bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural Networks for self-adjusting Mutation Rate Estimation when the Recombination Rate is unknown
Authors: Burger Klara Elisabeth , Pfaffelhuber Peter , Baumdicker Franz
Published: September 2021

Estimating the mutation rate, or equivalently effective population size, is a common task in population genetics. If recombination is low or high, optimal linear estimation methods are known and well understood. For intermediate recombination rates, the calculation of optimal estimators is more challenging. As an alternative to model-based estimation, neural networks and other machine learning tools could help to develop good estimators in these involved scenarios. However, if no benchmark is available it is difficult to assess how well suited these tools are for different applications in population genetics.

Here we investigate feedforward neural networks for the estimation of the mutation rate based on the site frequency spectrum and compare their performance with model-based estimators. For this we use the model-based estimators introduced by Fu, Futschik et al., and Watterson that minimize the variance or mean square error for no and free recombination. We find that neural networks reproduce these estimators if provided with the appropriate features and training sets. Remarkably, using the model-based estimators to adjust the weights of the training data, only one hidden layer is necessary to obtain a single estimator that performs almost as well as model-based estimators for low and high recombination rates, and at the same time provides a superior estimation method for intermediate recombination rates. We apply the method to simulated data based on the human chromosome 2 recombination map, highlighting its robustness in a realistic setting where local recombination rates vary and/or are unknown.
How important are functional and developmental constraints on phenotypic evolution? An empirical test with the stomatal anatomy of flowering plants
Authors: Muir Christopher D. , Conesa Miquel Àngel , Galmés Jeroni , Pathare Varsha S. , Rivera Patricia , Rodríguez Rosana López , Terrazas Teresa , Xiong Dongliang
Published: September 2021

Functional and developmental constraints on phenotypic variation may cause traits to covary over millions of years and slow populations from reaching their adaptive optima. Alternatively, trait covariation may result from selective constraint if some trait combinations are generally maladaptive. Quantifying the relative contribution of functional, developmental, and selective constraints on phenotypic variation is a longstanding goal of macroevolution, but it is often difficult to distinguish different types of constraints. The anatomy of leaves with stomata on both surfaces (amphistomatous) present a unique opportunity to test the importance of functional and developmental constraints on phenotypyic evolution. The key insight is that stomata on each leaf surface encounter the same functional and developmental constraints, but potentially different selective constraints because of leaf asymmetry in light capture, gas exchange, and other features. Independent evolution of stomatal traits on each surface imply that functional and developmental constraints alone likely do not explain trait covariance. Packing limits on how many stomata can fit into a finite epidermis and cell-size-mediated developmental integration are hypothesized to constrain variation in stomatal anatomy. The simple geometry of the planar leaf surface and knowledge of stomatal development make it possible to derive equations for phenotypic (co)variance caused by these constraints and compare them with data. We analyzed evolutionary covariance between stomatal density and length in amphistomatous leaves from 236 phylogenetically independent contrasts using a robust Bayesian model. Stomatal anatomy on each surface diverges partially independently, meaning that packing limits and developmental integration are not sufficient to explain phenotypic (co)variation. Hence, selective constraints, which require an adaptive explanation, likely contribute to (co)variation in ecologically important traits like stomata. We show how it is possible to evaluate the contribution of different constraints by deriving expected patterns of (co)variance and testing them using similar but separate tissues, organs, or sexes.
A molecular docking study of human STEAP2 for the discovery of new potential anti-prostate cancer chemotherapeutic candidates
Authors: Ongaba Timothy , Ndekezi Christian , Nakiddu Nana Jaqueline
Published: September 2021

Prostate cancer refers to uncontrolled abnormal cell growth (Cancer) within the prostate gland. The disease is a rising health concern and accounts for 3.8% of all cancer deaths globally. Uganda has one of the highest incidence rates of the disease in Africa being 5.2% and many of the diagnosed patients are found to have advanced stage prostate cancer. This study aimed to use STEAP2 protein (prostate cancer specific biomarker) for the discovery of new lead compounds against prostate cancer.

To determine the most likely compound that can bind to STEAP2 protein, we docked the modelled STEAP2 3 Dimension structure against 2466 FDA (Food and Drug Administration) approved drug candidates using Autodock vina. Protein Basic Local Alignment Search Tool (BLASTp) search, Multiple Sequence Alignment (MSA), and phylogenetics were further carried out to analyse the diversity of this marker and determine its conserved domains as suitable target regions.

Six promising drug candidates (ligands) were identified of which Triptorelin had the highest binding energy (-12.1 kcal/mol). Leuprolide was the second most promising candidate with a docking energy of -11.2 kcal/mol. All the top 3 of 6 drugs interacted with highly conserved residues Ser-372 and Gly-369 in close proximity with the iron binding domain that was shown to be important for catalysis of metal reduction.

The two drugs had earlier been approved for treatment of advanced prostate cancer but with an elusive mode of action. Thanks to this study we now have an insight on how their interaction with STEAP2 might be important during treatment.

Author summary

Previous studies on prostate cancer prevalence have shown that Uganda among other low to middle income countries has a high prostate cancer incidence rate. Majority of the patients at the time of diagnosis have advanced stage disease. While there has been great improvement in therapeutic options for prostate cancer over the last decade, the drugs currently used are still limited and not 100% effective making cure elusive. This is further compounded by undesirable side-effects from some of the treatments. Altogether this creates a need for the discovery of novel, safe, and efficacious chemotherapeutic agents with minimal or no side effects. In this study, we used a prostate cancer specific protein biomarker; STEAP2 that is highly expressed at all disease stages and is androgen independent and FDA approved drugs from the drugbank to help improve drug specificity, efficacy, and reduce undesirable side effects throughin-silicomethods. The results from the study give an insight on mechanisms of action of current therapy for advanced disease and suggest these very drugs be used even at early stage disease.
MrParse: Finding homologues in the PDB and the EBI AlphaFold database for Molecular Replacement and more
Authors: Simpkin Adam J. , Thomas Jens M. H. , Keegan Ronan M. , Rigden Daniel J.
Published: September 2021

Crystallographers have an array of search model options for structure solution by Molecular Replacement (MR). Well-established options of homologous experimental structures and regular secondary structure elements or motifs are increasingly supplemented by computational modelling. Such modelling may be carried out locally or use pre-calculated predictions retrieved from databases such as the EBI AlphaFold database. MrParse is a new pipeline to help streamline the decision process in MR by consolidating bioinformatic predictions in one place. When reflection data are provided, MrParse can rank any homologues found using eLLG which indicates the likelihood that a given search model will work in MR. In-built displays of predicted secondary structure, coiled-coil and transmembrane regions further inform the choice of MR protocol. MrParse can also identify and rank homologues in the EBI AlphaFold database, a function that will also interest other structural biologists and bioinformaticians.
Clinically Relevant Mathematical Model for the BCG-based Treatment Of Type 1 Diabetes
Authors: Lazebnik Teddy , Bunimovich-Mendrazitsky Svetlana , Kiselyov Alex
Published: September 2021

This work introduces a model of immunotherapy treatment, namely the Bacillus Calmette-Guerin (BCG) vaccine, of type 1 diabetes (T1D). The model takes into consideration a clinically relevant interaction network between multiple immune cells and compartments. A set of ordinary differential equations (ODEs) is introduced to capture the connectivity between these variables and clinical presentation of the disease. Four subsets of the T1D patients and healthy controls that exhibit normal and high-level glucose consumption are evaluated. The results that obtained for mice, suggest that BCG treatment of the T1D patients that follow healthy eating habits normalizes glucose to levels observed in non-diabetic controls. Furthermore, glucose consumption profoundly influences disease progression. The stable equilibrium state with constant glucose levels is not attainable without repeated BCG treatment. This outcome suggests that immunotherapy may modulate molecular and cellular manifestations of the disease but it does not eliminate T1D. Of note, our data indicate that the BCG immunotherapy treatment may benefit healthy controls on a high-glucose diet. One may speculate the preventive BCG treatment to provide long-term health benefits in this specific cohort.

Author summary

We proposed a clinically relevant mathematical model of Bacillus Calmette-Guerin (BCG) based immunotherapy for type 1 diabetes (T1D) treatment. The model shows that BCG treatment is able to delay the T1D effects and to provide long-term health benefits while it may modulate molecular and cellular manifestations of the disease but it does not eliminate T1D. The main advantage of the proposed model is the ability to personalize the treatment protocol according to the patient’s metabolism and diet.
The Chromatin Remodeling Protein CHD-1 and the EFL-1/DPL-1 Transcription Factor Cooperatively Down Regulate CDK-2 to Control SAS-6 Levels and Centriole Number
Authors: Iyer Jyoti , Gentry Lindsey , Bergwell Mary , Smith Amy , Guargliardo Sarah , Kropp Peter A. , Sankaralingam Prabhu , Liu Yan , Spooner Eric , Bowerman Bruce , O’Connell Kevin F.
Published: September 2021

Centrioles are submicron-scale, barrel-shaped organelles typically found in pairs, and play important roles in ciliogenesis and bipolar spindle assembly. In general, successful execution of centriole-dependent processes is highly reliant on the ability of the cell to stringently control centriole number. This in turn is mainly achieved through the precise duplication of centrioles during each S phase. Aberrations in centriole duplication disrupt spindle assembly and cilia based signaling and have been linked to cancer, primary microcephaly and a variety of growth disorders. Studies aimed at understanding how centriole duplication is controlled have mainly focused on the post-translational regulation of two key components of this pathway: the master regulatory kinase ZYG-1/Plk4 and the scaffold component SAS-6. In contrast, how transcriptional control mechanisms might contribute to this process have not been well explored. Here we show that the chromatin remodeling protein CHD-1 contributes to the regulation of centriole duplication in the C. elegans embryo. Specifically, we find that loss of CHD-1 or inactivation of its ATPase activity can restore embryonic viability and centriole duplication to a strain expressing insufficient ZYG-1 activity. Interestingly, loss of CHD-1 is associated with increases in the levels of two ZYG-1-binding partners: SPD-2, the centriole receptor for ZYG-1 and SAS-6. Finally, we explore transcriptional regulatory networks governing centriole duplication and find that CHD-1 and a second transcription factor, EFL-1/DPL-1 cooperate to down regulate expression of CDK-2, which in turn promotes SAS-6 protein levels. Disruption of this regulatory network results in the overexpression of SAS-6 and the production of extra centrioles.

Author Summary

Centrioles are cellular constituents that play an important role in cell reproduction, signaling and movement. To properly function, centrioles must be present in the cell at precise numbers. Errors in maintaining centriole number result in cell division defects and diseases such as cancer and microcephaly. How the cell maintains proper centriole copy number is not entirely understood. Here we show that two transcription factors, EFL-1/DPL-1 and CHD-1 cooperate to reduce expression of CDK-2, a master regulator of the cell cycle. We find that CDK-2 in turn promotes expression of SAS-6, a major building block of centrioles. When EFL-1/DPL-1 and CHD-1 are inhibited, CDK-2 is overexpressed. This leads to increased levels of SAS-6 and excess centrioles. Our work thus demonstrates a novel mechanism for controlling centriole number and is thus relevant to those human diseases caused by defects in centriole copy number control.
Concomitant Pyroptotic and Apoptotic Cell Death Triggered in Monocytes Infected by Zika Virus
Authors: Wen Chunxia , Yu Yufeng , Gao Chengfeng , Qi Xian , Cardona Carol J. , Xing Zheng
Published: September 2021

Zika virus (ZIKV) is a positive-sense RNA flavivirus and can cause serious neurological disorders including microcephaly in infected fetus. As a mosquito-borne arbovirus, ZIKV enters bloodstream and is transmitted into the fetus through the placenta in pregnant women. Monocytes are considered one of the earliest blood cell types to be infected by ZIKV. As a first line defence, monocytes are crucial components in innate immunity and host responses and may impact viral pathogenesis in humans. Previous studies have shown that ZIKV infection can activate inflammasomes and induce proinflammatory cytokines in monocytes. In this report, we showed that ZIKV carried out a productive infection, which lead to cell death in human and murine monocytic cells. In addition to the presence of cleaved caspase-3, indicating that apoptosis was involved, we identified the cleaved caspase-1 and gasdemin D (GSDMD) as well as increased secretion of IL-1β and IL-18, suggesting that the inflammasome was activated that may lead to pyroptosis in infected monocytes. The pyroptosis was NLRP3-dependent and could be suppressed in the monocytes treated with shRNA to target and knockdown caspase-1, or an inhibited for caspase-1, indicating that the pyroptosis was triggered via a canonical approach. Our findings in this study demonstrate a concomitant occurrence of apoptosis and pyroptosis in ZIKV-infected monocytes, with multiple mechanisms involved in the cell death, which may have potentially significant impacts on viral pathogenesis in humans.
WolbachiastrainwAu differs in cellular perturbation and virus inhibition profiles from previously characterisedWolbachiastrains
Authors: Rainey Stephanie M , Geoghegan Vincent , Lefteri Daniella A , Ant Thomas H , Martinez Julien , McNamara Cameron , Sinkins Steven P
Published: September 2021

Some strains of the inherited bacteriumWolbachiahave been shown to be effective at reducing the transmission of dengue and other positive-sense RNA viruses byAedes aegyptiin both laboratory and field settings and are being deployed for dengue control. The degree of virus inhibition varies betweenWolbachiastrains; density and tissue tropism can contribute to these differences but there are also indications that this is not the only factor involved: for example, strainswAu andwAlbA are maintained at similar densities but onlywAu produces strong dengue inhibition. We previously reported perturbations in lipid transport dynamics, including sequestration of cholesterol in lipid droplets, with strainswMel /wMelPop inAe.aegypti. Here we show that strainwAu does not produce the same cholesterol sequestration phenotype despite displaying strong virus inhibition and moreover, in contrast towMel,wAu antiviral activity was not rescued by cyclodextrin treatment. To further investigate the cellular basis underlying these differences, proteomic analysis of midguts was carried out onAe.aegyptilines and revealed thatwAu-carrying midguts showed a distinct proteome when compared toWolbachia-free,wMel- orwAlbA-carrying midguts, in particular with respect to lipid transport and metabolism. The data suggest a possible role for perturbed RNA processing pathways inwAu virus inhibition. Together these results indicate thatwAu shows unique features in its inhibition of arboviruses compared to previously characterizedWolbachiastrains.

Author Summary

Wolbachiaendosymbionts can block transmission of dengue virus byAedes aegyptimosquitoes, andWolbachiarelease programs for dengue control are now being undertaken in several countries. Understanding the mechanisms ofWolbachia-mediated antiviral activity is important for maximizing the efficacy of this control approach. Using functional and proteomic analyses, this study indicates that different strains ofWolbachiaperturb cellular functions in diverse ways and display different antiviral profiles. These differences raise the possibility thatWolbachiastrain switching could be used to counteract viral escape mutations, should they arise and threaten the efficacy of dengue control programmes.
High lineage survivorship across the end-Devonian Mass Extinction suggested by a remarkable new Late Devonian actinopterygian
Authors: Giles Sam , Feilich Kara , Warnock Rachel , Pierce Stephanie E. , Friedman Matt
Published: September 2021

A mass extinction at the end of the Devonian is thought to have had a major influence on the evolution of actinopterygians (ray-finned fishes), which comprise half of living vertebrates. This extinction appears to have acted as a bottleneck, paring the early diversity of the group to a handful of survivors. Coupled with increases in taxonomic and morphological diversity in the Carboniferous, this contributes to a model of explosive post-extinction radiation. However, most actinopterygians from within a ~20-million-year (Myr) window surrounding the extinction remain poorly known, contributing to uncertainty about these patterns. An exceptionally preserved fossil of a diminutive fish from 7 Myr before the extinction reveals unexpected anatomical features that suggest a very different story. This new fossil nests within a clade of post-Devonian species and, in an expanded phylogenetic analysis, draws multiple lineages of Carboniferous actinopterygians into the Devonian. This suggests cryptic but extensive lineage diversification in the latest Devonian, followed by more conspicuous feeding and locomotor structure diversification in the Carboniferous. Our revised model matches more complex patterns of divergence, survival, and diversification around the Devonian-Carboniferous boundary in other vertebrate clades. It also fundamentally recalibrates the onset of diversification early in the history of this major radiation.
ERM-1 phosphorylation and NRFL-1 redundantly control lumen formation in the C. elegans intestine
Authors: Sepers Jorian J. , Ramalho João J. , Kroll Jason R. , Schmidt Ruben , Boxem Mike
Published: September 2021

Reorganization of the plasma membrane and underlying actin cytoskeleton into specialized domains is essential for the functioning of most polarized cells in animals. Proteins of the ezrin-radixin-moesin (ERM) and Na+/H+ exchanger 3 regulating factor (NHERF) family are conserved regulators of cortical specialization. ERM proteins function as membrane-actin linkers and as molecular scaffolds that organize the distribution of proteins at the membrane. NHERF proteins are PDZ-domain containing adapters that can bind to ERM proteins and extend their scaffolding capability. Here, we investigate how ERM and NHERF proteins function in regulating intestinal lumen formation in the nematode Caenorhabditis elegans. C. elegans has single ERM and NHERF family proteins, termed ERM-1 and NRFL-1, and ERM-1 was previously shown to be critical for intestinal lumen formation. Using CRISPR/Cas9-generated nrfl-1 alleles we demonstrate that NRFL-1 localizes at the intestinal microvilli, and that this localization is depended on an interaction with ERM-1. However, nrfl-1 loss of function mutants are viable and do not show defect in intestinal development. Interestingly, combining nrfl-1 loss with erm-1 mutants that either block or mimic phosphorylation of a regulatory C-terminal threonine causes severe defects in intestinal lumen formation. These defects are not observed in the phosphorylation mutants alone, and resemble the effects of strong erm-1 loss of function. The loss of NRFL-1 did not affect the localization or activity of ERM-1. Together, these data indicate that ERM-1 and NRFL-1 function together in intestinal lumen formation in C. elegans. We postulate that the functioning of ERM-1 in this tissue involves actin-binding activities that are regulated by the C-terminal threonine residue and the organization of apical domain composition through NRFL-1.
Two Ubiquitin-Activating Systems Occur in Plants with One Playing a Major Role in Plant Immunity
Authors: Zhou Bangjun , Wang Chaofeng , Chen Xuanyang , Zhang Yi , Zeng Lirong
Published: September 2021

Many plants possess two or more ubiquitin-activating enzymes (E1). However, it is unclear whether the E1s of a plant genome play equivalent roles in various pathways. Here we report that tomato and tobacco encode dual ubiquitin-activating systems (DUAS) in which the E1s UBA1 and UBA2 display differential specificities in charging four groups of E2s. The C-terminal ubiquitin-folding domain of the E1s play a major but not sole role in determining the differential specificities of charging the four groups E2s. The dual systems do not play equivalent roles in plant immunity, with silence of UBA2 only compromising host immunity. Among the differentially charged E2s, group IV members UBC32, UBC33 and UBC34 are shown to be essential for ER-associated protein degradation (ERAD) and plant immunity. Like tomato, Arabidopsis UBC32/33/34 E2 triplet are also differentially charged by its E1s and are essential for plant immunity. Loss of function in Arabidopsis UBC32, UBC33 and UBC34 does not affect flg22 and elf18-triggered inhibition of seedling growth but results in alteration of ER stress tolerance, which likely contribute to the diminished plant immunity in the mutants. Our results uncover DUAS in plants and a previously unknown E1–ERAD-associated E2 triplet module in the regulation of host immunity.

One sentence summary

Plant dual ubiquitin E1 systems play distinct roles in plant immunity by differentially charging the ERAD-associated E2s for ER stress tolerance.
Coding of social odors in the hippocampal CA2 region as a substrate for social memory
Authors: Hassan Sami I. , Bigler Shivani , Siegelbaum Steven A.
Published: September 2021

The ability to encode and update information about individuals is critical for lasting social relationships. Although the hippocampus is important for social recognition memory, its underlying neural representations remain elusive. Here we investigate the neural codes mediating social recognition and learning by examining social odor recognition and associative odor-reward learning in mice. We performed high-resolution calcium imaging from the hippocampal CA2 region of awake head-fixed mice, as CA2 is necessary for social recognition memory. We find that CA2 encodes specific neural representations of novel social odors that are further refined during associative odor-reward learning. Optogenetic silencing of CA2 impairs the formation of reward associations. Furthermore, CA2 population activity represents odors in a geometry that enables abstract representations of social versus non-social odors. Thus, CA2 distinguishes multiple forms of olfactory stimuli to enhance the learning of social odors and associations, which are poised to serve as substrates of social memory.
Changes in antennal gene expression underlying sensory system maturation in Rhodnius prolixus
Authors: Latorre-Estivalis Jose Manuel , Große-Wilde Ewald , da Rocha Fernandes Gabriel , Hansson Bill S. , Lorenzo Marcelo Gustavo
Published: September 2021

Background

Triatomine bugs are the blood feeding insect vectors transmitting Chagas disease to humans, a neglected tropical disease that affects over 8 million people, mainly in Latin America. The behavioral responses to host cues and bug signals in Rhodnius prolixus are state dependent, i.e., they vary as a function of post-ecdysis age. At the molecular level, these changes in behavior are probably due to a modulation of peripheral and central processes. In the present study, we report a significant modulation of the expression of a large set of sensory-related genes. Results were generated by means of antennal transcriptomes of 5th instar larvae along the first week (days 0, 2, 4, 6 and 8) after ecdysis sequenced using the Illumina platform.

Results

Age induced significant changes in transcript abundance were established in more than 6,120 genes (54,7 % of 11,186 genes expressed) in the R. prolixus antenna. This was especially true between the first two days after ecdysis when more than 2,500 genes had their expression significantly altered. In contrast, expression profiles were almost identical between day 6 and 8, with only a few genes showing significant modulation of their expression. A total of 86 sensory receptors, odorant carriers and odorant degrading enzymes were significantly modulated across age points and clustered into three distinct expression profiles.

Conclusions

The set of sensory genes whose expression increased with age (profile 3) may include candidates underlying the increased responsiveness to host cues shown by R. prolixus during the first days after molting. For the first time, we describe the maturation process undergone at the molecular level by the peripheral sensory system is described in an hemimetabolous insect.
Green synthesis of silver nanoparticles using psychrotolerant strains of Tulasnella albida from South Orkney Islands (Antarctica)
Authors: Kobashigawa Jesica M. , Robles Carolina A. , Gaiser Rocío F. , Schinca Daniel C. , Scaffardi Lucía B. , Carmarán Cecilia C.
Published: September 2021

Nanoparticles are widely studied due to their possible uses in biological and technological systems. Four psychrotolerant strains of Tulasnella albida isolated from Antarctica were tested and compared in their ability to synthesize silver nanoparticles. The four strains were capable of synthesizing silver nanoparticles with the addition of AgNO3 (final concentration of 0.5 mM), showing similar results under the same conditions: 28°C, 200 rpm, pH 9. Additionally, we registered the synthesis of nanoparticles at 6°C using biomass generated at the same temperature. For the characterization of synthesized nanoparticles, TEM and SEM microscopy analyses were performed. The images obtained showed the existence of spherically shaped silver nanoparticles with a log-normal size distribution centered at 2 nm diameter for 28°C. The largest ones showed a capping shell around them, appearing associated with the formation of small silver nanoparticles. Theoretical calculations of optical absorption based on core-shell Ag-Ag2O nanoparticles were used to characterize the experimental absorption spectra of silver nanoparticles colloids. This work contributes to expanding the studies and possible technological applications of psychrotolerant organisms in the industry, particularly in the green synthesis of nanoparticles at suboptimal conditions.
Mechanism of innate immune reprogramming by a fungal meningitis pathogen
Authors: Dang Eric V. , Lei Susan , Radkov Atanas , Madhani Hiten D.
Published: September 2021

How deadly fungal pathogens overcome mammalian innate immunity is largely unknown. Cryptococcus neoformans, the most common cause of fungal meningitis, induces a pathogenic type 2 response characterized by pulmonary eosinophilia and alternatively activated macrophages. Using forward genetics, we identified a fungal secreted protein, Cpl1, necessary and sufficient to enhance alternative activation of primary macrophages in vitro. Cpl1-enhanced polarization requires Toll-like receptor 4, a known mediator of allergen-induced type 2 responses. Cpl1 is essential for virulence, drives polarization of interstitial macrophages in vivo, and requires type 2 cytokine signaling for its impact on infectivity. C. neoformans selectively associates with polarized interstitial macrophages during infection, supporting a direct hostpathogen interaction. This work identifies a secreted effector produced by a human fungal pathogen that reprograms innate immunity to enable tissue infection.

One sentence summary

Identification of a secreted fungal effector that promotes virulence by enhancing type 2 inflammation
Uip4p modulates nuclear pore complex function in Saccharomyces cerevisiae
Authors: Deolal Pallavi , Jamir Imlitoshi , Mishra Krishnaveni
Published: September 2021

A double membrane bilayer perforated by nuclear pore complexes (NPCs) governs the shape of the nucleus, the prominent distinguishing organelle of a eukaryotic cell. Despite the absence of lamins in yeasts, the nuclear morphology is stably maintained and shape changes occur in a regulated fashion. In a quest to identify factors that contribute to regulation of nuclear shape and function in Saccharomyces cerevisiae, we used a fluorescence imaging based approach. Here we report the identification of a novel protein, Uip4p, that is required for regulation of nuclear morphology. Loss of Uip4 compromises NPC function and loss of nuclear envelope (NE) integrity. Our localisation studies show that Uip4 localizes to the NE and endoplasmic reticulum (ER) network. Furthermore, we demonstrate that the localization and expression of Uip4 is regulated during growth, which is crucial for NPC distribution.
Category-specific representational patterns in left inferior frontal and temporal cortex reflect similarities and differences in the sensorimotor and distributional properties of concepts
Authors: Carota Francesca , Kriegeskorte Nikolaus , Nili Hamed , Pulvermüller Friedemann
Published: September 2021

Neuronal populations code similar concepts by similar activity patterns across the human brain’s networks supporting language comprehension. However, it is unclear to what extent such meaning-to-symbol mapping reflects statistical distributions of symbol meanings in language use, as quantified by word co-occurrence frequencies, or, rather, experiential information thought to be necessary for grounding symbols in sensorimotor knowledge. Here we asked whether integrating distributional semantics with human judgments of grounded sensorimotor semantics better approximates the representational similarity of conceptual categories in the brain, as compared with each of these methods used separately. We examined the similarity structure of activation patterns elicited by action- and object-related concepts using multivariate representational similarity analysis (RSA) of fMRI data. The results suggested that a semantic vector integrating both sensorimotor and distributional information yields best category discrimination on the cognitive-linguistic level, and explains the corresponding activation patterns in left posterior inferior temporal cortex. In turn, semantic vectors based on detailed visual and motor information uncovered category-specific similarity patterns in fusiform and angular gyrus for object-related concepts, and in motor cortex, left inferior frontal cortex (BA 44), and supramarginal gyrus for action-related concepts.
Characterization of SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 on cell entry, host range, and sensitivity to convalescent plasma and ACE2 decoy receptor
Authors: Ren Wenlin , Ju Xiaohui , Gong Mingli , Lan Jun , Yu Yanying , Long Quanxin , Zhang Yu , Zhong Jin , Zhong Guocai , Wang Xinquan , Huang Ailong , Zhang Rong , Ding Qiang
Published: September 2021

Recently, highly transmissible SARS-CoV-2 variants B.1.617.1 (Kappa), B.1.617.2 (Delta) and B.1.618 were identified in India with mutations within the spike proteins. The spike protein of Kappa contains four mutations E154K, L452R, E484Q and P681R, and Delta contains L452R, T478K and P681R, while B.1.618 spike harbors mutations Δ145-146 and E484K. However, it remains unknown whether these variants have altered in their entry efficiency, host tropism, and sensitivity to neutralizing antibodies as well as entry inhibitors. In this study, we found that Kappa, Delta or B.1.618 spike uses human ACE2 with no or slightly increased efficiency, while gains a significantly increased binding affinity with mouse, marmoset and koala ACE2 orthologs, which exhibits limited binding with WT spike. Furthermore, the P618R mutation leads to enhanced spike cleavage, which could facilitate viral entry. In addition, Kappa, Delta and B.1.618 exhibits a reduced sensitivity to neutralization by convalescent sera owning to the mutation of E484Q, T478K, Δ145-146 or E484K, but remains sensitive to entry inhibitors-ACE2-lg decoy receptor. Collectively, our study revealed that enhanced human and mouse ACE2 receptor engagement, increased spike cleavage and reduced sensitivity to neutralization antibodies of Kappa, Delta and B.1.618 may contribute to the rapid spread of these variants and expanded host range. Furthermore, our result also highlighted that ACE2-lg could be developed as broad-spectrum antiviral strategy against SARS-CoV-2 variants.
Discovery of highly potent pancoronavirus fusion inhibitors that also effectively inhibit COVID-19 variants from the UK (Alpha), South Africa (Beta), and India (Delta)
Authors: Curreli Francesca , Ahmed Shahad , Victor Sofia M. B. , Drelich Aleksandra , Panda Siva S. , Altieri Andrea , Kurkin Alexander V. , Tseng Chien-Te K. , Hillyer Christopher D. , Debnath Asim K.
Published: September 2021

We report here the discovery of several highly potent small molecules that showed low nM potency against SARS-CoV (IC50: as low as 13 nM), SARS-CoV-2 (IC50: as low as 23 nM), and MERS-CoV (IC50: as low as 76 nM) in pseudovirus based assays with excellent selectivity indices (SI: as high as > 5000) demonstrating their pancoronavirus inhibition. Some compounds also show 100% inhibition of CPE (IC100) at 1.25 µM against an authentic SARS-CoV-2 (US_WA-1/2020). Furthermore, the most active inhibitors also potently inhibited variants of concerns (VOCs), such as the UK (B.1.1.7), South Africa (B.1.351), and Delta variant (B.1.617.2), originated in India. We confirmed that one of the potent inhibitors binds to the prefusion spike protein trimer of SARS-CoV-2 by SPR. Besides, we showed that they inhibit virus-mediated cell-cell fusion. The ADME data of one of the most active inhibitors, NBCoV1, show drug-like properties. In vivo PK of NBCoV1 in rats demonstrated excellent half-life (t1/2) of 11.3 h, mean resident time (MRT) of 14.2 h, and oral bioavailability. We expect the lead inhibitors to pave the way for further development to preclinical and clinical candidates.
Efficient computation of Faith's phylogenetic diversity with applications in characterizing microbiomes
Authors: Armstrong George , Cantrell Kalen , Huang Shi , McDonald Daniel , Haiminen Niina , Carrieri Anna Paola , Zhu Qiyun , Gonzalez Antonio , McGrath Imran , Beck Kristen L. , Hakim Daniel , Havulinna Aki S. , Méric Guillaume , Niiranen Teemu , Lahti Leo , Salomaa Veikko , Jain Mohit , Inouye Michael , Swafford Austin D. , Kim Ho-Cheol , Parida Laxmi , Vázquez-Baeza Yoshiki , Knight Rob
Published: September 2021

The number of publicly available microbiome samples is continually growing. As data set size increases, bottlenecks arise in standard analytical pipelines. Faith's phylogenetic diversity (Faith's PD) is a highly utilized phylogenetic alpha diversity metric that has thus far failed to effectively scale to trees with millions of vertices. Stacked Faith's phylogenetic diversity (SFPhD) enables calculation of this widely adopted diversity metric at a much larger scale by implementing a computationally efficient algorithm. The algorithm reduces the amount of computational resources required, resulting in more accessible software with a reduced carbon footprint, as compared to previous approaches. The new algorithm produces identical results to the previous method. We further demonstrate that the phylogenetic aspect of Faith's PD provides increased power in detecting diversity differences between younger and older populations in the FINRISK study's metagenomic data.
Professionalism in built environment research: beyond integrity and good practice
Authors: Ofori George
Published: September 2021

Purpose

Professionalism indicates a devotion to and demonstration of exceptional performance and achievement in any activity. The built environment comprises the physical items required for economic activity, long-term national development and social well-being. Studies show a need to improve many aspects of the built environment and the sector which creates it. Researchers should contribute to this improvement effort. It is suggested that researchers should demonstrate professionalism, but there is no agreement on how professionalism in research is determined. It is necessary to consider what constitutes professionalism in built environment research and how it can be developed.

Design/methodology/approach

An exploratory study is presented. It considers major works on the nature of the built environment and its sector, and factors influencing research on them; and draws on works on research ethics, integrity and good practice to propose a framework for professionalism in built environment research.

Findings

More work is needed to improve the built environment and its sector. Professionalism in built environment research will make the contribution of such research to this effort effective. This professionalism should be conceptualised, developed and continuously enhanced.

Research limitations/implications

This first attempt to formulate a framework for professionalism in built environment research is based on a review of the major relevant literature. Subsequent works can test this framework empirically.

Social implications

The professional built environment researcher will be committed to contributing to society.

Originality/value

This is the first work on professionalism in research on the built environment. The framework provides the basis for further studies on the subject.
Last-mile challenges in on-demand food delivery during COVID-19: understanding the riders' perspective using a grounded theory approach
Authors: Puram Praveen , Gurumurthy Anand , Narmetta Mukesh , Mor Rahul S.
Published: September 2021

Purpose

This paper aims to explore the last-mile (LM) challenges faced by on-demand food delivery (ODFD) riders during the coronavirus pandemic. This study contributes to the literature on the less-explored domain of ODFD services.

Design/methodology/approach

A grounded theory methodology is used. Riders working for multiple ODFD firms in various urban and semi-urban areas of India were interviewed. Open, axial and selective coding of interview transcripts was done.

Findings

A grounded model is developed consisting of riders' challenges represented broadly under four core categories: Operational, Customer-related, Organisational and Technological issues. The study indicates that while some of the challenges are inherent to the ODFD supply chain, these have been visibly exposed and intensified by COVID-19, while other challenges are specific to the pandemic.

Research limitations/implications

The model is a qualitative proposition representing LM delivery issues in ODFD services faced by the riders in India's urban and semi-urban areas during the COVID-19 pandemic. Other countries may face similar problems, but further studies are necessary to confirm or refute the findings.

Practical implications

ODFD companies must address the riders' issues to better adapt to the current and future disruptions and improve riders' quality of work–life to achieve operational excellence.

Originality/value

This study builds on the extant ODFD literature by focusing on one of its less addressed aspects: the working conditions of the riders. This work is conducted amid the COVID-19 pandemic in the context of a developing country and aims to study the challenges in ODFD operations.
Moderating effect of gender on adoption of digital health consultation: a patient perspective study
Authors: Dash Ajitabh , Sahoo Anjan Kumar
Published: September 2021

Purpose

The purpose of this paper is to understand the factors influencing the adoption decision of patients towards digital consultation in India with gender as a moderating variable. This study is based on the unified theory of acceptance and use of technology (UTAUT2) framework for examining the factors influencing adoption decisions for digital consultation and to what extent this leads to continuous usage intention.

Design/methodology/approach

Based on the UTAUT2 framework, this study proposed a set of hypotheses that were tested using structural equation modeling. This study was based on primary data collected from 462 sample respondents using the judgemental sampling method who had experience of using digital health consultation in India.

Findings

Findings of this study revealed significant and positive causation in the behavioural intention (BI) of a patient to adopt digital health consultation arising out of performance expectancy, effort expectancy, social influence, facilitating condition and price value; however, habit is insignificantly associated with the same. Furthermore, the results of this study also revealed that the BI of a patient towards digital health consultation is significantly moderated by their gender.

Originality/value

This study conceptually strengthens the present body of literature on the adoption behaviour by contributing certain new dimensions in the context of digital health consultations and will also help policymakers and service providers in crafting their strategy for promoting the adoption of digital health consultation.
Malaysian SMEs m-commerce adoption: TAM 3, UTAUT 2 and TOE approach
Authors: Salimon Maruf Gbadebo , Kareem Olanrewaju , Mokhtar Sany Sanuri Mohd , Aliyu Olayemi Abdullateef , Bamgbade Jibril Adewale , Adeleke Adekunle Qudus
Published: September 2021

Purpose

The purpose of this study is to examine the factors that influence Malaysian Small and Medium Enterprises (SMEs) to adopt mobile commerce (m-commerce) by integrating the constructs of Technology Acceptance Model 3 (TAM 3), Universal Theory of Acceptance and Use of Technology 2 and Technology-Organization-Environment model. Though numerous m-commerce adoption (MCA) studies have been conducted, lesser attention is paid to how hedonic motivation (HM) can influence organizational users such as SMEs. This study bridges the gap by integrating the three models to provide a new lens to guide SMEs.

Design/methodology/approach

To examine the factors that influence the adoption of m-commerce, the researchers collected data from SMEs in Malaysia using an online survey. The sample size of the participants was determined through the available list provided by SME Corp Malaysia. The researchers also used Krejcie and Morgan’s sample size and G * Power techniques to determine that the sample size was appropriate. The data collected were analyzed using partial least square-structural equation modeling.

Findings

The findings of this study reveal that technological factors (computer self-efficacy [CSE], result demonstrability [RD] and computer anxiety [CA]) positively and significantly influenceMCA. Likewise, the organizational/environmental factors (m-commerce knowledge, pressure from trading partners and pressure from competitors) positively and significantly influenceMCA. The moderating influence of HM was also achieved on the relationship betweenCSEandRD. However, the proposed hedonic moderating relationship betweenCAand the adoption of m-commerce is not significant.

Research limitations/implications

This study integrates three models to explain the adoption of m-commerce among SMEs in Malaysia and tested the moderating influence of HM. The results obtained better explain the decision by the SMEs to use m-commerce.

Originality/value

The study critically considered how m-commerce can be adopted by SMEs in Malaysia, which previous studies have largely ignored. Considering this, the study, therefore, advances a new relationship by integrating Technology-organization-environment model with TAM 3 and the moderating influence of HM to explainMCAamong SMEs. This paper is one of the few research studies to test the moderating influence of HM in this regard.
Restoring marine ecosystems: Spatial reef configuration triggers taxon‐specific responses among early colonizers
Authors: Wilms Tim J. G. , Norðfoss Pauli H. , Baktoft Henrik , Støttrup Josianne G. , Kruse Bo M. , Svendsen Jon C.
Published: September 2021

The longstanding debate in conservation biology on the importance of single large or several small (SLOSS) habitats for preserving biodiversity remains highly relevant, given the ongoing degradation and loss of natural habitats world‐wide. Restoration efforts are often constrained by limited resources, and insights from SLOSS studies therefore have important implications if restoration efforts can be optimized by manipulating the spatial configuration of restored habitats. Yet, the relevance of SLOSS for habitat restoration remains largely unexplored.

Here, we report the effects of spatial reef configuration on early colonization of marine organisms after restoring boulder reef habitats. Reefs were restored in single large (SL) and several small (SS) designs in the western Baltic Sea, where century‐long boulder extraction has severely degraded large reef areas and likely exacerbated regional declines in commercially important gadoids (Gadidae spp.). We sampled the field sites using remote underwater video systems in a before‐after control‐impact (BACI) design and obtained probabilistic inferences on restoration and SLOSS effects from Bayesian hierarchical models.

Probabilities of a positive restoration effect were high (>95%) for gadoids, labrids and demersal gobies, moderate (60%–75%) for species richness and sand gobies, and low (<5%) for flatfish abundance. Notably, gadoid abundance increased 60‐fold and 129‐fold on average at SL and SS respectively. The species composition at restored reefs deviated from control sites, mainly driven by large‐bodied piscivores.

Spatial reef configuration had the strongest effect on small‐bodied mesopredators, including gobies, which were more abundant at SS and driving distinct species assemblages between the reef designs. In addition to providing suitable conditions for reef species, results suggest that SS can also benefit soft‐bottom taxa, possibly through a dispersed predator‐mediated effect relative to SL.

Synthesis and applications. This study demonstrates that boulder reef restoration can strongly promote the abundance of exploited gadoids (e.g. Atlantic cod) and is therefore a promising management tool to support top‐down controls by predatory fishes in degraded marine systems. The higher abundance of mesopredators at reefs with a ‘several small’ configuration suggests that the SLOSS dilemma could have long‐term implications for trophic structure and resilience of restored habitats, and should therefore become an important facet within restoration strategies.