bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyramidal cell types drive functionally distinct cortical activity patterns during decision-making
Authors: Musall Simon , Sun Xiaonan R. , Mohan Hemanth , An Xu , Gluf Steven , Li Shujing , Drewes Rhonda , Cravo Emma , Lenzi Irene , Yin Chaoqun , Kampa Björn M. , Churchland Anne K.
Published: September 2021

Understanding how cortical circuits generate complex behavior requires investigating the cell types that comprise them. Functional differences across pyramidal neuron (PyN) types have been observed within cortical areas, but it is not known whether these local differences extend throughout the cortex, nor whether additional differences emerge when larger-scale dynamics are considered. We used genetic and retrograde labeling to target pyramidal tract (PT), intratelencephalic (IT) and corticostriatal projection neurons and measured their cortex-wide activity. Each PyN type drove unique neural dynamics, both at the local and cortex-wide scale. Cortical activity and optogenetic inactivation during an auditory decision task also revealed distinct functional roles: all PyNs in parietal cortex were recruited during perception of the auditory stimulus, but, surprisingly, PT neurons had the largest causal role. In frontal cortex, all PyNs were required for accurate choices but showed distinct choice-tuning. Our results reveal that rich, cell-type-specific cortical dynamics shape perceptual decisions.
Fragile X syndrome patient-derived neurons developing in the mouse brain show FMR1 -dependent phenotypes
Authors: Krzisch Marine A. , Wu Hao , Yuan Bingbing , Whitfield Troy W. , Shawn Liu X. , Fu Dongdong , Shih Jennifer , Garrett-Engele Carrie M. , Chang Aaron N. , Warren Stephen , Cacace Angela , Andrykovich Kristin R. , Rietjens Rosalie G. J. , Jain Bhav , Wallace Owen , Sur Mriganka , Jaenisch Rudolf
Published: September 2021

Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The transplanted cells populated the brain and a proportion differentiated into neurons and glial cells. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons after an initial delay. Additionally, increased percentages of Arc- and Egr1-positive FXS neurons and wider dendritic protrusions of mature FXS striatal medium spiny neurons pointed to an increase in synaptic activity and synaptic strength as compared to control. This transplantation approach provides new insights into the alterations of neuronal development in FXS by facilitating physiological development of cells in a 3D context, and could be used to test new therapeutic compounds correcting neuronal development defects in FXS.
Global Metabolome Analysis of Dunaliella tertiolecta, Phaeobacter italicus R11 Co-cultures using Thermal Desoprtion - Comprehensive Two-dimensional Gas Chromatography - Time-of-Flight Mass Spectrometry (TD-GC×GC-TOFMS)
Authors: Armstrong Michael D. Sorochan , Arredondo Campos René Oscar , Bannon Catherine C. , de la Mata A. Paulina , Case Rebecca J. , Harynuk James J.
Published: September 2021

Dunaliella tertiolecta is a marine microalgae that has been studied extensively as a potential carbon-neutral biofuel source [1]. Microalgae oil contains high quantities of energy-rich fatty acids and lipids, but is not yet commercially viable as an alternative fuel. Carefully optimised growth conditions, and more recently, algal-bacterial co-cultures have been explored as a way of improving the yield of Dunaliella tertiolecta microalgae oils. The relationship between the host microalgae and bacterial co-cultures is currently poorly understood. Here, a complete workflow is proposed to analyse the global metabolomic profile of co-cultured Dunaliella tertiolectra and Phaeobacter italicus R11, which will enable researchers to explore the chemical nature of this relationship in more detail.

Graphical Abstract

Highlights

A method for direct microalgae sample introduction is proposed.

Advanced chemometric tools can extract, useful and discriminating metabolomic features even from very noisy complex datasets.
Role of type I interferon signaling and microglia in the abnormal long term potentiation and object place recognition deficits of male mice with a mutation of the Tuberous Sclerosis 2 gene
Authors: López-Aranda Manuel F. , Boxx Gayle M. , Phan Miranda , Bach Karen , Mandanas Rochelle , Herrera Isaiah , Taloma Sunrae , Thadani Chirag , Lu Odilia , Bui Raymond , Liu Shuhan , Li Nan , Zhou Yu , Cheng Genhong , Silva Alcino J.
Published: September 2021

Tuberous Sclerosis Complex (TSC) is a genetic disorder associated with high rates of intellectual disability and autism. Although previous studies focused on the role of neuronal deficits in the memory phenotypes of rodent models of TSC, the results presented here demonstrate a role for microglia in these deficits. Mice with a heterozygous null mutation of the Tsc2 gene (Tsc2+/-), show deficits in hippocampal dependent tasks, as well as abnormal long-term potentiation (LTP) in the hippocampal CA1 region. Here, we show that microglia and type I interferon signaling (IFN1) have a key role in the object place recognition (OPR; a hippocampal dependent task) deficits and abnormal LTP of Tsc2+/-male mice. Unexpectedly, we demonstrate that male, but not female, Tsc2+/-mice showed OPR deficits. Importantly, these deficits can be rescued by depletion of microglia, as well as by a genetic manipulation of a signaling pathway known to modulate microglia function (interferon-alpha/beta receptor alpha chain null mutation). In addition to rescuing the OPR deficits, depletion of microglia also reversed the abnormal LTP of the Tsc2+/-mice. Altogether, our results suggest that altered IFN1 signaling in microglia cause the abnormal LTP and OPR deficits of male Tsc2+/-mice.
Spatiotemporal co-dependency between macrophages and exhausted CD8+T cells in cancer
Authors: Kersten Kelly , Hu Kenneth H. , Combes Alexis J. , Samad Bushra , Harwin Tory , Ray Arja , Rao Arjun Arkal , Cai En , Marchuk Kyle , Artichoker Jordan , Courau Tristan , Shi Quanming , Belk Julia , Satpathy Ansuman T. , Krummel Matthew F.
Published: September 2021

T cell exhaustion is a major impediment to anti-tumor immunity. However, it remains elusive how other immune cells in the tumor microenvironment (TME) contribute to this dysfunctional state. Here we show that the biology of tumor-associated macrophages (TAM) and exhausted T cells (Tex) in the TME is extensively linked. We demonstrate thatin vivodepletion of TAM reduces exhaustion programs in tumor-infiltrating CD8+T cells and reinvigorates their effector potential. Reciprocally, transcriptional and epigenetic profiling reveals that Texexpress factors that actively recruit monocytes to the TME and shape their differentiation. Using lattice light sheet microscopy, we show that TAM and CD8+T cells engage in unique long-lasting antigen-specific synaptic interactions that fail to activate T cells, but prime them for exhaustion, which is then accelerated in hypoxic conditions. Spatially resolved sequencing supports a spatiotemporal self-enforcing positive feedback circuit that is aligned to protect rather than destroy a tumor.

Graphical Abstract
Interactions of cytosolic termini of the Jen1 monocarboxylate transporter are critical for trafficking, transport activity and endocytosis
Authors: Barata-Antunes Cláudia , Talaia Gabriel , Broutzakis George , Ribas David , De Beule Pieter , Casal Margarida , Stefan Christopher J. , Diallinas George , Paiva Sandra
Published: September 2021

Plasma membrane (PM) transporters of the major facilitator superfamily (MFS) are essential for cell metabolism and growth, as well as for survival in response to stress or cytotoxic drugs, in both prokaryotes and eukaryotes. In the yeast Saccharomyces cerevisiae, Jen1 is a monocarboxylate/H+ symporter that has been used to dissect the molecular details underlying control of cellular expression, transport mechanism and turnover of MFS transporters. Here, we present evidence supporting previously non-described roles of the cytosolic N- and C- termini in Jen1 biogenesis, PM stability and activity, through functional analyses of rationally designed truncations and chimeric constructs with UapA, a S. cerevisiae endocytosis-insensitive purine transporter from Aspergillus nidulans. Our results reveal a cryptic role of the N-terminal region and thus show that both cytosolic N- and C-termini are critical for Jen1 trafficking to the PM, transport activity and endocytosis. In particular, we provide evidence that the N- and the C-cytosolic termini of Jen1 undergo transport-dependent dynamic intra-molecular interactions, which critically affect the mechanism of transport and turnover of Jen1. Our results support an emerging concept where the cytosolic tails of PM transporters control transporter expression and function, through flexible intra-molecular interactions with each other and the transmembrane core of the protein. This idea may be extended to other MFS members providing a deeper understanding of conserved, but also evolving, mechanisms underlying MFS transporter structure-function relationships.
Community assessment of crustose calcifying red algae as coral recruitment substrates
Authors: Deinhart Mari E. , Mills Matthew S. , Schils Tom
Published: September 2021

Successful recruitment of invertebrate larvae to reef substrates is essential to the health of tropical coral reef ecosystems and their capacity to recover from disturbances. Crustose calcifying red algae (CCRA) have been identified as important recruitment substrates for scleractinian corals. As such, CCRA as a whole or subgroups (e.g., crustose coralline algae, CCA) are often used at the functional group level in experimental, ecological, and monitoring studies. Species of CCRA, however, differ in their ecological roles and their value as coral recruitment substrates. Here, we (1) investigate the species richness and community composition of CCRA on experimental coral recruitment tiles, and (2) assess if there is a recruitment preference of the coralAcropora surculosafor any of these CCRA species. 27 species of two orders of CCRA (Corallinales and Peyssonneliales) were identified from the recruit tiles. None of the DNA sequences of these species matched released sequences in GenBank or sequences of CCRA collected from natural reef systems in Guam. The similarity in CCRA communities between the recruitment tiles was high. Two species of CCRA were significantly preferred as recruitment substrates over the other CCRA species. Both of these species belonged to the subfamily of the Lithophylloideae. These two species are closely related to Pacific species that have been referred to asTitanoderma-but probably have to be assigned to another genus- and many of the latter have been attributed to be preferred coral recruitment substrates. Of all CCRA, Lithophylloideae sp. 1 had the highest benthic cover on the recruitment tiles and was the most preferred recruitment substrate. These findings highlight the high taxonomic diversity of CCRA communities and provide insight into species-specific ecological roles of CCRA that are often overlooked.
HSD11β1 promotes EMT-mediated breast cancer metastasis
Authors: Nakayama Joji , Ishikawa Takamasa , Nishimura Tatsunori , Yamanaka Sanae , Gotoh Noriko , Yamauchi Chisako , Ohnishi Tatsuya , Soga Tomoyoshi , Fujii Satoshi , Makinoshima Hideki
Published: September 2021

Abnormal biosyntheses of steroid hormones and dysregulation of steroid hormone receptors contribute to breast cancer metastasis but the mechanisms of that are poorly understand. Here we report a stress hormone producing enzyme, Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11β1) promotes breast cancer metastasis. HSD11β1 was ectopically expressed in seventy-one percent of triple-negative breast tumors and correlated with shorter overall survival. HSD11β1 significantly promoted breast cancer metastasis through induction of epithelial-to-mesenchymal transition (EMT); conversely, pharmacologic and genetic inhibition of HSD11β1 suppressed metastatic progression of breast cancer cells. Moreover, 11-hydroxyprogesterone (11-OHP) whom HSD11β1 produced in breast cancer cells, conferred metastatic properties on non-metastatic breast cancer cells through induction of EMT. We identified Peroxisome Proliferator-activated Receptor Alpha (PPAR-α) as essential for both HSD11β1 and 11OHP-driven EMT. Knockdown of PPAR-α induced MET on HSD11β1-expressing breast cancer cells. Taken together, HSD11β1 promotes breast cancer metastasis and would be a novel target for suppressing breast cancer metastasis.
Analysis of the ARTIC version 3 and version 4 SARS-CoV-2 primers and their impact on the detection of the G142D amino acid substitution in the spike protein
Authors: Davis James J. , Long S. Wesley , Christensen Paul A. , Olsen Randall J. , Olson Robert , Shukla Maulik , Subedi Sishir , Stevens Rick , Musser James M.
Published: September 2021

The ARTIC Network provides a common resource of PCR primer sequences and recommendations for amplifying SARS-CoV-2 genomes. The initial tiling strategy was developed with the reference genome Wuhan-01, and subsequent iterations have addressed areas of low amplification and sequence drop out. Recently, a new version (V4) was released, based on new variant genome sequences, in response to the realization that some V3 primers were located in regions with key mutations. Herein, we compare the performance of the ARTIC V3 and V4 primer sets with a matched set of 663 SARS-CoV-2 clinical samples sequenced with an Illumina NovaSeq 6000 instrument. We observe general improvements in sequencing depth and quality, and improved resolution of the SNP causing the D950N variation in the spike protein. Importantly, we also find nearly universal presence of spike protein substitution G142D in Delta-lineage samples. Due to the prior release and widespread use of the ARTIC V3 primers during the initial surge of the Delta variant, it is likely that the G142D amino acid substitution is substantially underrepresented among early Delta variant genomes deposited in public repositories. In addition to the improved performance of the ARTIC V4 primer set, this study also illustrates the importance of the primer scheme in downstream analyses.

Importance

ARTIC Network primers are commonly used by laboratories worldwide to amplify and sequence SARS-CoV-2 present in clinical samples. As new variants have evolved and spread, it was found that the V3 primer set poorly amplified several key mutations. In this report, we compare the results of sequencing a matched set of samples with the V3 and V4 primer sets. We find that adoption of the ARTIC V4 primer set is critical for accurate sequencing of the SARS-CoV-2 spike region. The absence of metadata describing the primer scheme used will negatively impact the downstream use of publicly available SARS-Cov-2 sequencing reads and assembled genomes.
Heterologous expression of the human ZIP4 zinc transporter in Saccharomyces cerevisiae
Authors: Liu Yuting , Bafaro Elizabeth M. , Dempski Robert E.
Published: September 2021

The human (h) transporter, hZIP4 is the primary zinc importer in the intestine and is also expressed in a variety of organs such as the pancreas and brain. Dysfunction of hZIP4 can result in the zinc deficiency disease acrodermatitis enteropathica (AE), which disrupts digestive and immune system homeostasis. Structure-function studies of hZIP4 have been greatly hindered by the absence of a robust heterologous expression system. Here, we report the heterologous expression of hZIP4 in Saccharomyces cerevisiae. Both a wild type and a mutant S. cerevisiae strain, in which the endogenous zinc transporters are deleted, were used to test the expression and localization of an hZIP4-GFP fusion protein. A full-length hZIP4-GFP and a truncated membrane domain only (mhZIP4-GFP) protein were successfully produced and targeted to the plasma membrane in yeast.
Cardenolide Increase in Foxglove During Stresses Corresponds to Cholesterol and Phytosterol Biosynthesis
Authors: Raghavan Indu , Ravi Baradwaj G. , Carroll Emily , Wang Zhen Q.
Published: September 2021

Cardenolides are a group of steroidal metabolites found in Digitalis lanata with potent cardioactive effects on animals. In plants, cardenolides are involved in various stress responses. However, the molecular mechanism of cardenolide increase during stresses is mostly unknown. Here we show that cardenolides were increased upon methyl jasmonate (MJ), sorbitol, potassium (KCl) chloride, and salicylic acid analog (BTH: 2,1,3-benzothiadiazole) treatments. However, the expression of three known genes for cardenolide biosynthesis did not correlate well with these increases. Specifically, the expression of progesterone-5β-reductases (P5βR and P5βR2) did not correlate with cardenolide increase. The expression of 3β-hydroxysteroid dehydrogenase (3βHSD) correlated with cardenolide levels only during the BTH treatment. Mining the D. lanata transcriptome identified genes involved in cholesterol and phytosterol biosynthesis: SSR1 (sterol sidechain reductase), SMO1, and SMO3 (sterol methyl oxidase). Surprisingly, the expression of all three genes correlated well with the cardenolide increase after BTH treatment. Phylogenetic analysis showed that SSR1 is likely involved in both cholesterol and phytosterol biosynthesis. In addition, SMO1 is likely specific to phytosterol biosynthesis, and SMO3 is specific to cholesterol biosynthesis. These results suggest that both cholesterol and phytosterol are involved in cardenolide biosynthesis. In summary, this work shows that cardenolides are important for stress responses in D. lanata and revealed a novel relationship between phytosterol and cardenolide biosynthesis.
Intergenerational hormesis is regulated by heritable 18S rRNA methylation
Authors: Liberman Noa , Gerashchenko Maxim V. , Boulias Konstantinos , MacWhinnie Fiona G , Ying Albert Kejun , Taylor Anya Flood , Al Haddad Joseph , Shibuya Hiroki , Roach Lara , Dong Anna , Gladyshev Vadim N. , Greer Eric Lieberman
Published: September 2021

Heritable non-genetic information can regulate a variety of complex phenotypes. However, what specific non-genetic cues are transmitted from parents to their descendants are poorly understood. Here, we perform metabolic methyl-labelling experiments to track the heritable transmission of methylation from ancestors to their descendants in the nematode Caenorhabditis elegans. We find that methylation is transmitted to descendants in proteins, RNA, DNA and lipids. We further find that in response to parental starvation, fed naïve progeny display reduced fertility, increased heat stress resistance, and extended longevity. This intergenerational hormesis is accompanied by a heritable increase in N6’-dimethyl adenosine (m6,2A) on the 18S ribosomal RNA at adenosines 1735 and 1736. We identified the conserved DIMT-1 as the m6,2A methyltransferase in C. elegans and find that dimt-1 is required for the intergenerational hormesis phenotypes. This study provides the first labeling and tracking of heritable non-genetic material across generations and demonstrates the importance of rRNA methylation for regulating the heritable response to starvation.
Omics profiling identifies MAPK/ERK pathway as a gatekeeper of nephron progenitor metabolism
Authors: Kwon Hyuk Nam , Kurtzeborn Kristen , Jin Xing , Loh Abigail , Escande-Beillard Nathalie , Reversade Bruno , Park Sunghyouk , Kuure Satu
Published: September 2021

Nephron endowment is defined by fetal kidney growth and critically dictates renal health in adults. Despite the advances in understanding the molecular regulation of nephron progenitors, the causes for low congenital nephron count and contribution of basic metabolism to nephron progenitor biology remain poorly understood. Here we characterized the metabolic consequences of MAPK/ERK-deficiency in nephron progenitors, whose maintenance and propagation in developing kidney critically depends on ERK activation. Our LC/MS-based metabolomics profiling identified 42 reduced metabolites, of which 26 were further supported by in vivo transcriptional characterization of MAPK/ERK-deficient nephron progenitors. This revealed a severe shortage of energy and nucleotide biosynthesis precursors, blockage in glycolysis and diminished pyruvate and proline metabolism. Utilization of in vitro kidney cultures demonstrated a dosage-specific function for glycolytic pyruvate as an energy source that controls the shape of the ureteric bud tip kwon to serve as a niche for nephron progenitor regulation. Analysis of the proline biosynthesis effects in developing kidney in vivo revealed premature loss of nephron progenitor maintenance in the absence of Pycr1/2 functions. Our results suggest that MAPK/ERK-dependent nephron progenitor metabolism functionally contributes to progenitor preservation by controlling pyruvate availability and proline metabolism in developing kidneys.
Gene expression phylogenies and ancestral transcriptome reconstruction resolves major transitions in the origins of pregnancy
Authors: Mika Katie , Whittington Camilla M. , McAllan Bronwyn M. , Lynch Vincent J.
Published: September 2021

Structural and physiological changes in the female reproductive system underlie the origins of pregnancy in multiple vertebrate lineages. In mammals, for example, the glandular portion of the lower reproductive tract has transformed into a structure specialized for supporting fetal development. These specializations range from relatively simple maternal provisioning in egg-laying monotremes to an elaborate suite of traits that support intimate maternal-fetal interactions in Eutherians. Among these traits are the maternal decidua and fetal component of the placenta, but there is considerable uncertainty about how these structures evolved. We identified the origins of pregnancy utilizing ancestral transcriptome reconstruction to infer functional evolution of the maternal-fetal interface. Remarkably, we found that maternal gene expression profiles are correlated with degree of placental invasion. These results indicate that an epitheliochorial-like placenta evolved early in the mammalian stem-lineage and that the ancestor of Eutherians had a hemochorial placenta, and suggest maternal control of placental invasiveness. Collectively, these data resolve major transitions in the evolution of pregnancy and indicate that ancestral transcriptome reconstruction can be used to study the function of ancestral cell, tissue, and organ systems.
mSOD1-NSG mice: a new in vivo model to test human T cells in ALS
Authors: Graber David J , Sentman Marie-Louise , Cook W. James , Sentman Charles L
Published: September 2021

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with unclear etiology and few treatment options. Engineering of human cells for therapy has great potential to provide a means to create long-lived therapeutics that can respond to local signals within tissues. One challenge for development of human cell therapeutics is to have disease models that do not reject transplanted human cells. G93A mutant superoxide dismutase-1 (mSOD1) transgenic mouse model is a robust disease model for ALS, with development of local inflammation, activation of microglia and astrocytes, motor neuron death, and development of paralysis. To create a mouse model for ALS that permits the transplantation of human T cells without immune-mediate rejection, we bred the G93A transgene onto the NOD-SCID-IL-2Rγ-deficient (NSG) mouse model to create mSOD1-NSG mice. We report that mSOD1-NSG mice develop a progressive ALS-like disease with microgliosis, astrogliosis, and paralysis development with an average onset at 11 weeks and end-stage at 14 weeks. Transplanted human T regulatory cells survive in these mice for at least 60 days. This mSOD1-NSG mouse model for ALS can be used to test human T cell-based therapeutics, and it may be helpful to test any human cell-based therapy for ALS.

Significance Statement

G93A SOD1 transgenic NSG mice develop a progressive ALS-like disease and are an in vivo model for testing human T cell-based therapies for ALS.
The cytokine receptor DR3 identifies and activates thymic NKT17 cells
Authors: Luo Shunqun , Liman Nurcin , Crossman Assiatu , Park Jung-Hyun
Published: September 2021

Invariant natural killer T (iNKT) cells are thymus-generated T cells with innate-like characteristics and effector function. Several functionally distinct iNKT subsets have been identified, but NKT17 is the only iNKT subset that produces the proinflammatory cytokine IL-17. NKT17 cells are generated in the thymus and then exported into the periphery to populate lymphoid organs and barrier tissues, such as the lung, to provide critical support in host defense. However, the molecular mechanisms that drive the thymic development and subset-specific activation of NKT17 cells remain mostly unknown. Here, we identify the cytokine receptor DR3, a member of the TNF receptor superfamily, being selectively expressed on NKT17 cells but absent on all other thymic iNKT subsets. We further demonstrate that DR3 ligation leads to the in vivo activation of thymic NKT17 cells and provides in vitro costimulatory effects upon α-GalCer-stimulation. Thus, our study reports the identification of a specific surface marker for thymic NKT17 cells that selectively triggers their activation both in vivo and in vitro. These findings provide new insights for deciphering the role and function of IL-17-producing NKT17 cells and for understanding the development and activation mechanisms of iNKT cells in general.
The short flagella 1 (SHF1) gene in Chlamydomonas encodes a Crescerin TOG-domain protein required for late stages of flagellar growth
Authors: Perlaza Karina , Mirvis Mariya , Ishikawa Hiroaki , Marshall Wallace
Published: September 2021

Length control of flagella represents a simple and tractable system to investigate the dynamics of organelle size. Models for flagellar length control in the model organism, Chlamydomonas reinhardtii have focused on the length-dependence of the intraflagellar transport (IFT) system which manages the delivery and removal of axonemal subunits at the tip of the flagella. One of these cargoes, tubulin, is the major axonemal subunit, and its frequency of arrival at the tip plays a central role in size control models. However, the mechanisms determining tubulin dynamics at the tip are still poorly understood. We discovered a loss-of-function mutation that leads to shortened flagella, and found that this was an allele of a previously described gene, SHF1, whose molecular identity had not previously been determined. We found that SHF1 encodes a Chlamydomonas ortholog of Crescerin, previously identified as a cilia-specific TOG-domain array protein that can bind tubulin via its TOG domains and increase tubulin polymerization rates. In this mutant, flagellar regeneration occurs with the same initial kinetics as wild-type cells, but plateaus at a shorter length. Using a computational model in which the flagellar microtubules are represented by a differential equation for flagellar length combined with a stochastic model for cytoplasmic microtubule dynamics, we found that our experimental results are best described by a model in which Crescerin/SHF1 binds tubulin dimers in the cytoplasm and transports them into the flagellum. We suggest that this TOG-domain protein is necessary to efficiently and preemptively increase intra-flagella tubulin levels to offset decreasing IFT cargo at the tip as flagellar assembly progresses.
Construction of multicellular yeast networks using the communication toolkit with variable specificity and attenuation
Authors: Krink Nicolas , Loechner Anne C. , Anders Alexander , Kahnt Jörg , Rensing Stefan , Hochberg Georg , Sourjik Victor
Published: September 2021

The key next step in synthetic biology is to extend cellular network engineering to the multicellular level by utilizing cell-cell communication for information processing. To facilitate the implementation of multicellular networks in the most commonly used eukaryotic chassis, Saccharomyces cerevisiae, we developed the yeast communication toolkit (YCTK). This toolkit is based on the fungal mating pathway and contains five pheromone-inducible promoters (response parts), eleven pheromones (α-factors; sender parts), eleven pheromone receptors (Ste2; receiver parts), as well as five Bar1 proteases (suppressor parts). All YCTK parts were thoroughly characterized and are compatible with the commonly used yeast Golden Gate cloning standard. We demonstrated the application of the YCTK by implementing several different logic gate-like population networks. Furthermore, we used this toolkit to investigate the pheromone-receptor promiscuity patterns among different yeast species. This toolkit extends currently available resources for construction of complex multicellular eukaryotic networks with varying degrees of promiscuity and attenuation.
Evolutionary dynamics ofBegomovirusescausing Papaya leaf curl disease in India
Authors: Srivasatava Aarshi , Pandey Vineeta , Sahu Anurag Kumar , Yadav Dinesh , Gaur R.K.
Published: September 2021

The genusbegomovirusrepresents a group of multipartite viruses that significantly damages many agricultural crops, including papaya and drastically influence the overall production. Understanding the genetic variations, mutations and recombination of thebegomoviruspopulation infecting papaya has several important implications in alleviating substantial losses, mainly in developing countries, including India. In an attempt for a bioinformatics driven study of diversity and variability of papaya leaf curl disease in India, a total of thirty-two (32) DNA-A and sixteen (16) betasatellite sequences were retrieved from GenBank. An uneven distribution of evolutionary divergence has been observed across the branch length, which triggered the estimated recombinational event. Interestingly, a maximum of thebegomoviruseswere found to be intra-species recombinants. Further genetic variability, selection pressure, and substitution rate acting on the population were estimated and found to be high enough to support the evolution of geminiviruses. Genetic divergence composition in allbegomovirusdatasets revealed predominance of nucleotide diversity driven by mutation. The analysis indicates that even though a significant fraction of the genetic variations might be due to recombination but, it was constantly lower than the mutation rate. Thus, the diversification of thebegomoviruspopulation is principally impelled by mutational dynamics.
Phosphorus uptake and toxicity is delimited by mycorrhizal symbiosis in P-sensitive Eucalyptus marginata but not in P-tolerant Acacia celastrifolia
Authors: Tibbett Mark , Daws Matthew I. , Ryan Megan H.
Published: September 2021

Many plant species from regions with ancient, highly-weathered nutrient-depleted soils have specialised adaptations for acquiring P and are sensitive to excess P-supply. Mycorrhizal associations may regulate P-uptake at high external P-concentrations, potentially reducing P-toxicity. We predicted that excess P-application will negatively impact species from the nutrient-depleted jarrah forest of Western Australia and that mycorrhizal inoculation will reduce P-toxicity by regulating P-uptake. For seedlings of the N2-fixing legume Acacia celastrifolia and the tree species Eucalyptus marginata, we measured growth at P-concentrations of 0 to 90 mg kg−1 soil and in relation to inoculation with the arbuscular mycorrhizal fungus (AMF) Rhizophagus irregularis. Non-inoculated A. celastrifolia maintained leaf P-concentrations at <2 mg g−1 dry mass (DM) across the range of external P-concentrations. However, for non-inoculated E. marginata, as external P-concentrations increased leaf P also increased, reaching >9 mg g−1 DM at 30 mg P kg−1 soil. A. celastrifolia DM increased with increasing external P-concentrations, while E. marginata DM was maximal at 15 mg P kg−1 soil, declining at higher external P concentrations. Neither DM nor leaf P of A. celastrifolia were affected by inoculation with AMF. For E. marginata, even at 90 mg P kg−1 soil, inoculation with AMF resulted in leaf P remaining <1 mg g−1 DM, and DM being maintained. These data strengthen the evidence base that AMF may not only facilitate P-uptake at low external P-concentrations, but are also important for moderating P-uptake at elevated external P-concentrations and maintaining plant P concentrations within a relatively narrow concentration range.
Drivers of sustainable healthcare supply chain performance: multi-criteria decision-making approach under grey environment
Authors: Hossain Md Kamal , Thakur Vikas
Published: September 2021

Purpose

This paper aims to explore the drivers of sustainable healthcare supply chain (SHCSC) performance measurement through extensive literature review and experts' opinions. The drivers are then scrutinized and their priority vector is calculated to provide quality and cost-effective healthcare supply chain (HCSC) services.

Design/methodology/approach

The drivers of the SHCSC performance measurement are validated using the grey-Delphi technique. After validating the drivers, they are prioritized using the grey-analytic hierarchy process (G-AHP), a multi-criteria decision-making tool.

Findings

The findings of the study highlight the prioritized drivers based on the preferences given by the experts. The findings of the study highlight the most prioritized drivers of healthcare (HC) by-product management system, coordinating and facilitating green suppliers in the HCSC and green packaging of pharmaceutical as well as other essential items.

Practical implications

The HCSC managers should coordinate with all the stakeholders across the supply chain and involve them in the decision-making process to make products and services greener and become complicit in complying with the sustainable policy guidelines. The study highlights the strategic policy and managerial implications for implementing sustainability in the HCSC.

Originality/value

The validation and prioritization of the drivers of SHCSC in developing nations' contexts is the key contribution of the study. Grey-AHP enables a practical approach towards enhancing the sustainability of the HCSC and opening the doors for generalizing the study for future research works.
Product eco-design practice in green supply chain management: a China-global examination of research
Authors: Li Jingjing , Sarkis Joseph
Published: September 2021

Purpose

This paper comprehensively and systematically reviews and critiques the product eco-design practice in green supply chain management studies. It seeks to explore drivers, barriers and initiatives of eco-design practice with a specific emphasis on China in comparison to non-China countries.

Design/methodology/approach

This paper adopts a systematic literature review approach. It also uses a conceptual thematic landscape of the global eco-design practice along supply chains to critically evaluate published studies. The Web of Science™ Core Collection database is used as the source.

Findings

Results show that although common factors exist, China exhibits a higher number of barriers, leading to an overall lag in eco-design adoption. China’s advantage lies in pressing market demand, actively engaged human resources and a cooperative culture. Alternatively, non-China countries demonstrate their relative superiority in eco-design tools, knowledge and innovation. Findings also indicate stakeholders simultaneously act as the three roles of eco-design practice in all countries, so do environmental regulations in China.

Originality/value

A thematic framework is introduced that can be used to further investigate and identify research opportunities. This study aids practitioners take stock of current eco-design management issues. It also includes pertinent recommendations on international eco-design performance improvement. It especially provides significant insights into successful eco-design implementation to green supply chains in China.
Mblk‐1 regulates sugar responsiveness in honey bee (Apis mellifera) foragers
Authors: Liu Fang , Wu Lixian , Zhang Yuan , Li Qiang , Li Liangbin , Huang Zachary Y. , Zhao Hongxia
Published: September 2021

Brain transcriptional regulatory network for behavior demonstrates that brain gene expression in the honey bee can be accurately predicted from the expression transcription factors (TFs), but roles for specific TFs are less understood. Mushroom bodies (MBs) are important for learning, memory and sensory integration in the honey bee brain. A TFs, Mblk‐1, expressed preferentially in the large‐type Kenyon cells of the honeybee MBs is predicted to be involved in brain function by regulating transcription of its target genes in honey bee. However, its function and the mechanism of regulation in behavior of honey bee is still obscure. Here we show that Mblk‐1 had significantly higher expression in the brains of forager bees relative to nurse bees. Mblk‐1 was significantly inhibited in bees fed small interfering RNA. In addition, inhibition of Mblk‐1 decreased sucrose responsiveness in foragers. Finally, we determined that Mblk‐1 regulated the messenger RNA of AmGR1. These findings suggest that Mblk‐1 may target AmGR1 to regulate the sucrose responsiveness of foragers.
Performance and automation of ancient DNA capture with RNA hyRAD probes
Authors: Suchan Tomasz , Kusliy Mariya A. , Khan Naveed , Chauvey Loreleï , Tonasso‐Calvière Laure , Schiavinato Stéphanie , Southon John , Keller Marcel , Kitagawa Keiko , Krause Johannes , Bessudnov Alexander N. , Bessudnov Alexander A. , Graphodatsky Alexander S. , Valenzuela‐Lamas Silvia , Wilczyński Jarosław , Pospuła Sylwia , Tunia Krzysztof , Nowak Marek , Moskal‐delHoyo Magdalena , Tishkin Alexey A. , Pryor Alexander J. E. , Outram Alan K. , Orlando Ludovic
Published: September 2021

DNA hybridization‐capture techniques allow researchers to focus their sequencing efforts on preselected genomic regions. This feature is especially useful when analysing ancient DNA (aDNA) extracts, which are often dominated by exogenous environmental sources. Here, we assessed, for the first time, the performance of hyRAD as an inexpensive and design‐free alternative to commercial capture protocols to obtain authentic aDNA data from osseous remains. HyRAD relies on double enzymatic restriction of fresh DNA extracts to produce RNA probes that cover only a fraction of the genome and can serve as baits for capturing homologous fragments from aDNA libraries. We found that this approach could retrieve sequence data from horse remains coming from a range of preservation environments, including beyond radiocarbon range, yielding up to 146.5‐fold on‐target enrichment for aDNA extracts showing extremely low endogenous content (<1%). Performance was, however, more limited for those samples already characterized by good DNA preservation (>20%–30%), while the fraction of endogenous reads mapping on‐ and off‐target was relatively insensitive to the original endogenous DNA content. Procedures based on two instead of a single round of capture increased on‐target coverage up to 3.6‐fold. Additionally, we used methylation‐sensitive restriction enzymes to produce probes targeting hypomethylated regions, which improved data quality by reducing post‐mortem DNA damage and mapping within multicopy regions. Finally, we developed a fully automated hyRAD protocol utilizing inexpensive robotic platforms to facilitate capture processing. Overall, our work establishes hyRAD as a cost‐effective strategy to recover a set of shared orthologous variants across multiple ancient samples.
Children & Migration: Political Constructions and Contestations
Authors: Pruitt Lesley J.
Published: September 2021

This article demonstrates the importance of paying attention to the roles children and childhood play in policy making relating to migration, especially since the outcomes of these debates have serious implications for children and for migrants, refugees, and asylum seekers of all ages. The article considers a case study examining political representations of migrant, asylum seeker, and refugee children from 2015 to 2016 in the United Kingdom Parliament. Applying discourse analysis to Hansard records, the article demonstrates how across significant political differences, policy makers come together in painting children as victims in need of urgent protection while situating themselves and the UK as best placed to determine how to provide this security to the children in question – historically, currently, and in the future. In doing so, policy makers contribute to inaccurate essentialisations of children, and simultaneously situate the UK as a global protector of children, even when limited agreement on policy approaches exists.
Increased carbohydrate antigen 19‐9 expression in a thymic neuroendocrine tumor
Authors: Shimizu Yuki , Kanda Shintaro , Fukushima Toshirou , Kobayashi Takashi , Kondo Ryoichi , Koizumi Tomonobu
Published: September 2021

Here, we report a case of carbohydrate antigen (CA) 19‐9‐producing mediastinal neuroendocrine tumor (NET) (atypical carcinoid). A 54‐year‐old woman with no specific relevant medical history was referred to our hospital because of increased CA19‐9 (95.3 U/ml) detected on health screening. Chest computed tomography (CT) revealed an anterior mediastinal mass without localized lymphadenopathy. Thoracic surgery was performed and the histopathological diagnosis was thymic CA19‐9‐positive NET. The patient developed mediastinal lymph node metastasis at 1 year (CA19‐9: 413 U/ml) and multiple bone metastases 4 years (CA19‐9: 2303 U/ml) after surgery. Increased CA19‐9 levels paralleled the clinical courses of relapse. To our knowledge, this is the first report of CA19‐9‐producing thymic NET.
Chronic dysglycemia and risk of SARS‐CoV‐2 associated respiratory failure in hospitalized patients
Authors: Rysz Susanne , Jonsson Fagerlund Malin , Rimes‐Stigare Claire , Larsson Emma , Campoccia Jalde Francesca , Mårtensson Johan
Published: September 2021

Background

Diabetes is common among patients with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐induced respiratory failure. We aimed to investigate the relationship between different stages of chronic dysglycemia and development of respiratory failure in hospitalized SARS‐CoV‐2 positive patients.

Methods

In this retrospective observational study, we included 385 hospitalized SARS‐CoV‐2 positive patients at Karolinska University Hospital, Sweden with an HbA1c test obtained within 3 months before admission. Based on HbA1c level and previous diabetes history, we classified patients into the following dysglycemia categories: prediabetes, unknown diabetes, controlled diabetes, or uncontrolled diabetes. We used multivariable logistic regression analysis adjusted for age, sex, and body mass index, to assess the association between dysglycemia categories and development of SARS‐CoV‐2‐induced respiratory failure.

Results

Of the 385 study patients, 88 (22.9%) had prediabetes, 68 (17.7%) had unknown diabetes, 36 (9.4%) had controlled diabetes, and 83 (21.6%) had uncontrolled diabetes. Overall, 299 (77.7%) patients were admitted with or developed SARS‐CoV‐2‐induced respiratory failure during hospitalization. In multivariable logistic regression analysis compared with no chronic dysglycemia, prediabetes (OR 14.41, 95% CI 5.27–39.43), unknown diabetes (OR 15.86, 95% CI 4.55–55.36), and uncontrolled diabetes (OR 17.61, 95% CI 5.77–53.74) was independently associated with increased risk of SARS‐CoV‐2‐induced respiratory failure.

Conclusion

In our cohort of hospitalized SARS‐CoV‐2 positive patients with available HbA1c data, prediabetes, undiagnosed diabetes, and poorly controlled diabetes were associated with a markedly increased risk of SARS‐CoV‐2‐associated respiratory failure.
A descriptive study of the surge response and outcomes of ICU patients with COVID‐19 during first wave in Nordic countries
Authors: Chew Michelle S. , Kattainen Salla , Haase Nicolai , Buanes Eirik A. , Kristinsdottir Linda B. , Hofsø Kristin , Laake Jon Henrik , Kvåle Reidar , Hästbacka Johanna , Reinikainen Matti , Bendel Stepani , Varpula Tero , Walther Sten , Perner Anders , Flaatten Hans K. , Sigurdsson Martin I.
Published: September 2021

Background

We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID‐19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden.

Methods

Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID‐19 disease during the first wave of COVID‐19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics.

Results

Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS‐CoV‐2, the ratio of requiring ICU admission for COVID‐19 varied substantially (1.6%–6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID‐19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%–85%) in all countries, the proportion of patients receiving renal replacement therapy (7%–26%) and various experimental therapies for COVID‐19 disease varied substantially (e.g. use of hydroxychloroquine 0%–85%). Crude ICU mortality ranged from 11% to 33%.

Conclusion

There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID‐19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.
Tools for standardized data collection: Speech, Language, and Hearing measurement protocols in the PhenX Toolkit
Authors: Morton Cynthia C. , Marazita Mary L. , Peter Beate , Rice Mabel L. , Kraft Shelly Jo , Barkmeier‐Kraemer Julie , Balaban Carey , Phillips Michael , Schoden Jennifer , Maiese Deborah , Hendershot Tabitha , Hamilton Carol M.
Published: September 2021

The PhenX Toolkit (https://www.phenxtoolkit.org/) is an online catalog of recommended measurement protocols to facilitate cross‐study analyses for biomedical research. An expert review panel (ERP) reviewed and updated the PhenX Toolkit Speech and Hearing domain to improve the precision and consistency of speech, language, and hearing disorder phenotypes. A three‐member ERP convened in August 2018 to review the measurement protocols in the PhenX Speech and Hearing domain. Aided by three additional experts in voice assessment, vertigo, and stuttering, the ERP updated the 28 protocols to reflect the latest science and technology. ERP recommendations include six new protocols, five updated protocols (from the same source), and one retired protocol. New additions include two voice‐related, three hearing‐related, and two speech‐related protocols. Additions reflect new phone/tablet applications for hearing and language, and clinical evaluations of voice. “Language” was added to the domain name, which is now “Speech, Language, and Hearing,” to represent language‐related protocols. These protocols can facilitate the assessment of speech, language, and hearing in clinical and population research. Common data elements (i.e., use of the same variables across studies) used by geneticists, otolaryngologists, audiologists, speech‐language pathologists, and in other disciplines can lead to cross‐study data integration and increased statistical power when studies are combined.