bluuebunny/crossref_metadata_2025 huggingface dataset:
Haplotype-resolvedde novogenome assemblies of four coniferous tree species
Authors: Shirasawa Kenta , Mishima Kentaro , Hirakawa Hideki , Hirao Tomonori , Tsubomura Miyoko , Nagano Soichiro , Iki Taiichi , Isobe Sachiko , Takahashi Makoto
Published: November 2022

Coniferous trees in gymnosperm are an important source of wood production. Because of their long lifecycle, the breeding programs of coniferous tree are time- and labor-consuming. Genomics could accelerate the selection of superior trees or clones in the breeding programs; however, the genomes of coniferous trees are generally giant in size and exhibit high heterozygosity. Therefore, the generation of long contiguous genome assemblies of coniferous species has been difficult. In this study, we optimized the DNA library preparation protocols and employed high-fidelity (HiFi) long-read sequencing technology to sequence and assemble the genomes of four coniferous tree species,Larix kaempferi, Chamaecyparis obtusa, Cryptomeria japonica, andCunninghamia lanceolata. Genome assemblies of the four species totaled 13.5 Gb (L. kaempferi), 8.5 Gb (C. obtusa), 9.2 Gb (C. japonica), and 11.7 Gb (C. lanceolata), which covered 99.6% of the estimated genome sizes on average. The contig N50 value, which indicates assembly contiguity, ranged from 1.2 Mb inC. obtusato 16.0 Mb inL. kaempferi, and the assembled sequences contained, on average, 89.2% of the single-copy orthologs conserved in embryophytes. Assembled sequences representing alternative haplotypes covered 70.3–95.1% of the genomes, suggesting that the four coniferous tree genomes exhibit high heterozygosity levels. The genome sequence information obtained in this study represents a milestone in tree genetics and genomics, and will facilitate gene discovery, allele mining, phylogenetics, and evolutionary studies in coniferous trees, and accelerate forest tree breeding programs.
Gut Microbiome Prediction: From Current Human Evidence to Future Possibilities
Authors: Pramanick Rinku , Gazara Rajesh Kumar , Ahmad Rafi
Published: November 2022

The gut microbiome is an indispensable component of the human body. Alteration in the gut microbiota composition leads to various diseases such as obesity, Type 2 Diabetes, Inflammatory Bowel Syndrome, and depression. Microbiome-based precision tests offer a futuristic strategy for wellness and longevity. However, this approach is limited by the lack of definition of a healthy microbiome in different populations and accurate disease prediction.

In this study, we aimed to capture the healthy gut microbiome for different populations using the xNARA Gut Profile Test kit and in-house built proprietary algorithm and reference databases. We found that gut microbiome of different populations from India, UAE, and Singapore varied significantly, indicating a distinct geographic gut microbiome signature and Gut Health Index. The gut microbial diversity as measured by the Shannon index revealed UAE had significantly greater alpha diversity than India and Singapore.Prevotella copri(19.27%),Faecalibacterium prausnitzii(4.08%) andLevilactobacillus brevis(4.0%) were the predominant species in the Indian gut.Faecalibacterium prausnitzii(8.54%),Blautia obeum(8.10%), andPhocaeicola vulgatus(4.6%) were primarily present in Singapore participants whereasPrevotella copri(14.92%),Blautia obeum(6.09%) andRoseburia intestinalis(5.81%) were present in UAE participants. Beta diversity indicated the gut microbiota of Indian-origin participants in Singapore and UAE clustered with the indigenous inhabitants of Singapore and UAE. This highlights that geographic location has a profound effect on shaping the gut microbiome architecture than ethnicity. Regional diet and lifestyle could be crucial factors responsible for shaping the gut microbiome. The prediction accuracy of the xNARA Gut algorithm ranged from 66.66-100% when matched with the blood reports. Participants agreed with the xNARA disease risk outcomes for metabolic conditions (60%-100%), gastrofitness (62.5%-100%), mental health (50%-100%), skin conditions (50%-100%) and physical fitness (50%-100%). These observations imply the promising role of gut-based personalized diet and probiotic recommendations for lifestyle and wellness management.
STopover captures spatial colocalization and interaction in the tumor microenvironment using topological analysis in spatial transcriptomics data
Authors: Bae Sungwoo , Lee Hyekyoung , Na Kwon Joong , Lee Dong Soo , Choi Hongyoon , Kim Young Tae
Published: November 2022

Unraveling the spatial configuration of the tumor microenvironment (TME) is key to understanding tumor-immune interactions to translate them into immuno-oncology. With the advent of spatially resolved transcriptomics (SRT), the TME could be dissected for whole cell types across numerous RNAs. We suggest a novel approach, STopover, which performs topological analysis to compute the colocalization patterns between cell types and map the location of cell□cell interactions. While gradually lowering the threshold for the feature, the connected components (CCs) were extracted based on the spatial distance between the unit tissue region and the persistence of the CCs. Local and global Jaccard indices were calculated between the CCs of a feature pair to measure the extent of spatial overlap. The STopover was applied to various lung cancer data obtained from SRT platforms, both barcode and image-based SRT, and could explain the infiltration patterns of immune and stromal cells in the TME. Moreover, the method predicted the top cell□cell communication based on the ligand□receptor database and highlighted the main region of the interaction. STopover is a tool to decipher spatial interaction in the tissue and shed light on the pathophysiology underlying the microenvironment.
Contemporary human H3N2 influenza A viruses require a low threshold of suitable glycan receptors for efficient infection
Authors: Spruit Cindy M. , Sweet Igor R. , Bestebroer Theo , Lexmond Pascal , Qiu Boning , Damen Mirjam J.A. , Fouchier Ron A. M. , Snijder Joost , Herfst Sander , Boons Geert-Jan , de Vries Robert P.
Published: November 2022

Recent human H3N2 influenza A viruses (IAV) have evolved to employ elongated glycans terminating in α2,6-linked sialic acid as their receptors. These glycans are displayed in low abundancies by cells commonly employed to propagate these viruses (MDCK and hCK), resulting in low or no viral propagation. Here, we examined whether the overexpression of the glycosyltransferases B3GNT2 and B4GALT1, which are responsible for the elongation of poly-N-acetyllactosamines (LacNAc), would result in improved A/H3N2 propagation. Stable overexpression of B3GNT2 and B4GALT1 in MDCK and hCK cells was achieved by lentiviral integration and subsequent antibiotic selection and confirmed by qPCR and protein mass spectrometry experiments. Flow cytometry and glycan mass spectrometry experiments using the B3GNT2 and/or B4GALT1 knock-in cells demonstrated increased binding of viral hemagglutinins and the presence of a larger number of LacNAc repeating units, especially on hCK-B3GNT2 cells. An increase in the number of glycan receptors did, however, not result in a greater infection efficiency of recent human H3N2 viruses. Based on these results, we propose that H3N2 IAVs require a low number of suitable glycan receptors to infect cells and that an increase in the glycan receptor display above this threshold does not result in improved infection efficiency.
Estimates for the astrocyte endfoot sheath permeability of the extra-cellular pathway
Authors: Koch Timo , Vinje Vegard , Mardal Kent-André
Published: November 2022

Background

Astrocyte endfoot processes are believed to cover all micro-vessels in the brain cortex and may play a significant role in fluid and substance transport into and out of the brain parenchyma. Detailed fluid mechanical models of diffusive and advective transport in the brain are promising tools to investigate theories of transport.

Methods

We derive theoretical estimates of astrocyte endfoot sheath permeability for advective and diffusive transport and its variation in microvascular networks from mouse brain cortex. The networks are based on recently published experimental data and generated endfoot patterns are based on Voronoi tessellations of the perivascular surface. We estimate corrections for projection errors in previously published data.

Results

We provide structural-functional relationships between vessel radius and resistance that can be directly used in flow and transport simulations. We estimate endfoot sheath filtration coefficients in the rangeLp= 0.2 × 10−10m Pa−1s−1to 2.7 × 10−10m Pa−1s−1, diffusion membrane coefficients in the rangeCM= 0.5 × 103m−1to 6 × 103m−1, and gap area fractions in the range 0.2 % to 0.6 %.

Conclusions

The astrocyte endfoot sheath surrounding microvessels forms a secondary barrier to extra-cellular transport, separating the extra-cellular space of the parenchyma and the perivascular space outside the endothelial layer. The filtration and membrane diffusion coefficients of the endfoot sheath are estimated to be an order of magnitude lower than the extra-cellular matrix while being two orders of magnitude higher than the vessel wall.
Dynamic traction force measurements of migrating immune cells in 3D matrices
Authors: Böhringer David , Cóndor Mar , Bischof Lars , Czerwinski Tina , Gampl Niklas , Ngo Phuong Anh , Bauer Andreas , Voskens Caroline , López-Posadas Rocío , Franze Kristian , Budday Silvia , Mark Christoph , Fabry Ben , Gerum Richard
Published: November 2022

Immune cells such as natural killer (NK) cells migrate with high speeds of several µm/min through dense tissue, but the traction forces are unknown. We present a method to measure dynamic traction forces of fast migrating cells in non-linear biopolymer matrices. The method accounts for the mechanical non-linearity of the 3D tissue matrix and can be applied to time series of confocal or bright-field image stacks. The method is highly sensitive over a large range of forces and object sizes, from ∼1 nN for axon growth cones up to ∼10 µN for mouse intestinal organoids. We find that NK cells display bursts of large traction forces that increase with matrix stiffness and facilitate migration through tight constrictions.
Modelling dementia inDrosophilauncovers shared and specific targets of TDP-43 proteinopathy across ALS and FTD relevant circuits
Authors: Godfrey R Keating , Bjork Reed T , Alsop Eric , Chauhan Brijesh S , Ruvalcaba Hillary C , Antone Jerry , Michael Allison F , Williams Christi , Hala’ufia Grace , Blythe Alexander D , Hall Megan , Keuren-Jensen Kendall Van , Zarnescu Daniela C
Published: November 2022

Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) comprise a spectrum of neurodegenerative diseases linked to TDP-43 proteinopathy, which at the cellular level, is characterized by loss of nuclear TDP-43 and accumulation of cytoplasmic TDP-43 puncta that ultimately cause RNA processing defects including dysregulation of splicing, mRNA transport and translation. Complementing our previous models of ALS, here we report a novel model of FTD based on overexpression of TDP-43 in theDrosophilamushroom body (MB) circuit. This model recapitulates several aspects of FTD pathology including age-dependent neuronal loss, and nuclear depletion and cytoplasmic accumulation of TDP-43, accompanied by behavioral deficits in working memory and sleep that occur before axonal degeneration ensues. RNA immunoprecipitations identify several candidate mRNA targets of TDP-43 in MBs, some of which are unique to the MB circuit while others are shared with motor neurons. Among the latter is the glypican Dally-like-protein (Dlp), a modulator of Wg/Wnt signaling. Using genetic interactions we show that overexpression of Dlp in MBs mitigates TDP-43 dependent working memory deficits. These results highlight the utility of modelling TDP-43 proteinopathy inDrosophilaand provide a novel platform for studying the molecular mechanisms underlying FTD, and potentially uncovering shared and circuit specific vulnerabilities in ALS/FTD.
Independent control over cell patterning and adhesion on hydrogel substrates for tissue interface mechanobiology
Authors: Prahl Louis S. , Porter Catherine M. , Liu Jiageng , Viola John M. , Hughes Alex J.
Published: November 2022

Replicating organizational principles that establish fine-scale tissue structure is critical to our capacity for building functional replacement tissues. Tissue boundaries such as epithelial-mesenchymal interfaces are engines for morphogenesisin vivo. However, despite a wealth of micropatterning approaches available to control tissue size, shape, and mechanical environmentin vitro, fine-scale spatial control of cell composition within tissue constructs remains an engineering challenge. To address this, we augment DNA “velcro” technology for selective patterning of ssDNA-labeled cells with long-term culture on mechanically defined polyacrylamide hydrogels. We co-functionalize photoactive benzophenone-containing polyacrylamide gels (BP-PA gels) with spatially precise ssDNA features that confer temporary cell adhesion and with extracellular matrix (ECM) proteins that confer long-term adhesion. We find that co-functionalization does not compromise ssDNA patterning fidelity or cell capture, nor hydrogel mechanical properties or mechanosensitive fibroblast spreading, enabling mechanobiology studies of precise cell interfaces. We then co-pattern colonies of fibroblasts and epithelial cells to study interface formation and extracellular signal-related kinase (ERK) activity at cellular contacts. Combining DNA velcro and ECM functionalization approaches provides independent control of initial cell placement, adhesion, and mechanical environment, constituting a new tool for studying biological interfaces and for programming multicellular interactions in engineered tissues.
Proteasomal activity is differentially regulated in source and sink tissues of Arabidopsis
Authors: Wang Haojie , Dongen Joost T. van , schippers Jos HM
Published: November 2022

Protein homeostasis controlled by the 26S proteasome plays a pivotal role in the adaption of plants to environmental stress, contributing to survival and longevity. During ageing in animals, proteasome activity declines resulting in senescence, however, in plants this is so far largely unexplored. Herein, we found that 26S proteasome capacity deteriorates with leaf age, while 20S proteasome activity increases. Interestingly, expression of proteasomal genes increases during leaf senescence, both at the steady-state mRNA level and poly-ribosome associated mRNA level. However, the increase in transcript level does not correlate with protein abundance and proteasome activity in senescing leaves. Furthermore, chemical inhibition of the proteasome results in accelerated leaf senescence. Interestingly, deterioration of proteasome activity in senescent leaves could be restored by cytokinin application. In Arabidopsis, feed-back regulation between proteasome activity and gene expression exists, and we propose that this is the cause for the high amount of proteasomal subunit mRNA during leaf senescence. In sink tissues like mature siliques and seeds, an increased 26S proteasome activity is observed. This increased activity is mainly due to enhanced proteasome assembly. This work provides new insights into the regulation of proteasome activity which deepens our understanding on source-sink relations and their impact on plant yield.
Cell response to extracellular matrix energy dissipation outweighs rigidity sensing
Authors: Huerta-López Carla , Clemente-Manteca Alejandro , Velázquez-Carreras Diana , Espinosa Francisco M. , Sanchez Juan G. , Sáez Pablo , Martínez-del-Pozo Álvaro , García-García María , Martín-Colomo Sara , Rodríguez-Blanco Andrea , Esteban-González Ricardo , Martín-Zamora Francisco M. , Gutierrez-Rus Luis I. , García Ricardo , Roca-Cusachs Pere , Elosegui-Artola Alberto , del Pozo Miguel A. , Herrero-Galán Elías , Plaza Gustavo R. , Alegre-Cebollada Jorge
Published: November 2022

The mechanical properties of the extracellular matrix (ECM) determine cell differentiation, proliferation and migration through mechanoresponsive proteins including YAP. However, how different mechanical signals cooperate, synergize or compete to steer cell behavior remains poorly understood. Here, we have examined competition between the two major ECM mechanical cues, i.e. rigidity, which activates cell mechanosensing, and viscous energy dissipation, which reduces stiffness blunting cell mechanotransduction. To trigger competition, we have engineered protein hydrogels allowing concomitant modulation of stiffness and viscosity by mechanisms characteristic of native ECM. Culturing cells on these hydrogels, we have found that substrate energy dissipation attenuates YAP mechanosensing prevailing over stiffness cues. Hampered YAP activation on more dissipative substrates correlates with faster actin flow and smaller focal adhesions. Mechanistically, inhibition of actomyosin contractility reverses the outcome of the competition between rigidity and energy dissipation. Our results highlight the dominating contribution of substrate viscosity to the biology of the cell.
The Centralspindlin proteins Pavarotti and Tumbleweed work with WASH to regulate Nuclear Envelope budding
Authors: Davidson Kerri A. , Nakamura Mitsutoshi , Verboon Jeffrey M. , Parkhurst Susan M.
Published: November 2022

Nuclear envelope (NE) budding is a nuclear pore independent nuclear export pathway, analogous to the egress of herpesviruses, and required for protein quality control, synapse development and mitochondrial integrity. The physical formation of NE buds is dependent on the Wiskott-Aldrich Syndrome protein Wash, its regulatory complex (SHRC), and Arp2/3, and requires Wash’s actin nucleation activity. However, the machinery governing cargo recruitment and organization within the NE bud remains unknown. Here, we identify Pavarotti (Pav) and Tumbleweed (Tum) as new molecular components of NE budding. Pav and Tum interact directly with Wash and define a second nuclear Wash-containing complex required for NE budding. Interestingly, we find that the actin bundling activities of Wash and Pav are required, suggesting a structural role in the physical and/or organizational aspects of NE buds. Thus, Pav and Tum are providing exciting new entry points into the physical machineries of this alternative nuclear export pathway for large cargos during cell differentiation and development.
Three-dimensional molecular architecture of mouse organogenesis
Authors: Qu Fangfang , Li Wenjia , Xu Jian , Zhang Ruifang , Ke Jincan , Ren Xiaodie , Meng Xiaogao , Qin Lexin , Zhang Jingna , Lu Fangru , Zhou Xin , Luo Xi , Zhang Zhen , Wu Guangming , Pei Duanqing , Chen Jiekai , Cui Guizhong , Suo Shengbao , Peng Guangdun
Published: November 2022

Mammalian embryos have sophisticated cell organizations that are orchestrated by molecular regulation at cellular and tissue level. It has recently been appreciated that the cells that make up the animal body themselves harbor significant heterogeneity in the context of both cellular and particularly spatial dimension. However, current spatial transcriptomics profiling of embryonic tissues either lack three-dimensional representation or are restricted to limited depth and organs. Here, we reported a holistic spatial transcriptome atlas of all major organs at embryonic day 13.5 of mouse embryo and delineated a 3D rendering of the molecular regulation of embryonic patterning. By integrating with corresponding single-cell transcriptome data, the spatial organogenesis atlas provides rich molecular annotation of the dynamic organ nature, spatial cellular interaction, embryonic axes and divergence of cell fates underlying mammalian development, which would pave the way for precise organ-engineering and stem-cell based regenerative medicine.
Binary or non-binary fission? Reproductive mode of a predatory bacterium depends on prey size
Authors: Pląskowska Karolina , Makowski Łukasz , Strzałka Agnieszka , Zakrzewska-Czerwińska Jolanta
Published: November 2022

Most eukaryotic and bacterial cells divide by binary fission, where one mother cell produces two progeny cells, or, rarely, by non-binary fission. All bacteria studied to date use only one of these two reproduction modes. Here, we demonstrate for the first time that the predatory bacteriumBdellovibrio bacteriovorusreproduces through both binary and non-binary fission. Switching between the two modes correlates with the prey size. In relatively small host cells,B. bacteriovorusundergoes binary fission; the FtsZ ring assembles in the midcell and the mother cell splits into two daughter cells. In larger host cells,B. bacteriovorusswitches to non-binary fission and creates multiple FtsZ rings to produce three or more daughter cells. Completion of bacterial cell cycle critically depends on precise spatiotemporal coordination of chromosome replication and segregation with other cell-cycle events, including cell division. Our studies reveal thatB. bacteriovorusalways initiates chromosome replication at the invasive pole of the cell, but the spatiotemporal choreography of subsequent steps depends on the fission mode and/or the number of progeny cells. In non-binary dividing filaments producing five or more progeny cells, the last round(s) of replication may also be initiated at the noninvasive pole. Finally, we show that binary-dividingB. bacteriovorusneeds to extensively rebuild the flagellated pole of the mother cell to turn it into the invasive pole of a daughter cell. Altogether, we find thatB. bacteriovorusreproduces through bimodal fission and that extracellular factors, such as the host size, can shape replication choreography, providing new insights about bacterial life cycles.
BtuB TonB-dependent transporters and BtuG surface lipoproteins form stable complexes for vitamin B12uptake in gutBacteroides
Authors: Abellon-Ruiz Javier , Jana Kalyanashis , Silale Augustinas , Frey Andrew M. , Baslé Arnaud , Trost Matthias , Kleinekathöfer Ulrich , van den Berg Bert
Published: November 2022

Vitamin B12(cobalamin) is the most complex vitamin and essential for many human gut microbes. However, cobalamin is synthesised only by a limited number of bacteria, making many gut microbes dependent on scavenging to meet their cobalamin requirements. Since bacterial densities in the gut are extremely high, competition for cobalamin is severe, making it a keystone micronutrient that shapes human gut microbial communities. Contrasting with Enterobacteria likeEscherichia coliwhich only have one outer membrane (OM) transporter dedicated to B12uptake (BtuB), members of the dominant genusBacteroidesoften encode several vitamin B12OM transporters together with a conserved array of surface-exposed B12-binding lipoproteins. Here we show, via X-ray crystallography, cryogenic electron microscopy (cryoEM) and molecular dynamics (MD) simulations, that the BtuB1 and BtuB2 transporters from the prominent human gut bacteriumBacteroides thetaiotaomicronform stable complexes with the surface-exposed lipoproteins BtuG1 and BtuG2. The lipoproteins cap the external surface of their cognate BtuB transporter and, when open, capture B12via electrostatic attraction. After B12capture, the BtuG lid closes, with concomitant transfer of the vitamin to the BtuB transporter and subsequent transport. We propose that TonB-dependent, lipoprotein-assisted small molecule uptake is a general feature ofBacteroides spp. that is important for the success of this genus in colonising the human gut.
Obligate Endosymbiosis Explains Genome Expansion During Eukaryogenesis
Authors: von der Dunk Samuel H. A. , Hogeweg Paulien , Snel Berend
Published: November 2022

The endosymbiosis of an alpha-proteobacterium that gave rise to mitochondria was one of the key events in eukaryogenesis. Common patterns in eukaryogenesis and present-day endosymbiotic relations include genomic streamlining of the symbiont, endosymbiotic gene transfer, and regulatory control by the host through protein targeting to the symbiont. One unique outcome for eukaryogenesis was a much more complex cell with a large genome, which may or may not be related to the mitochondrial endosymbiosis. Despite the existence of many plausible hypotheses for the observed patterns, a constructive evolutionary model in which these hypotheses can be studied is still lacking.

Here we construct an evolutionary model of cell-cycle regulation to study how obligate endosymbiosis between two prokaryote-like cells impacts cellular behavior and genome evolution. The model does not predefine an explicit fitness criterion and thereby allows for the evolution of various emergent behaviors. For instance, even though we do not allow for communication between host and symbiont, they achieve implicit cell-cycle coordination through their interaction with the environment. This evolved cell-cycle coordination can drive genome expansion as well as symmetry breaking in genome size. Many replicate runs of our evolution experiment yield organisms with a large host and small symbiont genome, but interestingly, some yield the opposite. Still on long timescales, organisms with a large host and small symbiont genome perform best, and mimic the outcome of eukaryogenesis.

By designing and studying a constructive evolutionary model of obligate endosymbiosis, we uncovered some of the forces that may drive the patterns observed in nature. Our results provide a theoretical foundation for patterns related to the mitochondrial endosymbiosis, such as genome size asymmetry, and reveal evolutionary outcomes that have not been considered so far, such as cell-cycle coordination without direct communication.
Purging genomes of contamination eliminates systematic bias from evolutionary analyses of ancestral genomes
Authors: Bálint Balázs , Merényi Zsolt , Hegedüs Botond , Grigoriev Igor V. , Hou Zhihao , Földi Csenge , Nagy László G.
Published: November 2022

Contamination of genomes and sequence databases is an increasingly recognized problem, however, efficient tools for removing alien sequences are still sparse and the impact of impure data on downstream analyses remains to be fully explored. Here, we present a new, highly sensitive tool, ContScout, for removing contamination from genomes, evaluate the level of contamination in 844 published eukaryotic genomes and show that contaminating proteins can severely impact analyses of genome evolution. Via benchmarking against synthetic data, we demonstrate that ContScout achieves high specificity and sensitivity when separating sequences of different high level taxa from each other. Furthermore, by testing on manually curated data we show that ContScout by far outperforms pre-existing tools. In the context of ancestral genome reconstruction, an increasingly common approach in evolutionary genomics, we show that contamination leads to spurious early origins for gene families and inflates gene loss rates several fold, leading to false notions of complex ancestral genomes. Using early eukaryotic ancestors (including LECA) as a test case, we assess the magnitude of bias and identify mechanistic bases of the estimation problems. Based on these results, we advocate the incorporation of contamination filtering as a routine step of reporting new draft genomes and caution against the outright interpretation of complex ancestral genomes and subsequent gene loss without accounting for contamination.
The genetic basis of wing spots inPieris canidiabutterflies
Authors: Wee Jocelyn Liang Qi , Murugesan Suriya Narayanan , Wheat Christopher , Monteiro Antónia
Published: November 2022

Spots in pierid butterflies and eyespots in nymphalid butterflies are likely non-homologous wing colour pattern elements, yet they share a few features in common. Both develop black scales that depend on the function of the genespalt, and both might have central signalling cells. This suggests that both pattern elements may be sharing common genetic circuitry. Hundreds of genes have already been associated with the development of nymphalid butterfly eyespot patterns, but the genetic basis of the simpler spot patterns on the wings of pierid butterflies has not been investigated. To facilitate studies of pierid wing patterns, we report a high-quality draft genome assembly forPieris canidia, the Indian cabbage white. We then conducted transcriptomic analyses of pupal wing tissues sampled from the spot and non-spot regions ofP. canidiaat 3-6h post-pupation. A total of 1352 genes were differentially regulated between wing tissues with and without the black spot, includingspalt, Krüppel-like factor 10, genes from the Toll, Notch, TGF-β, and FGFR signalling pathways, and several genes involved in the melanin biosynthetic pathway. We identified 21 genes that are up-regulated in both pierid spots and nymphalid eyespots and propose that spots and eyespots share regulatory modules despite their likely independent origins.
Geometry of visual working memory information in human gaze patterns
Authors: Linde-Domingo Juan , Spitzer Bernhard
Published: November 2022

Stimulus-dependent eye movements have been recognized as a potential confound in decoding visual working memory information from neural signals. Here, we combined eye-tracking with representational geometry analyses to uncover the very information in miniature gaze patterns while participants (n = 41) were cued to maintain visual object orientations. Although participants were discouraged from breaking fixation via real-time feedback, small gaze shifts (< 1 degree) robustly encoded the to-be-maintained stimulus orientation, with evidence for encoding two sequentially presented orientations at the same time. While the orientation encoding upon stimulus presentation was object-specific, it changed to a more object-independent format during cued maintenance, particularly when attention had been temporarily withdrawn from the memorandum. Finally, categorical reporting biases increased after unattended storage, with indications of biased gaze geometries emerging already during the maintenance periods prior to behavioral reporting. These findings disclose a wealth of information in gaze patterns during visuospatial working memory, and suggest systematic changes in representational format when memory contents have been unattended.
Crystal structure of anabolic steroid metabolite 4-chloroandrost-4-ene-3,17-dione
Authors: Nithimanon Saitarn , Sermmai Patpanat , Thongpanchang Chawanee , Saepua Siriporn , Thongpanchang Tienthong
Published: November 2022

The title compound, NorClAD, C18H23ClO2, a metabolite of an anabolic steroid norchlorotestosterone acetate (NClTA), was successfully synthesized. Its molecular structure was characterized by 1H NMR and 13C NMR spectroscopy and single-crystal X-ray diffraction. The positions of the chlorine substituent, carbonyl groups and the double bond, as well as the absolute configuration of the molecule, were established. A Hirshfeld surface analysis was performed.
Direct calculation of cryo-EM and crystallographic model maps for real-space refinement
Authors: Urzhumtsev Alexandre G. , Urzhumtseva Ludmila M. , Lunin Vladimir Y.
Published: November 2022

This work addresses the problem of the calculation of limited-resolution maps from an atomic model in cryo-electron microscopy and in X-ray and neutron crystallography, including cases where the resolution varies from one molecular region to another. Such maps are necessary in real-space refinement for comparison with the experimental maps. For an appropriate numeric comparison, the calculated maps should reproduce not only the structural features contained in the experimental maps but also the principal map distortions. These model maps can be obtained with no use of Fourier transforms but, similar to density distributions, as a sum of individual atomic contributions. Such contributions, referred to as atomic density images, are atomic densities morphed to reflect distortions of the experimental map, in particular the loss of resolution. They are described by functions composed of a central peak surrounded by Fourier ripples. For practical calculations, atomic images should be cut at some distance. It is shown that to reach a reasonable accuracy such a distance should be significantly larger than the distance customarily applied when calculating density distributions. This is a consequence of the slow rate with which the amplitude of the Fourier ripples decreases. Such a large distance means that at least a few ripples should be included in calculations in order to obtain a map that is sufficiently accurate. Oscillating functions describing these atomic contributions depend, for a given atomic type, on the resolution and on the atomic displacement parameter values. To express both the central peak and the Fourier ripples of the atomic images, these functions are represented by the sums of especially designed terms, each concentrated in a spherical shell and depending analytically on the atomic parameters. In this work, the strength of the dependence of the accuracy of resulting map on the accuracy of the atomic displacement parameters and on the truncation distance, i.e. the number of ripples included in atomic density images, is analyzed. This analysis is completed by practical aspects of the calculation of maps of inhomogeneous resolution. Tests show that the calculation of limited-resolution maps from an atomic model as a sum of atomic contributions requires a large truncation radius extending beyond the central peak of an atomic image and the first Fourier ripples. The article discusses the practical details of such calculations expressing atomic contributions as analytic functions of the atomic coordinates, the atomic displacement parameters and the local resolution.
Promise not kept: universal primary education for all children in sub-Saharan Africa
Authors: Fredriksen Birger
Published: November 2022

Purpose

This article examines why Universal Primary Education (UPE) has shifted from being a developing country challenge more broadly in the last half of the 20th century to become largely a sub-Saharan Africa (SSA) challenge today. It discusses a number of national and education sector system-wide challenges that have constrained the implementation of UPE in SSA more so than in other developing regions.

Design/methodology/approach

This article reviews the literature and policy documents on a wide range of developing country issues, and discusses why most SSA countries have faced unparalleled challenges in achieving UPE.

Findings

SSA governments should take the opportunity offered by their post-pandemic “build back better” efforts to fundamentally reset education policies to address the key causes of this major development failure. The overarching objective must be to develop education systems that are more inclusive, equitable and responsive to national development needs by better serving the large population groups, parts of society and economic sectors that currently derive little benefit from public education spending. This article highlights the urgency and challenges associated with achieving this objective.

Originality/value

Although the main responsibility lies with SSA governments, this paper stresses that the global community will be affected in many ways by how effectively this crisis is addressed. Therefore, this effort merits sustained global support including through more catalytic use of aid.
Towards a Paradigm Shift: How Can Machine Learning Extend the Boundaries of Quantitative Management Scholarship?
Authors: Valizade Danat , Schulz Felix , Nicoara Cezara
Published: November 2022

Management scholarship is beginning to grapple with the growing popularity of machine learning (ML) as an analytical tool. While quantitative research in our discipline remains heavily influenced by positivist thinking and statistical modelling underpinned by null hypothesis significance testing, ML is increasingly used to solve technical, computationally demanding problems. In this paper, we argue for a wider, more systematic adoption of the key tenets of ML in quantitative management scholarship, both in conjunction with and, where appropriate, as an alternative to canonical forms of statistical modelling. We discuss how ML can extend the boundaries of quantitative management scholarship, help management scholars to unpack complex phenomena, and improve the overall trustworthiness of quantitative research. The paper provides a representative review of the use of ML to date and uses a worked example to demonstrate the value of ML for management scholarship.
Are Reshoring Decisions Influenced by External Stakeholders and Country‐Level Environmental Regulation?
Authors: Sena Vania , Kanungo Rama Prasad , Ozdemir Sena , Yannopoulou Natalia , Patel Parth
Published: November 2022

The rationale behind reshoring activities remains unclear. Multinationals reshore their subsidiaries when regulations in the host country become too costly or difficult to manage. However, it is unclear whether the positive association between the propensity for reshoring subsidiaries and the host country's regulations applies to all types of subsidiaries (i.e. majority or minority owned) and whether it is moderated by other factors. We suggest that external stakeholders play a crucial role in strengthening the relationship between the decision to reshore and the host country's regulations. Within the context of international business, we examine the reshoring decision of a panel of subsidiaries controlled by UK multinationals located in 39 countries and focus on a specific set of environmental and corporate governance regulations. Our findings suggest that reshoring amongst minority‐owned subsidiaries is more likely to happen in countries with weak protection of shareholders and mandatory environmental disclosure. Such a relationship is also strengthened by the presence of external stakeholders, namely, foreign directors sitting on subsidiaries’ boards. We contribute to the reshoring literature by showing the role of external stakeholders and the impact of institutions and regulatory requirements on reshoring decisions.
TNM classification of malignant tumors: Eighth edition for retroperitoneal liposarcoma. Ways to improve
Authors: Nered Sergey N. , Volkov Alexander Yu. , Kozlov Nikolay A. , Stilidi Ivan S. , Arhiri Peter P.
Published: November 2022

Aim

This study was aimed at assessing the prognostic significance of the “TNM: Classification of Malignant Tumors” eighth edition (TNM8) in the most common retroperitoneal tumors ‐ liposarcoma.

Methods

The study included 192 patients with retroperitoneal liposarcoma (RLPS). The distribution of patients by stages and survival in accordance with the TNM8 were studied.

Results

In the TNM8, only the degree of malignancy of the tumor has a prognostic value. The T‐category does not reflect the actual size of the RLPS and is considered as T4 in 93%, which leads to inadequate staging. During the 15‐year period, there were no cases with stages II and IIIA, and the survival rate was estimated only in patients with stages I and IIIB. The tumor node metastasis (TNM) classification with new values of the T‐category was proposed by us, which demonstrated a more adequate distribution of patients by stages and the reliability of intergroup differences in the survival rate.

Conclusion

It is advisable to create a special TNM classification for RLPS, which makes up more than half of all retroperitoneal sarcomas. The TNM8 does not accurately reflect the prevalence of the tumor and the prognosis in RLPS. Revision of the T‐staging is necessary to improve the accuracy of the prognosis in RLPS. The modified by us TNM classification demonstrated a more adequate distribution of patients by stages.
The safety of tranexamic acid administration in total knee arthroplasty: a population‐based study from Taiwan
Authors: Hsu L.‐I. , Hsu H.‐W. , Chen J.‐W. , Wei S.‐T. , Hou S.‐M.
Published: November 2022

Tranexamic acid is an effective treatment to reduce blood loss. We performed a retrospective observational study to evaluate safety in unilateral total knee arthroplasty. We utilised Taiwan's national health insurance database to identify relevant patients and to retrieve information on peri‐operative blood transfusions and tranexamic acid administration within 60 days of follow‐up. We examined changes in the rate of transfusions and adverse events with respect to tranexamic acid administration using logistic regression. We observed a total of 226,719 knee arthroplasty cases during 2010–2019. Transfusion and tranexamic acid administration rates were 38.9% (88,258) and 42.9% (97,237), respectively. Tranexamic acid was associated with a 50% decrease in blood transfusions (RR: 0.50, 95%CI: 0.48–0.51). After propensity‐score matching, tranexamic acid was not associated with pulmonary embolism; deep vein thromboembolism; artery vein thromboembolism; acute myocardial infarction; ischaemic stroke; or in‐hospital mortality, but was significantly associated with acute kidney injury. Patients with existing chronic kidney disease suffered a high absolute risk of kidney injury irrespective of tranexamic acid administration (832 per 10,000, 95%CI 797–869). Tranexamic acid was also associated with surgical site infection. There was strong interaction between blood transfusion; tranexamic aid administration; and development of surgical site infection. In conclusion, tranexamic acid use was associated with decreased blood transfusion and was not associated with thromboembolic events. However, careful consideration is required before use in patients with pre‐existing renal disease. Further, our observed interaction between patients given tranexamic acid who subsequently require transfusion requires careful consideration with respect to enhanced prophylaxis against surgical site infection.
Pristinamycin‐induced toxic epidermal necrolysis: A case report
Authors: Ouni Bouraoui , Mansour Khadija , Slim Raoudha , Abdessayed Nihed , Bensayed Nesrine , Barka Malek , Fathallah Neila
Published: November 2022

Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute, life‐threatening and rare severe cutaneous adverse reactions induced by drugs in most cases. The drugs most often reported to be implicated in inducing TEN/SJS are allopurinol, antibacterial sulfonamides, antiepileptic drugs and oxicam. Pristinamycin is an oral streptogramin antibiotic with bactericidal activity against Gram‐positive bacteria that is rarely linked to TEN. Typically, this condition develops 4‐28 days after drug exposure, Herein, we report a case of a 71‐year‐old female who developed TEN within 3 days of administration of pristinamycin and was managed successfully with supportive care, including intravenous fluids, pain control, prophylactic antibiotics and intravenous methylprednisolone. This case of rapidly developing SJS/TEN after administration of pristinamycin highlights the possibility that these complications can develop within only a few days following ingestion of drugs thought to be probably safe.
Drug–drug interaction between rifabutin and dolutegravir: A population pharmacokinetic model
Authors: Kawuma Aida N. , Wasmann Roeland E. , Dooley Kelly E. , Maartens Gary , Denti Paolo
Published: November 2022

Rifampicin, a potent enzyme inducer, causes marked reduction of dolutegravir exposure. Rifabutin, a less potent enzyme inducer, may offer an alternative to rifampicin. We aimed to characterize the population pharmacokinetics of dolutegravir when co‐administered with rifabutin. We extended an existing dolutegravir model to include data from volunteers co‐administered with dolutegravir 50 mg and rifabutin 300 mg once daily. We ran simulations of dolutegravir with and without rifabutin co‐administration and compare dolutegravir trough concentrations with the IC90 and EC90 of 0.064 and 0.3 mg/L, respectively. Rifabutin decreased dolutegravir's volume of distribution by 33.1% (95% confidence interval 25.1%–42.3%) but did not affect the area under the concentration–time curve. Simulations showed that when 50 mg dolutegravir is co‐administered with rifabutin once daily, the probability to attain trough concentrations above the IC90 of 0.064 mg/L is more than 99%. Therefore, there is no need for dolutegravir dose adjustment. Rifabutin may offer an alternative to rifampicin for the treatment of HIV/tuberculosis co‐infected individuals.
Engaged followership and toxic science: Exploring the effect of prototypicality on willingness to follow harmful experimental instructions
Authors: Birney Megan E. , Reicher Stephen D. , Haslam S. Alexander , Steffens Niklas K. , Neville Fergus G.
Published: November 2022

Drawing on the ‘engaged followership’ reinterpretation of Milgram's work on obedience, four studies (three pre‐registered) examine the extent to which people's willingness to follow an experimenter's instructions is dependent on the perceived prototypicality of the science they are supposedly advancing. In Studies 1, 2 and 3, participants took part in a study that was described as advancing either ‘hard’ (prototypical) science (i.e., neuroscience) or ‘soft’ (non‐prototypical) science (i.e., social science) before completing an online analogue of Milgram's ‘Obedience to Authority’ paradigm. In Studies 1 and 2, participants in the neuroscience condition completed more trials than those in the social science condition. This effect was not replicated in Study 3, possibly because the timing of data collection (late 2020) coincided with an emphasis on social science's importance in controlling COVID‐19. Results of a final cross‐sectional study (Study 4) indicated that participants who perceived the study to be more prototypical of science found it more worthwhile, reported making a wider contribution by taking part, reported less dislike for the task, more happiness at having taken part, and more trust in the researchers, all of which indirectly predicted greater followership. Implications for the theoretical understanding of obedience to toxic instructions are discussed.
Aeolian sediment provenance and transport in the upper and middle reaches of the Yarlung Zangbo River, Tibet Plateau
Authors: Zhang Zhengcai , Ma Pengfei , La Zhen , Zhang Yan , Liang Aimin
Published: November 2022

Frequent and serious aeolian disasters occur in the upper and middle reaches of the Yarlung Zangbo River, which runs through the high‐elevation Tibet Plateau. Sediment geochemical characteristics can be used as a proxy to identify the sediment's provenance. To determine the provenance of aeolian sediments in the river's basin, we analysed major and trace element contents from surface samples and local clastic rocks throughout the basin. We found that the major and trace elements differed between the middle reaches, upper reaches and regions south of the river. Major element contents were similar in the upper and middle reaches, but trace elements differed. Al2O3, MgO and Na2O concentrations increased from the upper reaches to the lower reaches, and in the lower reaches, MgO and Na2O were enriched compared with the crustal average. The similarities between samples in the lower part of the upper reaches and those in the middle reaches indicated that sediment transported by fluvial systems from the upper reaches were first deposited in the wide valleys near Xigaze, where they formed a large area of shifting sand. These deposits were then transported by the wind to the river's middle reaches, where they formed a large area of shifting sand. When we compared aeolian sediment in the middle reaches with the local clastic rocks, they appeared to be unrelated. The difference between sediments south of the river and those in the middle reaches means that the southern sediments were not transported to the middle reaches. Therefore, the aeolian sediment in the middle reaches of the Yarlung Zangbo River mainly came from the lower part of the upper reaches, not from the local clastic rocks.