bluuebunny/crossref_metadata_2025 huggingface dataset:
A validated hypoxia-inducible factor (HIF) signature across tissue compartments predicts clinical outcome in human lung fibrosis
Authors: Zhou Yilu , Ewing Rob , Davies Donna E. , Wang Yihua , Jones Mark
Published: January 2022

We previously reported that oxidative stress drives pseudohypoxic hypoxia-inducible factor (HIF) pathway activation to promote pathogenetic collagen structure-function in human lung fibrosis (Brereton et al., 2022). Here, through bioinformatic studies we investigate HIF pathway activation status in patients with idiopathic pulmonary fibrosis (IPF) and whether this has prognostic significance. Applying a well-established HIF gene expression signature, we classified publicly available datasets into HIF score-high and score-low groups across multiple tissue compartments. TheHIF scores in lung tissue, bronchoalveolar lavage (BAL) and peripheral blood mononuclear cells (PBMC) were increased in IPF patients and significantly correlated with an oxidative stress signature consistent with pseudohypoxic HIF pathway activation. A high HIF score in BAL and in PBMC was a strong independent predictor of mortality in multivariate analysis. Thus, a validated HIF gene signature predicts survival across tissue compartments in IPF and merits prospective study as a non-invasive biomarker of lung fibrosis progression.
Racial/ethnic disparities in exposure to COVID-19, susceptibility to COVID-19 and access to health care - findings from a U.S. national cohort
Authors: Robertson McKaylee , Shamsunder Meghana , Brazier Ellen , Mantravadi Mekhala , Rane Madhura S , Westmoreland Drew A , Parcesepe Angela , Zimba Rebecca , Maroko Andrew R , Kulkarni Sarah , Grov Christian , Nash Denis
Published: January 2022

We examined the influence of racial/ethnic differences in socioeconomic position on COVID-19 seroconversion and hospitalization within a community-based prospective cohort enrolled in March 2020 and followed through October 2021 (N=6740). The ability to social distance as a measure of exposure to COVID-19, susceptibility to COVID-19 complications, and access to healthcare varied by race/ethnicity with non-white participants having more exposure risk and more difficulty with healthcare access than white participants. Participants with more (versus less) exposure had greater odds of seroconversion (aOR:1.64, 95% Confidence Interval [CI] 1.18-2.29). Participants with more susceptibility and more barriers to healthcare had greater odds of hospitalization (respective aOR:2.36; 1.90-2.96 and 2.31; 1.69-2.68). Race/ethnicity positively modified the association between susceptibility and hospitalization (aORnon-White:2.79, 2.06-3.78). Findings may explain the disproportionate burden of COVID-19 infections and complications among Hispanic and non-Hispanic Black persons. Primary and secondary prevention efforts should address disparities in exposure, COVID-19 vaccination, and treatment.
Developmental origins of cell heterogeneity in the human lung
Authors: Sountoulidis Alexandros , Salas Sergio Marco , Braun Emelie , Avenel Christophe , Bergenstråhle Joseph , Vicari Marco , Czarnewski Paulo , Theelke Jonas , Liontos Andreas , Abalo Xesus , Andrusivová Žaneta , Asp Michaela , Li Xiaofei , Hu Lijuan , Sariyar Sanem , Casals Anna Martinez , Ayoglu Burcu , Firsova Alexandra , Michaëlsson Jakob , Lundberg Emma , Wählby Carolina , Sundström Erik , Linnarsson Sten , Lundeberg Joakim , Nilsson Mats , Samakovlis Christos
Published: January 2022

The lung contains numerous specialized cell-types with distinct roles in tissue function and integrity. To clarify the origins and mechanisms generating cell heterogeneity, we created a first comprehensive topographic atlas of early human lung development. We report 83 cell states, several spatially-resolved developmental trajectories and predict cell interactions within defined tissue niches. We integrated scRNA-Seq and spatial transcriptomics into a web-based, open platform for interactive exploration. To illustrate the utility of our approach we show distinct states of secretory and neuroendocrine cells, largely overlapping with the programs activated either during lung fibrosis or small cell lung cancer progression. We define the origin of uncharacterized airway fibroblasts associated with airway smooth muscle in bronchovascular bundles, and describe a trajectory of Schwann cell progenitors to intrinsic parasympathetic neurons controlling bronchoconstriction. Our atlas provides a rich resource for further research and a reference for defining deviations from homeostatic and repair mechanisms leading to pulmonary diseases.
Circadian and diel regulation of photosynthesis in the bryophyte Marchantia polymorpha
Authors: Cuitun-Coronado David , Rees Hannah , Colmer Joshua , Hall Anthony , de Barros Dantas Luíza Lane , Dodd Antony N.
Published: January 2022

Circadian rhythms are 24-hour biological cycles that align metabolism, physiology and development with daily environmental fluctuations. Photosynthetic processes are governed by the circadian clock in both flowering plants and some cyanobacteria, but it is unclear how extensively this is conserved throughout the green lineage. We investigated the contribution of circadian regulation to aspects of photosynthesis in Marchantia polymorpha, a liverwort that diverged from flowering plants early in the evolution of land plants. First, we identified in M. polymorpha the circadian regulation of photosynthetic biochemistry, measured using two approaches (delayed fluorescence, PAM fluorescence). Second, we identified that light-dark cycles synchronize the phase of 24 h cycles of photosynthesis in M. polymorpha, whereas the phases of different thalli desynchronize under free running conditions. This might also be due to masking of the underlying circadian rhythms of photosynthesis by light-dark cycles. Finally, we used a pharmacological approach to identify that chloroplast translation might be necessary for clock control of light harvesting in M. polymorpha. We infer that the circadian regulation of photosynthesis are well-conserved amongst terrestrial plants.
Multidimensional cerebellar computations for flexible kinematic control of movements
Authors: Markanday Akshay , Hong Sungho , Inoue Junya , Schutter Erik De , Thier Peter
Published: January 2022

Both the environment and our body keep changing dynamically. Hence, ensuring movement precision requires adaptation to multiple demands occurring simultaneously. Here we show that the cerebellum performs the necessary multi-dimensional computations for the flexible control of different movement parameters depending on the prevailing context. This conclusion is based on the identification of a manifold-like activity in both mossy fibers (MF, network input) and Purkinje cells (PC, output), recorded from monkeys performing a saccade task. Unlike MFs, the properties of PC manifolds developed selective representations of individual movement parameters. Error feedback-driven climbing fiber input modulated the PC manifolds to predict specific, error type-dependent changes in subsequent actions. Furthermore, a feed-forward network model that simulated MF-to-PC transformations revealed that amplification and restructuring of the lesser variability in the MF activity is a pivotal circuit mechanism. Therefore, flexible control of movement by the cerebellum crucially depends on its capacity for multi-dimensional computations.
The phylogenomic landscape of the genus Serratia
Authors: Williams David J. , Grimont Patrick A. D. , Cazares Adrián , Grimont Francine , Ageron Elisabeth , Pettigrew Kerry A. , Cazares Daniel , Njamkepo Elisabeth , Weill François-Xavier , Heinz Eva , Holden Matthew T. G. , Thomson Nicholas R. , Coulthurst Sarah J.
Published: January 2022

The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We show that Serratia is a diverse genus which displays striking plasticity and ability to adapt to its environment, including a highly-varied portfolio of plasmids, and provide evidence of different patterns of gene flow across the genus. This work provides an essential platform for understanding the emergence of clinical and other lineages of Serratia.
OverFlap PCR – a reliable approach for generation of plasmid DNA libraries containing random sequences without template bias
Authors: Linars Artis , Silamikelis Ivars , Gudra Dita , Roga Ance , Fridmanis Davids
Published: January 2022

Over the decades the improvement of naturally occurring proteins and creation of novel ones has been the primary goal for many practical biotechnology researchers and it is widely recognized that randomization of protein sequences coupled to various effect screening methodologies is one of the most powerful techniques for fast, efficient and purposeful approach for acquisition of desired improvements. Over the years considerable advancements have been made in this field, however development of PCR based or template guided methodologies has been hampered by the resulting template sequence bias. In this article we present novel whole plasmid amplification based approach, which we named OverFlap PCR, for randomization of virtually any region of the plasmid DNA, without introduction of mentioned bias.
Consumer-driven nutrient recycling of freshwater decapods: linking ecological theories and application in integrated multi-trophic aquaculture
Authors: Musin Gabriela E. , Torres Maria Victoria , Carvalho Débora A.
Published: January 2022

Abstract

The Metabolic Theory of Ecology (MET) and the Ecological Stoichiometry Theory (EST) are central and complementary in the consumer-driven recycling conceptual basis. The comprehension of physiological processes of organisms at different levels of organizations is essential to explore and predict nutrient recycling behavior in different scenarios, and to design integrated productive systems that efficiently use the nutrient inputs through an adjusted mass balance. We fed with fish-feed three species of decapods from different families and with aquacultural potential to explore the animal-mediated nutrient dynamic and its applicability in productive systems. We tested whether physiological (body mass, body elemental content), ecological (diet), taxonomic and experimental (time of incubation) variables predicts N and P excretion rates and ratios across and within taxa. We also analysed body mass and body elemental content independently as predictors of N and P excretion of decapods across, among and within taxa. Finally, we verified if body content scales allometrically across and within taxa and if differed among taxa. Body mass and taxonomic identity predicted nutrient excretion rates both across and within taxa. When physiological variables were analysed independently, body size best predicted nutrient mineralization in both scales of analyses. Regarding body elemental content, only body P content scaled negatively with body mass across taxa. Results showed higher N-requirements and lower C:N of prawns than anomurans and crabs. The role of crustaceans as nutrient recyclers depends mainly on the species and body mass, and should be considered to select complementary species that efficiently use feed resources. Prawns need more protein in their feed and might be integrated with fish of higher N-requirements, while crabs and anomurans, with fish of lower N-requirements. Our study contributed to the background of MTE and EST through empirical data obtained from decapods and provided useful information to achieve more efficient aquaculture integration systems.
Paradigm shift in eukaryotic biocrystallization
Authors: Pilátová Jana , Pánek Tomáš , Oborník Miroslav , Čepička Ivan , Mojzeš Peter
Published: January 2022

Despite the widespread occurrence of crystalline inclusions in unicellular eukaryotes, scant attention has been paid to their composition, functions, and evolutionary origins, assuming just their inorganic contents. The advent of Raman microscopy, still scarcely used for biological samples, allowed chemical characterization of cellular inclusions in vivo. Using this method, herein we provide a substantial revision of the cellular crystalline inclusions across the broad diversity of eukaryotes examining all major supergroups. Surprisingly, here we show that 80 % of these crystalline inclusions contain purines, mostly anhydrous guanine (62 %), guanine monohydrate (2 %), uric acid (12 %) and xanthine (4 %). Hence, our findings indicate that purine biocrystallization is a very general and an ancestral eukaryotic process operating by an as-yet-unknown mechanism. Purine crystalline inclusions are high-capacity and rapid-turnover reserves of nitrogen of a great metabolic importance, as well as optically active elements, e.g., present in the light sensing eyespots of flagellates, possessing even more hypothetical functions. Thus, we anticipate our work to be a starting point for more in-depth studies of this phenomenon on the detailed level spanning from cell biology to global ecology, with further potential applications in biotechnologies, bio-optics or in human medicine.
Meiotic pairing and double strand break formation along the heteromorphic threespine stickleback sex chromosomes
Authors: Nath Shivangi , Welch Lucille A. , Flanagan Mary K. , White Michael A.
Published: January 2022

Double strand break repair during meiosis is normally achieved using the homologous chromosome as a repair template. Heteromorphic sex chromosomes have reduced sequence homology with one another, presenting unique challenges to the repair of double strand breaks. Our understanding of how heteromorphic sex chromosomes behave during meiosis has been largely limited to the ancient sex chromosomes of mammals, where the X and Y differ markedly in overall structure and gene content. Consequently, pairing of the X and Y chromosomes is limited to a small pseudoautosomal region. It remains unclear how more recently evolved sex chromosomes, that share considerably more sequence homology with one another, pair and repair double strand breaks during meiosis. One possibility is barriers to pairing evolve rapidly. Alternatively, recently evolved sex chromosomes may exhibit pairing and double strand break repair that more closely resembles that of their autosomal ancestors. Here we use the recently evolved X and Y chromosomes of the threespine stickleback fish (Gasterosteus aculeatus) to study patterns of pairing and double stranded break formation using molecular cytogenetics. We found that the sex chromosomes of threespine stickleback fish do not pair exclusively in the pseudoautosomal region. Instead, the chromosomes fully pair in a non-homologous fashion. To achieve this, the X chromosome underwent synaptic adjustment during pachytene to match the axis length of the Y chromosome. Double strand break formation and repair rate also matched that of the autosomes. Our results highlight that recently evolved sex chromosomes exhibit meiotic behavior that is reminiscent of autosomes and argues for further work to identify the homologous templates that are used to repair double strand breaks on the X and Y chromosomes.
The Antimicrobial Activity of Pechuel-Loeschea leubnitziae Leaf Extract and its Effect on The Expression Level of Methicillin Resistant Staphylococcus Aureus and Candida albicans Virulence-Associated Genes
Authors: Muhongo Mariah Ndilimeke , Kangogo Mourine , Bii Christine
Published: January 2022

The complete halt in the synthesis of new effective antimicrobial compounds is a global concern. Pathogenic microorganisms’ virulence mechanisms seem to have a significant impact on their pathogenesis. The purpose of this study was to examine the antimicrobial activity of the ethanol and methanol fractions of Pechuel-Loeschea leubnitziae leaf extract, as well as its effect on the expression level of virulence-associated genes.

The extract’s fractions were evaluated for antimicrobial activity against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Klebsiella pneumoniae (clinical), Methicillin-resistant Staphylococcus aureus, and Candida albicans ATCC 90029. The test organism’s antibiogram pattern was determined. The extracts’ attenuation effect on the target genes of the susceptible organisms was investigated employing relative quantification using RT-qPCR. The test organism’s antibiogram pattern revealed that it was drug-resistant, intermediate, and sensitive. The extracts tested positive for antimicrobial activity against Methicillin-resistant Staphylococcus aureus and Candida albicans ATCC 90029, with zones of inhibition varying from 20.33 to 29 mm. The lowest recorded MIC value was 4.688 mg/ml, while the highest was 37.5 mg/ml. In contrast to the methanol extract, the ethanol extract had a cidal action at a lower dose. The ethanol extract’s Sub-MIC (18.25 mg/ml) merely reduced the expression of the hly gene in MRSA. The MRSA virulence genes were not suppressed by the sub-MIC of methanol extract (18.25 mg/ml). Notably, the expression of als1, pbl1, and sap1 in Candida albicans ATCC 90029 was significantly attenuated when exposed to sub-MICs of ethanol extract (2,344 mg/ml) and methanol extract (9.375 mg/ml). Per the findings of this research, the leaves of P. leubnitziae could be a source of an effective antimicrobial agent in the therapy of MRSA/Candida-related disorders.
Skeletal muscle regeneration is altered in the R6/2 mouse model of Huntington’s disease
Authors: Hoque Sanzana , Sjögren Marie , Allamand Valérie , Gawlik Kinga , Franke Naomi , Durbeej Madeleine , Björkqvist Maria , Soylu-Kucharz Rana
Published: January 2022

Huntington’s disease (HD) is caused by CAG repeat expansion in the huntingtin (HTT) gene. Skeletal muscle wasting alongside central pathology is a well-recognized phenomenon seen in patients with HD and HD mouse models. HD muscle atrophy progresses with disease and affects prognosis and quality of life. Satellite cells, progenitors of mature skeletal muscle fibers, are essential for proliferation, differentiation, and repair of muscle tissue in response to muscle injury or exercise.

In this study, we aim to investigate the effect of mutant HTT on the differentiation and regeneration capacity of HD muscle by employing in vitro mononuclear skeletal muscle cell isolation and in vivo acute muscle damage model in R6/2 mice.

We found that, similar to R6/2 adult mice, neonatal R6/2 mice also exhibit a significant reduction in myofiber width and morphological changes in gastrocnemius and soleus muscles compared to WT mice. Cardiotoxin (CTX)-induced acute muscle damage in R6/2 and WT mice showed that the Pax7+ satellite cell pool was dampened in R6/2 mice at 4 weeks post-injection, and R6/2 mice exhibited an altered inflammatory profile in response to acute damage.

Our results suggest that, in addition to the mutant HTT degenerative effects in mature muscle fibers, expression of mutant HTT in satellite cells might alter developmental and regenerative processes to contribute to the progressive muscle mass loss in HD. Taken together, the results presented here encourage further studies evaluating the underlying mechanisms of satellite cell dysfunction in HD mouse models.
Pan-genomic analysis of transcriptional modules acrossSalmonellaTyphimurium reveals the regulatory landscape of different strains
Authors: Yuan Yuan , Seif Yara , Rychel Kevin , Yoo Reo , Chauhan Siddharth , Poudel Saugat , Al-bulushi Tahani , Palsson Bernhard O. , Sastry Anand
Published: January 2022

Salmonella entericaTyphimurium is a serious pathogen that is involved in human nontyphoidal infections. Tackling Typhimurium infections is difficult due to the species’ dynamic adaptation to its environment, which is dictated by a complex transcriptional regulatory network (TRN). While traditional biomolecular methods provide characterizations of specific regulators, it is laborious to construct the global TRN structure from this bottom-up approach. Here, we used a machine learning technique to understand the transcriptional signatures ofS. entericaTyphimurium from the top down, as a whole and in individual strains. Furthermore, we conducted cross-strain comparison of 6 strains in serovar Typhimurium to investigate similarities and differences in their TRNs with pan-genomic analysis. By decomposing all the publicly available RNA-Seq data of Typhimurium with independent component analysis (ICA), we obtained over 400 independently modulated sets of genes, called iModulons. Through analysis of these iModulons, we 1) discover three transport iModulons linked to antibiotic resistance, 2) describe concerted responses to cationic antimicrobial peptides (CAMPs), 3) uncover evidence towards new regulons, and 4) identify two iModulons linked to bile responses in strain ST4/74. We extend this analysis across the pan-genome to show that strain-specific iModulons 5) reveal different genetic signatures in pathogenicity islands that explain phenotypes and 6) capture the activity of different phages in the studied strains. Using all high-quality publicly-available RNA-Seq data to date, we present a comprehensive, data-driven Typhimurium TRN. It is conceivable that with more high-quality datasets from more strains, the approach used in this study will continue to guide our investigation in understanding the pan-transcriptome of Typhimurium. Interactive dashboards for all gene modules in this project are available athttps://imodulondb.org/under the “SalmonellaTyphimurium” page to enable browsing for interested researchers.
Canonical Wnt Signaling Induces Focal Adhesion and Integrin Beta-1 Endocytosis
Authors: Tejeda-Muñoz Nydia , Morselli Marco , Moriyama Yuki , Sheladiya Pooja , Pellegrini Matteo , De Robertis Edward M.
Published: January 2022

During canonical Wnt signaling, the Lrp6 and Frizzled co-receptors bind to the Wnt growth factor and the complex is endocytosed and sequestered together with Glycogen Synthase Kinase 3 (GSK3), Dishevelled (Dvl), and Axin inside the intraluminal vesicles of late endosomes, known as multivesicular bodies (MVBs). Here we present experiments showing that Wnt causes the endocytosis of focal adhesion (FA) proteins and depletion of Integrin β 1 (ITGβ1) from the cell surface. FAs and integrins link the cytoskeleton to the extracellular matrix. Wnt-induced endocytosis caused ITGβ1 depletion from the plasma membrane and was accompanied by striking changes in the actin cytoskeleton. In situ protease protection assays in cultured cells showed that ITGβ1 was sequestered within membrane-bounded organelles that corresponded to Wnt-induced MVBs containing GSK3 and FA-associated proteins. An in vivo model using Xenopus embryos dorsalized by Wnt8 mRNA showed that ITGβ1 depletion decreased Wnt signaling. The finding of a crosstalk between two mayor signaling pathways, canonical Wnt and focal adhesions, should be relevant to human cancer and cell biology.
Hemagglutinin stability determines influenza A virus susceptibility to a broad-spectrum fusion inhibitor Arbidol
Authors: Zhenyu Li , Tian Li , Meisui Liu , Tijana Ivanovic
Published: January 2022

Understanding mechanisms of resistance to antiviral inhibitors can reveal nuanced features of targeted viral mechanisms and, in turn, lead to improved strategies for inhibitor design. Arbidol is a broad-spectrum antiviral which binds to and prevents the fusion-associated conformational changes in the trimeric influenza hemagglutinin (HA). The rate-limiting step during HA-mediated membrane fusion is the release of the hydrophobic fusion peptides from a conserved pocket on HA. Here, we investigated how destabilizing or stabilizing mutations in or near the fusion peptide affect viral sensitivity to Arbidol. The degree of sensitivity was proportional to the extent of fusion peptide stability on the pre-fusion HA: stabilized mutants were more sensitive, and destabilized ones resistant to Arbidol. Single-virion membrane fusion experiments for representative Wild Type and mutant viruses demonstrated that resistance is a direct consequence of fusion-peptide destabilization not dependent on reduced Arbidol binding to HA at neutral pH. Our results support the model whereby the probability of individual HAs extending to engage the target membrane is determined by the composite of two critical forces: a ‘tug’ on the fusion peptide by the extension of the central coiled-coil on HA, and the key interactions stabilizing fusion peptide in the pre-fusion pocket. Arbidol increases the free-energy penalty for coiled-coil extension, but destabilizing mutations decrease the free-energy cost for fusion peptide release, accounting for the observed resistance. Our findings have broad implications for fusion-inhibitor design, viral mechanisms of resistance, and our basic understanding of HA-mediated membrane fusion.
Efficient enrichment of synchronized mouse spermatocytes suitable for genome-wide analysis
Authors: Carbajal Agustin , Gryniuk Irma , de Castro Rodrigo O. , Pezza Roberto J.
Published: January 2022

Chromatin-based mechanisms regulating developmental transitions during meiosis are fundamental but understudied aspects of male gametogenesis. Indeed, chromatin undergoes extensive remodeling during meiosis, leading to specific patterns of gene expression and chromosome organization, which ultimately controls fundamental meiotic processes such as recombination and homologous chromo-some associations. Recent game-changing advances have been made by analysis of chromatin binding sites of meiotic specific proteins genome-wide in mouse spermatocytes. However, further progress is still highly dependent on the reliable isolation of sufficient quantities of spermatocytes at specific stages of prophase I. Here, we describe a combination of methodologies adapted for rapid and reliable isolation of synchronized fixed mouse spermatocytes. We show that chromatin isolated from these cells can be used to study chromatin binding sites by ChIP-seq. High quality data we obtained from INO80 ChIP-seq in zygotene cells was used for functional analysis of chromatin binding sites.
cpSRP43 is both highly flexible and stable: Structural insights using a combined experimental and computational approach
Authors: Benton Mitchell , Furr Mercede , Kumar Vivek Govind , Gao Feng , Heyes Colin David , Suresh Kumar Thallapuranam Krishnaswamy , Moradi Mahmoud
Published: January 2022

The novel multidomain protein, cpSRP43, is a unique subunit of the post-translational chloroplast signal recognition particle (cpSRP) targeting pathway in higher plants. The cpSRP pathway is responsible for targeting and insertion of light-harvesting chlorophyll a/b binding proteins (LHCPs) to the thylakoid membrane. Nuclear-encoded LHCPs are synthesized in the cytoplasm then imported into the chloroplast. Upon emergence into the stroma, LHCPs form a soluble transit complex with the cpSRP heterodimer, which is composed of cpSRP43 and cpSRP54, a 54 kDa subunit homologous to the universally conserved GTPase in cytosolic SRP pathways. cpSRP43 is irreplaceable as a chaperone to LHCPs in their translocation to the thylakoid membrane and remarkable in its ability to dissolve aggregates of LHCPs without the need for external energy input. In previous studies, cpSRP43 has demonstrated significant flexibility and interdomain dynamics. However, the high flexibility and structural dynamics of cpSRP43 is yet unexplained by current crystal structures of cpSRP43. This is due, in part, to the fact that free full length cpSRP43 is so flexible that it is unable to crystalize. In this study, we explore the structural stability of cpSRP43 under different conditions using various biophysical techniques and find that this protein is concurrently highly stable and flexible. This conclusion is interesting considering that stable proteins typically possess a non-dynamic structure. Molecular dynamics (MD) simulations which correlated with data from biophysical experimentation were used to explain the basis of the extraordinary stability of cpSRP43. This combination of biophysical data and microsecond-level MD simulations allows us to obtain a detailed perspective of the conformational landscape of these proteins.
Application of the Logistic Model to the COVID-19 Pandemic in South Africa and the United States: Correlations and Predictions
Authors: Roberts David H.
Published: January 2022

We apply the logistic model to the four waves of COVID-19 taking place in South Africa over the period 3 January 2020 through 14 January 2022. We show that this model provides an excellent fit to the time history of three of the four waves. We then derive a theoretical correlation between the growth rate of each wave and its duration, and demonstrate that it is well obeyed by the South African data.

We then turn to the data for the United States. As shown by Roberts (2020a, 2020b), the logistic model provides only a marginal fit to the early data. Here we break the data into six “waves,” and treat each one separately. Five of the six can be analyzed, and we present full results. We then ask if these data provide a way to predict the length of the ongoing Omicron wave in the US (commonly called “wave 4,” but the sixth wave as we have broken the data up). Comparison of these data to those from South Africa, and internal evaluation of the US data, suggest that this current wave will peak about 18 January 2022, and will be substantially over by about 11 February 2022. The total number of infected persons by the time that the Omicron wave is completely over is projected be between 22 and 24 million.
Transgenerational transcriptional heterogeneity from cytoplasmic chromatin
Authors: Papathanasiou Stamatis , Mynhier Nikos A. , Liu Shiwei , Jacob Etai , Stokasimov Ema , van Steensel Bas , Zhang Cheng-Zhong , Pellman David
Published: January 2022

Transcriptional heterogeneity from plasticity of the epigenetic state of chromatin is thought to contribute to tumor evolution, metastasis, and drug resistance 1–3. However, the mechanisms leading to nongenetic cell-to-cell variation in gene expression remain poorly understood. Here we demonstrate that heritable transcriptional changes can result from the formation of micronuclei, aberrations of the nucleus that are common in cancer4,5. Micronuclei have fragile nuclear envelopes (NE) that are prone to spontaneous rupture, which exposes chromosomes to the cytoplasm and disrupts many nuclear activities 6,7. Using a combination of long-term live-cell imaging and same-cell, single-cell RNA sequencing (Look-Seq2), we identified significant reduction of gene expression in micronuclei, both before and after NE rupture. Furthermore, chromosomes in micronuclei fail to normally recover histone 3 lysine 27 acetylation, a critical step for the reestablishment of normal transcription after mitosis 8–10. These transcription and chromatin defects can persist into the next generation in a subset of cells, even after these chromosomes are incorporated into normal daughter nuclei. Moreover, persistent transcriptional repression is strongly associated with, and may be explained by, surprisingly long-lived DNA damage to these reincorporated chromosomes. Therefore, heritable alterations in transcription can originate from aberrations of nuclear architecture.
Human endothelial cells display a rapid and fluid flow dependent tensional stress increase in response to tumor necrosis factor-α
Authors: Brandt Matthias , Gerke Volker , Betz Timo
Published: January 2022

As endothelial cells form the inner layer of blood vessels they display the first barrier to interstitial tissues, which results in a crucial role for inflammation. On the global, systemic level an important element of the complex process controlling the inflammatory response is the release of the cytokine tumor necrosis factor-α (TNF-α). While other pro-inflammatory agents like thrombin or histamine are known to induce acute but transient changes in endothelial cells which have been well studied biologically as well as mechanically, TNF-α is primarily known for its sustained effects on permeability and leukocyte recruitment. These functions are associated with transcriptional changes that take place on the timescale of hours and days. Here we show that already 4 minutes after the addition of TNF-α onto monolayers of human umbilical vein endothelial cells, a striking rise in mechanical substrate traction force and internal monolayer tension can be recorded. As expected, the traction forces act primarily at the boundary of the monolayer. While the traction forces increase monotonically during the initial cellular response, we find that the internal monolayer tension displays a rapid peak that can be abolished when applying a shear flow to the cells. The increased internal monolayer tension may provide a mechanical signal for the cells to prepare for the recruitment of leukocytes, additionally to the well studied biochemical response.
Enhanced food motivation in obese mice is controlled by D1R expressing spiny projection neurons in the nucleus accumbens
Authors: Matikainen-Ankney Bridget A , Legaria Alex A , Vachez Yvan M , Murphy Caitlin A , Pan Yiyan , Schaefer Robert F , McGrath Quinlan J , Wang Justin G , Bluitt Maya N , Norris Aaron J , Creed Meaghan C , Kravitz Alexxai V
Published: January 2022

Obesity is a chronic relapsing disorder that is caused by an excess of caloric intake relative to energy expenditure. In addition to homeostatic feeding mechanisms, there is growing recognition of the involvement of food reward and motivation in the development of obesity. However, it remains unclear how brain circuits that control food reward and motivation are altered in obese animals. Here, we tested the hypothesis that signaling through pro-motivational circuits in the core of the nucleus accumbens (NAc) is enhanced in the obese state, leading to invigoration of food seeking. Using a novel behavioral assay that quantifies physical work during food seeking, we confirmed that obese mice work harder than lean mice to obtain food, consistent with an increase in the relative reinforcing value of food in the obese state. To explain this behavioral finding, we recorded neural activity in the NAc core with bothin vivoelectrophysiology and cell-type specific calcium fiber photometry. Here we observed greater activation of D1-receptor expressing NAc spiny projection neurons (NAc D1SPNs) during food seeking in obese mice relative to lean mice. Withex vivoslice physiology we identified both pre- and post-synaptic mechanisms that contribute to this enhancement in NAc D1SPNactivity in obese mice. Finally, blocking synaptic transmission from D1SPNsdecreased physical work during food seeking and attenuated high-fat diet-induced weight gain. These experiments demonstrate that obesity is associated with a selective increase in the activity of D1SPNsduring food seeking, which enhances the vigor of food seeking. This work also establishes the necessity of D1SPNsin the development of diet-induced obesity, establishing these neurons as a potential therapeutic target for preventing obesity.
An industrial intelligent grasping system based on convolutional neural network
Authors: Daqi Jiang , Hong Wang , Bin Zhou , Chunfeng Wei
Published: January 2022

Purpose

This paper aims to save time spent on manufacturing the data set and make the intelligent grasping system easy to deploy into a practical industrial environment. Due to the accuracy and robustness of the convolutional neural network, the success rate of the gripping operation reached a high level.

Design/Methodology/Approach

The proposed system comprises two diverse kinds of convolutional neuron network (CNN) algorithms used in different stages and a binocular eye-in-hand system on the end effector, which detects the position and orientation of workpiece. Both algorithms are trained by the data sets containing images and annotations, which are generated automatically by the proposed method.

Findings

The approach can be successfully applied to standard position-controlled robots common in the industry. The algorithm performs excellently in terms of elapsed time. Procession of a 256 × 256 image spends less than 0.1 s without relying on high-performance GPUs. The approach is validated in a series of grasping experiments. This method frees workers from monotonous work and improves factory productivity.

Originality/Value

The authors propose a novel neural network whose performance is tested to be excellent. Moreover, experimental results demonstrate that the proposed second level is extraordinary robust subject to environmental variations. The data sets are generated automatically which saves time spent on manufacturing the data set and makes the intelligent grasping system easy to deploy into a practical industrial environment. Due to the accuracy and robustness of the convolutional neural network, the success rate of the gripping operation reached a high level.
Beginning farmer and rancher credit usage by socially disadvantaged status
Authors: Ahrendsen Bruce L. , Dodson Charles B. , Short Gianna , Rainey Ronald L. , Snell Heather A.
Published: January 2022

Purpose

The purpose of this paper is to examine credit usage by beginning farmers and ranchers (BFR). BFR credit usage is stratified by location (state) and by socially disadvantaged farmer and rancher (SDFR, also known as historically underserved) status. SDFR groups are defined to include women; individuals with Hispanic, Latino or Spanish Origin; individuals who identify as American Indian or Alaskan Native, Black or African American, Asian, Native Hawaiian or other Pacific Islander. Non-SDFR is defined as individuals who identify as non-Hispanic, White men.

Design/methodology/approach

The US Department of Agriculture’s Census of Agriculture, Agricultural Resource Management Survey (ARMS) is linked with Farm Service Agency (FSA) loan program administrative data to estimate shares of BFR operations using FSA credit. Census data provided information on population changes in total farms and BFR operations from 2012 to 2017 which are compared by SDFR status.

Findings

Results reveal differences among BFR operations active in agricultural credit markets by SDFR status and state. BFR were more common among SDFR groups as well as in regions where farms tend to be smaller, such as the Northeast, compared to a more highly agricultural upper Midwest. Among BFR, non-SDFR are more likely to utilize credit than SDFR, however, FSA appeared to be crucial in enabling BFR and especially beginning SDFR groups to access loans.

Originality/value

The results are timely and of keen interest to researchers, industry and policymakers and are expected to assist in developing and adjusting policies to effectively promote and improve BFR success in general and for beginning SDFR groups.
Evaluating the legibility of urban parks based on neuroscience and the FVFL model
Authors: Gholami Yasaman , Taghvaei Seyed Hassan , Norouzian-Maleki Saeid , Mansouri Sepehr Rouhollah
Published: January 2022

Purpose

The purpose of the study is to quantitatively evaluate the role of landscape values and factors in urban parks experimentally based on neuroscience.

Design/methodology/approach

In the first step, ten major parks were selected out of 59 regional and trans-regional parks in Tehran for field study analysis. Next, considering the diversity and abundance of landscape elements in the selected parks, Mellat Park was chosen for the case study.

Findings

The fixation duration of the factors has an average correlation coefficient of 0.5865, −0.5035 and −0.5125 for the overall sketch map, quality and accuracy, respectively. The results indicated that the “quality of people's cognitive maps” has a direct relation to fixation duration on “human-made factors” and an inverse relation to fixation duration on “natural factors” and “human activities and behavioral factors” in the park.

Practical implications

The results can pave the way for further research in the interdisciplinary fields of landscape architecture and neuroscience.

Originality/value

Legibility is a superior quality of urban spaces that profoundly affect how people perceive and behave.
Interpretive structural model of trust factors in construction virtual project teams
Authors: Sagar Sukhwant Kaur , Oladinrin Olugbenga Timo , Arif Mohammed , Rana Muhammad Qasim
Published: January 2022

Purpose

Organisational dependence on virtual project teams (VPTs) is growing dramatically due to the substantial benefits they offer, such as efficiently achieving objectives and improving organisational performance. One of the major issues that influence the effectiveness of VPTs is trust building. This study aims to determine the key factors of trust in VPTs and design a model by identifying the interrelationships among the trust factors.

Design/methodology/approach

Focus group discussion was used to gather data on factors affecting trust in VPTs and their interrelationships. Interpretive structural modelling (ISM) was used to establish the relationship among the factors. Cross-impact matrix multiplication applied to classification analysis was conducted to identify the driving power and the dependence power towards effective VPTs in the construction sector.

Findings

The finding revealed that “characteristics of team members” (such as ability, integrity, benevolence, competence, reliability and professionalism) is the most significant factor for building trust in virtual team members. Some factors were further identified as having high driving power, while others were defined as having high dependence variables.

Practical implications

The findings will assist construction managers and practitioners dealing with VPTs identify the factors influencing trust among team members. Taking cognisance of the factors that influence trust will enable them to design more effective virtual team arrangements.

Originality/value

As the first research of its kind using ISM technique, the study offers insights into interrelationships between trust factors in the construction VPTs. It provides guides for construction managers on the effective management of trustworthy VPTs.
Evaluating the climate-responsive design strategies of vernacular buildings in Konearirajapuram village, Nagappattinam, India
Authors: Purushothaman A. Purushothaman A. , Thirumaran K. Thirumaran K.
Published: January 2022

Purpose

Vernacular architecture is an architectural style of buildings that were constructed by artisanal builders who lacked formal qualifications, used local materials and had a deep understanding of local climatic needs. This approach addressed climatic, energy, materials and construction issues in a low-cost way. Building interiors were often made comfortable by using passive internal climate regulation methods, which could be key to resolving some of the current issues of the modern world.

Design/methodology/approach

Tamil Nadu is a land full of local architecture, with Konearirajapuram settlement a thriving specimen of its vernacular architecture, as one of the original Vathima villages (planned Brahmin villages). Here the authors present an appraisal of this settlement's native architecture with its various passive design elements. A questionnaire survey was also conducted among local residents, living in both vernacular and contemporary residential buildings, to understand the quality of indoor environmental comfort in the different building types (single courtyard, multiple courtyards and multiple story houses with courtyards).

Findings

The results of this study show that energy-efficient bioclimatic design strategies of traditional buildings can be analyzed with the help of climatic data and analysis tools such as Mahoney tables and Olgyay's bioclimatic chart. The study shows that vernacular design techniques and principles conserve more energy than modern buildings. The findings suggest that practical solutions for improving contemporary residential developments can be found in traditional architectural approaches and that these approaches should be incorporated in new developments to achieve energy efficiency and a sustainable future.

Research limitations/implications

A detailed survey and the user preferences are plotted in detail in this paper; similarly, Mahoney table and its requirements are analyzed with respect to context; and the results are elaborated and justified.

Originality/value

This study analyzes an entire settlement of Konearirajapuram with 300 units of vernacular residences high in comfort even at extreme climates. Assessment is carried in both qualitative case and quantitative case. Even though there are no previous studies analyzed to identify the effectiveness of the artisanal builders of bioclimatic architecture. Hence, this study brings out the solution for current energy problems from the traditional settings, because the traditional buildings requires no active systems for indoor comfort except a fan, which is negligible in terms of energy use.
The challenges of empowering waqf land in Indonesia: an analytical network process analysis
Authors: Fauzi R.M. Qudsi , Hapsari Meri Indri , Herianingrum Sri , Fanani Sunan , Kurnia Tuti
Published: January 2022

Purpose

This paper aims to identify the factors that hinder the successful empowerment of waqf land in Indonesia empirically by applying the analytic networking process (ANP).

Design/methodology/approach

In this study, after the waqf land problem criteria were introduced, an ANP model was developed and applied to identify the main problem, solution and strategy as a framework to guide stakeholders to produce policy recommendations appropriately and optimally.

Findings

The results showed that the main priority of the problem is the nadzir aspect. Furthermore, each criterion’s problems are a low public trust, unprofessional nadzir (waqf manager), a huge number of idle waqf lands, the absence of waqf certificates and non-economic waqf lands utilisation. Meanwhile, the main priorities for each aspect of the solution are socialisation and education to the community, nadzir certification, utilisation of information technology for the administration of waqf land governance, waqf land certification and innovation of waqf land development projects. Then, the long-term strategic priority is optimising the community’s role in the empowerment of waqf land.

Research limitations/implications

The development of the ANP model would give the institutions a modest, flexible and convenient approach to evaluate the barriers present in waqf land. However, ANP requires greater effort because it is a highly complex methodology that compels a study to use more numerical calculations in assessing composite priorities.

Originality/value

Not many studies on waqf land issues in Indonesia have been discussed empirically. Most of these studies are in the form of descriptive studies. This study introduces the ANP approach to illustrate the main problems of waqf land empowerment in Indonesia. ANP is a new approach to the decision-making process through a process that produces a general framework for treating decisions without making assumptions regarding independence between elements.