictions using ChIP-seq data for multiple zinc finger transcription factors and find strong over-representation for their peaks in intron retention events.

Availability

Source code available at https://github.com/fahadahaf/chromir
Passive Exposure Sparsifies Neural Activity in the Primary Visual Cortex
Authors: Homann Jan , Kim Hyewon , Tank David W. , Berry Michael J.
Published: November 2021

A notable feature of neural activity is sparseness – namely, that only a small fraction of neurons in a local circuit have high activity at any moment. Not only is sparse neural activity observed experimentally in most areas of the brain, but sparseness has been proposed as an optimization or design principle for neural circuits. Sparseness can increase the energy efficiency of the neural code as well as allow for beneficial computations to be carried out. But how does the brain achieve sparse-ness? Here, we found that when neurons in the primary visual cortex were passively exposed to a set of images over several days, neural responses became more sparse. Sparsification was driven by a decrease in the response of neurons with low or moderate activity, while highly active neurons retained similar responses. We also observed a net decorrelation of neural activity. These changes sculpt neural activity for greater coding efficiency.
Indirect effects of parental conflict on conspecific offspring development
Authors: Coughlan J.M.
Published: November 2021

Hybrid Seed Inviability (HSI) is a common barrier in angiosperms. Recent work suggests that the rapid evolution of HSI may, in part, be due to conflict between maternal and paternal optima for resource allocation to developing offspring (i.e. parental conflict). However, parental conflict requires that paternally-derived resource acquiring alleles impose a maternal cost. I test this requirement using three closely related species in theMimulus guttatusspecies complex that exhibit significant HSI and differ in their inferred histories of parental conflict. I show that the presence of hybrid seeds significantly affects conspecific seed size for almost all crosses, such that conspecific seeds are smaller after developing with hybrids from fathers with a stronger history of conflict, and larger after developing with hybrids from fathers with a weaker history of conflict. This work demonstrates a cost of paternally-derived alleles, and also has implications for species fitness in secondary contact.
Label-free adaptive optics single-molecule localization microscopy for whole animals
Authors: Park Sanghyeon , Jo Yonghyeon , Kang Minsu , Hong Jin Hee , Ko Sangyoon , Kim Suhyun , Park Sangjun , Park Hae-Chul , Shim Sang-Hee , Choi Wonshik
Published: November 2021

The specimen-induced aberration has been a major factor limiting the imaging depth of single-molecule localization microscopy (SMLM). Here, we report the application of label-free wavefront sensing adaptive optics to SMLM for deep-tissue super-resolution imaging. The proposed system measures complex tissue aberrations from intrinsic reflectance rather than fluorescence emission and physically corrects the wavefront distortion more than three-fold stronger than the previous limit. This enables us to resolve sub-diffraction morphologies of cilia and oligodendrocytes in whole intact zebrafish as well as dendritic spines in thick mouse brain tissues at the depth of up to 102 μm with localization number enhancement by up to 37 times and localization precision comparable to aberration-free samples. The proposed approach can expand the application range of SMLM to intact animals that cause the loss of localization points owing to severe tissue aberrations.
Polygalacturonase production enhancement by Piriformospora indica from sugar beet pulp under submerged fermentation using surface methodology
Authors: Kiani Somayyeh , Rezaei Parisa Fathi , Jamalzadegan Sina
Published: November 2021

This study proposed a novel and cost-effective approach to enhance and optimize the polygalacturonase from P. indica. In current investigation, the impact of ammonium sulfate, sugar beet pulp (SBP) and glucose as variables on induction of polygalacturonase from P. indica was optimized using the central composite design (CCD) of response surface methodology (RSM) under SmF. Additionally, partial polygalacturonase purification and in situ analysis were performed. The optimal reaction conditions, which resulted in the highest enzyme activity were observed as the following conditions: ammonium sulfate (4 g/L), SBP (20 g/L), glucose (60 g/L). Under the optimized condition, the maximum enzyme activity reached to 19.4 U/ml (127 U/mg) which increased by 5.84 times compared to non-optimized conditions. The partial purified polygalacturonase molecular weight was estimated 60 KDa. In line with the bioinformatic analysis, exo-polygalacturonase sequence of P. indica showed similarity with Rhizoctonia solani’s and Thanateporus cucumeris. These results indicated that SBP act as a cheap and suitable inducer of polygalacturonase production by P. indica in a submerged cultivation. The outcome of this study will be useful for industries to decrease environmental pollution with cost-effective approaches.
Monitoring of SARS-CoV-2 Antibodies Using Dried Blood Spot for At-Home Collection
Authors: Miesse Peyton K. , Collier Bradley B. , Grant Russell P.
Published: November 2021

The utilization of vaccines to fight the spread of SARS-CoV-2 has led to a growing need for expansive serological testing. To address this, an EUA approved immunoassay for detection of antibodies to SARS-CoV-2 in venous serum samples was investigated for use with dried blood spot (DBS) samples. Results from self-collected DBS samples demonstrated a 98.1% categorical agreement to venous serum with a correlation (R) of 0.9600 while professionally collected DBS samples demonstrated a categorical agreement of 100.0% with a correlation of 0.9888 to venous serum. Additional studies were performed to stress aspects of at-home DBS collection, including shipping stability, interference effects, and other sample-specific robustness studies. These studies demonstrated a categorical agreement of at least 95.0% and a mean bias less than ±20.0%. Furthermore, the ability to track antibody levels following vaccination with the BioNTech/Pfizer vaccine was demonstrated with self-collected DBS samples from pre-dose (Day 0) out to 19 weeks.
A genome assembly of the Atlantic chub mackerel (Scomber colias): a valuable teleost fishing resource
Authors: Machado André M. , Gomes-dos-Santos André , Fonseca Miguel , da Fonseca Rute R. , Veríssimo Ana , Felício Mónica , Capela Ricardo , Alves Nélson , Santos Miguel , Salvador-Caramelo Filipe , Domingues Marcos , Ruivo Raquel , Froufe Elsa , Castro L. Filipe C.
Published: November 2021

The Atlantic chub mackerel, Scomber colias Gmelin, 1789, is a medium-size pelagic fish with substantial importance in the fisheries of the Atlantic Ocean and the Mediterranean Sea. Over the past decade, this species has gained special relevance being one of the main targets of pelagic fisheries in the NE Atlantic. Here, we sequenced and annotated the first high-quality draft genome assembly of S. colias, produced with Pacbio HiFi long reads and Illumina Paired-End short reads. The estimated genome size is 814 Mb distributed into 2,028 scaffolds and 2,093 contigs with an N50 length of 4,19 and 3,34 Mb, respectively. We annotated 27,675 protein-coding genes and the BUSCO analyses indicated high completeness, with 97.3 % of the single-copy orthologs in the Actinopterygii library profile. The present genome assembly represents a valuable resource to address the biology and management of this relevant fishery. Finally, this is the fourth high-quality genome assembly within the Order Scombriformes and the first in the genus Scomber.
Chemical Reversible Crosslinking Enables Measurement of RNA 3D Distances and Alternative Conformations in Cells
Authors: Van Damme Ryan , Li Kongpan , Zhang Minjie , Bai Jianhui , Lee Wilson H. , Yesselman Joseph D. , Lu Zhipeng , Velema Willem A.
Published: November 2021

Three-dimensional (3D) structures dictate the functions of RNA molecules in a wide variety of biological processes. However, direct determination of RNA 3D structures in vivo is difficult due to their large sizes, conformational heterogeneity, and dynamics. Here we present a new method, Spatial 2’-Hydroxyl Acylation Reversible Crosslinking (SHARC), which uses chemical crosslinkers of defined lengths to measure distances between nucleotides in cellular RNA. Integrating crosslinking, exonuclease (exo) trimming, proximity ligation, and high throughput sequencing, SHARC enables transcriptome-wide tertiary structure contact maps at high accuracy and precision, revealing heterogeneous RNA structures and interactions. SHARC data provide constraints that improves Rosetta-based RNA 3D structure modeling at near-nanometer resolution. Integrating SHARC-exo with other crosslinking-based methods, we discover compact folding of the 7SK RNA, a critical regulator of transcriptional elongation. These results establish a new strategy for measuring RNA 3D distances and alternative conformations in their native cellular context.
Study on the effect of a triple cancer treatment of propolis, thermal cycling-hyperthermia, and low-intensity ultrasound on PANC-1 cells
Authors: Kuo Yu-Yi , Chen Wei-Ting , Lin Guan-Bo , Lu Chueh-Hsuan , Chao Chih-Yu
Published: November 2021

Background

Pancreatic cancer is a deadly cancer around the world. To reduce side effects and enhance treatment efficacy, study on combination therapy for pancreatic cancer has gained much attention in recent years.

Methods

In this paper, we propose a novel triple treatment combining propolis and two physical stimuli‒thermal cycling-hyperthermia (TC-HT) and low-intensity ultrasound (US) on a human pancreatic cancer cell line PANC-1. MTT assay was used to determine the viability of PANC-1 cells. Flow cytometry was used to detect apoptosis, mitochondrial membrane potential (MMP) loss, and intracellular reactive oxygen species (ROS) levels. Western blot analysis was further performed to measure protein expression and phosphorylation.

Results

The experiments found that, after the triple treatment, the cell viability of the PANC-1 cells decreased to a level 80% less than the control, without affecting the normal pancreatic cells. Another result was excessive accumulation of ROS after the triple treatment, leading to the amplification of apoptotic pathway through the mitogen-activated protein kinase (MAPK) family and mitochondrial dysfunction. Moreover, the combination of TC-HT and US also promotes the anticancer effect of the heat-sensitive chemotherapy drug cisplatin on PANC-1 cells.

Conclusion

This study, to the best of our knowledge, is the first attempt to combine TC-HT, US and a nature compound in cancer treatment. We demonstrate that physical stimuli could augment the therapeutical effect of anticancer agents. It is expected that optimized parameters for different agents and different types of cancer will expand the methodology on oncological therapy in a safe manner.
Pre-metazoan origin of neuropeptide signalling
Authors: Luis Alfonso Yañez-Guerra , Daniel Thiel , Gáspár Jékely
Published: November 2021

Neuropeptides 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

Background

Variation 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).

Methods

Data 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.

Results

Clinical 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

Patients 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

Mini-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

Although 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

Immune 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

We 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

Ripening 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 summary

Tomato 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

Evolutionary 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

The 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

Enteric 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.

IMPORTANCE

MS2 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

Purpose

Social 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/approach

The 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.

Findings

The 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 implications

This 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/value

The 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

Purpose

Gear 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/approach

An 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.

Findings

The 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/value

The 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

Purpose

This study analyzed the multilevel barriers and facilitators of technological eco-innovations.

Design/methodology/approach

The 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.

Findings

The 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/value

The 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.
Earnings quality, foreign investor and dividends
Authors: Lee Jong Hwa
Published: November 2021

This study discovers the relation between corporate governance factors and earnings quality and finds that increases in dividends and foreign ownership deter earnings management. The author shows that dividend increases and foreign ownership enhance earnings quality, but they appear to be substitutes in that role. In other words, as foreign ownership increases, the influence of dividends in increasing earnings quality decreases. Improving transparency through dividend increases and monitoring by foreign institutional investors are substitutes in preventing earnings management.
Cyber-physical-social-information-thinking hyperspace: a manifold of cyberspatial entities
Authors: Kademi Anas Maazu , Koltuksuz Ahmet Hasan
Published: November 2021

Purpose

This paper aims to establish a theoretic framework to provide a fundamental understanding of cyberspatial objects, their existence and their identification scheme while providing a connection between cyber-enabled spaces and cyberspace. It develops an avenue to quantify general philosophical and theoretical questions, precisely, inherently spatial basis that produces an unprecedented space–time continuum, in which cyber-enabled relations evolve.

Design/methodology/approach

Multidisciplinary theoretical approaches are needed to describe complex systems, which in this paper are integrated in a quest for the principles underlying the structural organization and dynamics of cyberspace. A theoretic framework is presented, and the spatial conception of cyber-enabled physical, social, information and thinking spaces and entities existence are provided.

Findings

With spatial objects and spatial properties, cyberspace is inherently spatial. Its basic constructs are founded on its spatial qualities and producing radical space–time compression, cyber-enabled spaces in which dynamic relations develop and thrive. The cyberspatial object operations are primarily built on foundations that depend on physical space and other spatial metaphors. Information space, basically missing in the literature, is an important part of cyberspace.

Research limitations/implications

This work suggested a novel analytical approach to describing cyberspace from broader perspectives and fields. Due to the novelty and divergence of cyber concepts, an interdisciplinary study and methodology are needed. Thus, more research toward theoretical direction could help many of the practical implementations of concepts.

Practical implications

The research is of particular significance in cyberspatial mechanics to describe the dynamics and behavior of cyber physical systems. For example, object-based analysis functions like spatial query, node pattern analysis, cluster analysis, spatial similarity analysis and location modeling.

Originality/value

Complementing the existing literature and defining information space to the research sphere, a theoretical framework providing a fundamental understanding of cyberspatial objects and the general cyberspace foundation has been proposed, resulting in a formalized concept of existence, interactions and applications and services, with respect to philosophy, science and technology, respectively.
Variation of non‐structural carbohydrates across the fast–slow continuum in Amazon Forest canopy trees
Authors: Signori‐Müller Caroline , Oliveira Rafael S. , Valentim Tavares Julia , Carvalho Diniz Francisco , Gilpin Martin , de V. Barros Fernanda , Marca Zevallos Manuel J. , Salas Yupayccana Carlos A. , Nina Alex , Brum Mauro , Baker Timothy R. , Cosio Eric G. , Malhi Yadvinder , Monteagudo Mendoza Abel , Phillips Oliver L. , Rowland Lucy , Salinas Norma , Vasquez Rodolfo , Mencuccini Maurizio , Galbraith David
Published: November 2021

Tropical tree species span a range of life‐history strategies within a fast–slow continuum. The position of a species within this continuum is thought to reflect a negative relationship between growth and storage, with fast‐growing species allocating more carbon to growth and slow‐growing species investing more in storage. For tropical species, the relationship between storage and life‐history strategies has been largely studied on seedlings and less so in adult trees.

We evaluated how stored non‐structural carbohydrates (NSC) vary across adult trees spanning the fast–slow continuum in the Peruvian Amazon by: (a) analysing whole‐tree NSC in two species of contrasting growth and (b) investigating the relationships with key life‐history traits across a broader set of species.

Our results are consistent with a growth–storage trade‐off. The analysis of whole‐tree NSC revealed that the slow‐growing Eschweilera coriacea stored about 2.7 times as much NSC as the fast‐growing Bixa arborea due to markedly higher storage in woody stems and roots. B. arborea also had higher seasonality in NSC, reflecting its strong seasonality in stem growth. Across a range of species, stem starch was negatively related to species growth rate and positively related to wood density.

Given the role of NSC in mediating plants' response to stress, our results suggest that slow‐growing species with greater storage reserves may be more resilient to drought than fast‐growing species.
A multi‐site method to capture turnover in rare to common interactions in bipartite species networks
Authors: Henriksen Marie V. , Latombe Guillaume , Chapple David G. , Chown Steven L. , McGeoch Melodie A.
Published: November 2021

Ecological network structure is maintained by a generalist core of common species. However, rare species contribute substantially to both the species and functional diversity of networks. Capturing changes in species composition and interactions, measured as turnover, is central to understanding the contribution of rare and common species and their interactions. Due to a large contribution of rare interactions, the pairwise metrics used to quantify interaction turnover are, however, sensitive to compositional change in the interactions of, often rare, peripheral specialists rather than common generalists in the network.

Here we expand on pairwise interaction turnover using a multi‐site metric that enables quantifying turnover in rare to common interactions (in terms of occurrence of interactions). The metric further separates this turnover into interaction turnover due to species turnover and interaction rewiring.

We demonstrate the application and value of this method using a host–parasitoid system sampled along gradients of environmental modification.

In the study system, both the type and amount of habitat needed to maintain interaction composition depended on the properties of the interactions considered, that is, from rare to common. The analyses further revealed the potential of host switching to prevent or delay species loss, and thereby buffer the system from perturbation.

Multi‐site interaction turnover provides a comprehensive measure of network change that can, for example, detect ecological thresholds to habitat loss for rare to common interactions. Accurate description of turnover in common, in addition to rare, species and their interactions is particularly relevant for understanding how network structure and function can be maintained.
Mothers and Queens. Religious Metaphors and Marian Devotion Surrounding Isabel II (1833–1868) in Spain*
Authors: Martínez Vilches David
Published: November 2021

This article addresses the use of the parallelisms between the Holy Virgin and Isabel II in the building of the Spanish liberal monarchy's public image (1833–1868). Just like Mary, who was the mother of her child and the mother of Catholics, Isabel II projected her “motherly feelings” beyond her own family to the whole nation through religious metaphors which exhibited her symbolic motherhood. This emotional display of piety, which took place in several Marian shrines of the Spanish geography, was a nationalising and moralising component of the liberal state's attempt to get the crown closer to the citizens. Nevertheless, the symbolic use of religion was a double‐edged sword because the queen's sexual behaviour challenged the model of Catholic femininity, so that republicans and Progressives made use of this contradiction between religious discourses and private life to attack the monarchy.
Do U.S. Investors Value Foreign Component Auditors?
Authors: CHEN BINGYI , CONAWAY JENELLE K.
Published: November 2021

We examine whether investors consider foreign component auditors when assessing the value of U.S. multinational corporations (MNCs) using two sets of Public Company Accounting Oversight Board (PCAOB) international regulatory events. We find investors react negatively when the PCAOB is denied access to inspect foreign component auditors in jurisdictions where a U.S. MNC has significant operations and positively when those countries later allow inspection. For foreign component auditors that are inspected, we find investors react positively when they receive clean inspection reports and negatively when they fail to remediate quality control deficiencies. Consistent with PCAOB international oversight providing additional assurance about foreign component auditor quality, our collective results indicate investors consider foreign component auditors when valuing U.S. MNCs.
Costs of an environmental regulation in livestock farming: Evidence from pig production in rural China
Authors: Chen Shuai , Ji Chen , Jin Songqing
Published: November 2021

We investigate the cost and benefit of one of the most stringent Chinese environmental regulations that led to a shutdown of a large number of livestock farms. The temporal and spatial variation in programme implementation allows us to employ a staggered difference‐in‐difference (DID) to identify the causal effects of the regulation. Our DID estimates show that while the regulation significantly reduced NH3‐N, it has no significant effect on the other three important livestock related pollutants (pH, DO and COD). In contrast, the regulation consistently reduced the number of pigs slaughtered, inventory of live pigs and pork production by 8.3%, 10.3% and 11.2%, which alone is equivalent to a 2.9 percentage point loss of China's entire agricultural output value in 2016. Further analyses reveal evidence of partial substitution between pig and other livestock animals and the possibility of relocation to other regions. The policy‐induced reduction in export and increase in pork price is consistent with the reduction of pig and pork production. Overall, we find that the regulation achieved rather limited environmental benefit at a large economic cost.