bluuebunny/crossref_metadata_2025 huggingface dataset:
A comparison of single and multi-echo processing of fMRI data during overt autobiographical recall
Authors: Gilmore Adrian W. , Agron Anna M. , González-Araya Estefanía I. , Gotts Stephen J. , Martin Alex
Published: November 2021

Recent years have seen an increase in the use of multi-echo fMRI designs by cognitive neuroscientists. Acquiring multiple echoes allows one to reduce thermal noise and identify nuisance signal components in BOLD data (Kundu et al., 2012). At the same time, multi-echo acquisitions increase data processing complexity and may incur a cost to the temporal and spatial resolution of the acquired data. Here, we re-examine a multi-echo dataset (Gilmore et al., 2021a) analyzed using multi-echo ICA (ME-ICA) and focused on hippocampal activity during the overly spoken recall of recent and remote autobiographical memories. The goal of the present series of analyses was to determine if ME-ICA’s theoretical denoising benefits might lead to a practical difference in the overall conclusions reached. Compared to single echo data, ME-ICA led to qualitatively different conclusions regarding hippocampal contributions to autobiographical recall: whereas the single echo analysis largely failed to reveal hippocampal activity relative to an active baseline, ME-ICA results supported predictions of the Standard Model of Consolidation and a time limited hippocampal involvement (Alvarez and Squire, 1994). These data provide a practical example of the benefits multi-echo denoising in a naturalistic memory paradigm and demonstrate how they can be used to address long-standing theoretical questions.
A high-fat diet changes astrocytic metabolism to enhance synaptic plasticity and promote exploratory behavior
Authors: Popov Alexander , Brazhe Nadezda , Fedotova Anna , Tiaglik Alisa , Bychkov Maxim , Morozova Kseniia , Brazhe Alexey , Aronov Dmitry , Lyukmanova Ekaterina , Lazareva Natalia , Li Li , Verkhratsky Alexei , Semyanov Alexey
Published: November 2021

A high-fat diet (HFD) is generally considered to negatively influence the body, the brain, and cognitive abilities. On the other hand, fat and fatty acids are essential for nourishing and constructing brain tissue. Astrocytes are central for lipolysis and fatty acids metabolism. Here we show that exposure of young mice to one month of HFD elevates lipid content and increases the relative amount of reduced cytochromes in astrocytes but not in neurons. Metabolic changes were paralleled with an enlargement of astrocytic territorial domains due to an increased outgrowth of branches and leaflets. Astrocyte remodeling was associated with an increase in expression of ezrin and with no changes in glial fibrillary acidic protein (GFAP), glutamate transporter-1 (GLT-1), and glutamine synthetase (GS). Such physiological (non-reactive) enlargement of astrocytes in the brain active milieu promoted glutamate clearance and long-term potentiation. These changes translated into improved exploratory behavior. Thus, dietary fat intake is not invariably harmful and might exert beneficial effects depending on the biological context.

In Brief

A high-fat diet stimulates the metabolism and growth of astrocytes, which improves glutamate clearance, synaptic plasticity, and exploratory behavior in young mice. Thus, dietary fat arguably is an essential component of the diet for children and young adults, supporting the optimal development of the brain.

Highlights

Exposure of young mice to a high-fat diet elevated lipid content and increased amount of reduced cytochromes in astrocytes but not in neurons.

Metabolic changes were paralleled with an enlargement of astrocytic territorial domains due to an increased outgrowth of branches and leaflets.

Astrocytic enlargement was associated with increased expression of ezrin but not GFAP, hence was not reactive but physiological

Expansion of astrocytes in the brain active milieu improved glutamate clearance and long-term potentiation.

The high-fat diet improved exploratory behavior in young mice.
A phosphoinositide and RAB switch controls early macropinocytosis
Authors: Spangenberg Hélène , Sneeggen Marte , Tortola Maria Mateo , Valenzuela Camila , Chang Yuen-Yan , Stenmark Harald , Raiborg Camilla , Schink Kay Oliver
Published: November 2021

Macropinocytosis is a non-selective endocytic process by which cells take up large amounts of extracellular fluids into giant vesicles known as macropinosomes. This mechanism is used by immune cells to sample the surroundings for antigens and can be exploited by cancer cells for nutrient uptake. What determines the fate of macropinosomes after they have been internalized is largely unknown. Here we investigate the role of the phosphatidylinositol 3-kinase VPS34/PIK3C3 and its product phosphatidylinositol 3-phosphate (PtdIns3P) in macropinosome fate determination. Inhibition of VPS34 led to a decrease in macropinosome survival and fluid phase uptake as well as preventing recruitment of early endosomal factors, including the small GTPase RAB5 and its effectors, to the forming macropinosomes. Instead, forming macropinosomes under VPS34 inhibition accumulated regulators of endocytic recycling, including RAB8A, RAB10, RAB11A, and PtdIns4P, which led to fusion of macropinosomes with the plasma membrane.

Whereas RAB5 was critical for macropinosome formation, macropinosome fusion with the plasma membrane depended on RAB8A. Thus, macropinosome maturation is regulated by a PtdIns3P-controlled switch that balances macropinosome fate between the default, endolysosomal maturation and an alternative, secretory route.
Cone-driven retinal responses are shaped by rod but not cone HCN1
Authors: Lankford Colten K. , Umino Yumiko , Poria Deepak , Kefalov Vladimir , Solessio Eduardo , Baker Sheila A.
Published: November 2021

Signal integration of converging neural circuits is poorly understood. One example is in the retina where the integration of rod and cone signaling is responsible for the large dynamic range of vision. The relative contribution of rods versus cones is dictated by a complex function involving background light intensity and stimulus temporal frequency. One understudied mechanism involved in coordinating rod and cone signaling onto the shared retinal circuit is the hyperpolarization activated current (Ih) mediated by HCN1 channels. Ih opposes membrane hyperpolarization driven by activation of the phototransduction cascade and modulates the strength and kinetics of the photoreceptor voltage response. We examined conditional knockout of HCN1 from rods using electroretinography. In the absence of HCN1, rod responses are prolonged in dim light which altered the response to slow modulation of light intensity both at the level of retinal signaling and behavior. Under brighter intensities, cone-driven signaling was suppressed. To our surprise, conditional knockout of HCN1 from cones had no effect on cone-mediated signaling. We propose that Ih is dispensable in cones due to the high level of temporal control of cone phototransduction. Thus, HCN1 is required for cone-driven retinal signaling only indirectly by modulating the voltage response of rods to limit their output.

GRAPHICAL ABSTRACT
Catalytic mechanism of the mitochondrial methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2)
Authors: Zhao Li Na , Kaldis Philipp
Published: November 2021

Methylenetetrahydrofolate dehydrogenase/cyclohydrolase (MTHFD2) is a new drug target that is expressed in cancer cells but not in normal adult cells, which provides an Achilles heel to selectively kill cancer cells. Despite the availability of crystal structures of MTHFD2 in the inhibitor- and cofactor-bound forms, key information is missing due to technical limitations, including (a) the location of absolutely required Mg2+ion, and (b) the substrate-bound form of MTHFD2. Using homology modeling and simulation studies, we propose that two magnesium ions are present at the active site whereby (i) Arg233, Asp225, and two water molecules coordinate MgA, while MgAtogether with Arg233 stabilize the inorganic phosphate (Pi); (ii) Asp168 and three water molecules coordinate MgB, and MgBfurther stabilizes Piby forming a hydrogen bond with two oxygens of Pi; (iii) Arg201 directly coordinates the Pi; and (iv) through three water-mediated interactions, Asp168 contributes to the positioning and stabilization of MgA, MgBand Pi. Our computational study at the empirical valence bond level allowed us to elucidate the detailed reaction mechanisms. We found that the dehydrogenase activity features a proton-coupled electron transfer with charge redistribution coupled to the reorganization of the surrounding water molecules which further facilitates the subsequent cyclohydrolase activity. The cyclohydrolase activity then drives the hydration of the imidazoline ring and the ring opening in a concerted way. Furthermore, we have uncovered that two key residues Ser197/Arg233 are key factors in determining the cofactor (NADP+/NAD+) preference of the dehydrogenase activity. Our work sheds new light on the structural and kinetic framework of MTHFD2, which will be helpful to design small molecule inhibitors that can be used for cancer therapy.
Two-speed genome expansion drives the evolution of pathogenicity in animal fungal pathogens
Authors: Wacker Theresa , Helmstetter Nicolas , Wilson Duncan , Fisher Matthew C. , Studholme David J. , Farrer Rhys A.
Published: November 2021

The origins of virulence in amphibian-infecting chytrids Batrachochytrium dendrobatidis (Bd) and Batrachochytrium salamandrivorans (Bsal) are largely unknown. Here, we use deep nanopore sequencing of Bsal and comparative genomics against 21 high-quality genome assemblies that span the fungal Chytridiomycota. Bsal has the most repeat-rich genome, comprising 40.9% repetitive elements, which has expanded to more than 3X the length of its conspecific Bd. M36 metalloprotease virulence factors are highly expanded in Bsal and 53% of the 177 unique genes are flanked by transposable elements, suggesting repeat-driven expansion. The largest M36 sub-family are mostly (84%) flanked upstream by a novel LINE element, a repeat superfamily implicated with gene copy number variations. We find that Bsal has a highly compartmentalized genome architecture, with virulence factors enriched in gene-sparse/repeat-rich compartments, while core conserved genes occur in gene-rich/repeat-poor compartments. This is a hallmark of two-speed genome evolution. Furthermore, genes with signatures of positive selection in Bd are enriched in repeat-rich regions, suggesting they are a cradle for chytrid pathogenicity evolution, and Bd also has a two-speed genome. This is the first evidence of two-speed genomes in any animal pathogen, and sheds new light on the evolution of fungal pathogens of vertebrates driving global declines and extinctions.
Autoinhibition and regulation by phosphoinositides of ATP8B1, a human lipid flippase associated with intrahepatic cholestatic disorders
Authors: Dieudonné Thibaud , Herrera Sara Abad , Laursen Michelle Juknaviciute , Lejeune Maylis , Stock Charlott , Slimani Kahina , Jaxel Christine , Lyons Joseph A. , Montigny Cédric , Pomorski Thomas Günther , Nissen Poul , Lenoir Guillaume
Published: November 2021

P4-ATPases flip lipids from the exoplasmic to the cytosolic leaflet, thus maintaining lipid asymmetry in eukaryotic cell membranes. Mutations in several human P4-ATPase genes are associated with severe diseases, e.g. in ATP8B1 causing progressive familial intrahepatic cholestasis, a rare inherited disorder progressing toward liver failure. ATP8B1 forms a binary complex with CDC50A and displays a broad specificity to glycerophospholipids, but regulatory mechanisms are unknown. Here, we report functional studies and the cryo-EM structure of the human lipid flippase ATP8B1-CDC50A at 3.1 Å resolution. We find that ATP8B1 is autoinhibited by its N- and C-terminal tails, which form extensive interactions with the catalytic sites and flexible domain interfaces. Consistently, ATP hydrolysis is unleashed by truncation of the C-terminus, but also requires phosphoinositides, most markedly phosphatidylinositol-3,4,5-phosphate (PI(3,4,5)P3), and removal of both N- and C- termini results in full activation. Restored inhibition of ATP8B1 truncation constructs with a synthetic peptide mimicking the C-terminal segment further suggests molecular communication between N- and C-termini in the autoinhibition and demonstrates that the regulatory mechanism can be interfered with by exogenous compounds. A recurring (G/A)(Y/F)AFS motif of the C-terminal segment suggests that this mechanism is employed widely across P4-ATPase lipid flippases in plasma membrane and endomembranes.
Selecting coral species for reef restoration
Authors: Madin Joshua S. , McWilliam Michael , Quigley Kate , Bay Line K. , Bellwood David , Doropoulos Christopher , Fernandes Leanne , Harrison Peter , Hoey Andrew S. , Mumby Peter J. , Ortiz Juan C. , Richards Zoe T. , Riginos Cynthia , Schiettekatte Nina , Suggett David J. , van Oppen Madeleine J. H.
Published: November 2021

Humans have long sought to restore species, but little attention has been directed at how to best select a subset of foundation species for maintaining rich assemblages that support ecosystems, like coral reefs and rainforests that are increasingly threatened by environmental change.

We propose a two-part hedging approach that selects optimized sets of species for restoration. The first part acknowledges that biodiversity supports ecosystem functions and services, and so it takes precaution against loss by ensuring an even spread of phenotypic traits. The second part maximizes species and ecosystem persistence by weighting species based on characteristics that are known to improve ecological persistence—e.g., abundance, species range and tolerance to environmental change.

Using existing phenotypic trait and ecological characteristic data for reef building corals, we identified sets of ecologically persistent species by examining marginal returns in occupancy of phenotypic trait space. We compared optimal sets of species with those from the world’s southern-most coral reef which naturally harbors low coral diversity to show these occupy much of the trait space. Comparison with an existing coral restoration program indicated that current corals used for restoration only cover part of the desired trait space and may be improved by including species with different traits.

Synthesis and applications. While there are many possible criteria for selecting species for restoration, the approach proposed here addresses the need to insure against unpredictable losses of ecosystem services by focusing on a wide range of phenotypic traits and ecological characteristics. Furthermore, the flexibility of the approach enables the functional goals of restoration to vary depending on environmental context, stakeholder values, and the spatial and temporal scales at which meaningful impacts can be achieved.
PEPc-mediated CO2assimilation provides carbons to gluconeogenesis and the TCA cycle in both dark-exposed and illuminated guard cells
Authors: Lima Valéria F. , Medeiros David B. , Cândido-Sobrinho Silvio A. , Freire Francisco Bruno S. , Porto Nicole P. , Erban Alexander , Kopka Joachim , Schwarzländer Markus , Fernie Alisdair R. , Daloso Danilo M.
Published: November 2021

Evidence suggests that guard cells have higher rate of phosphoenolpyruvate carboxylase (PEPc)-mediated dark CO2assimilation than mesophyll cells. However, it is unknown which metabolic pathways are activated following dark CO2assimilation in guard cells. Furthermore, it remains unclear how the metabolic fluxes throughout the tricarboxylic acid (TCA) cycle and associated pathways are regulated in illuminated guard cells. Here we used13C-HCO3labelling of tobacco guard cells harvested under continuous dark or during the dark-to-light transition to elucidate principles of metabolic dynamics downstream of CO2assimilation. Most metabolic changes were similar between dark-exposed and illuminated guard cells. However, illumination increased the13C-enrichment in sugars and metabolites associated to the TCA cycle. Sucrose was labelled in the dark, but light exposure increased the13C-labelling into this metabolite. Fumarate was strongly labelled under both dark and light conditions, while illumination increased the13C-enrichment in pyruvate, succinate and glutamate. Only one13C was incorporated into malate and citrate in either dark or light conditions. Our results collectively suggest that the PEPc-mediated CO2assimilation provides carbons for gluconeogenesis, the TCA cycle and glutamate synthesis and that previously stored malate and citrate are used to underpin the specific metabolic requirements of illuminated guard cells.

Highlight

PEPc-mediated CO2assimilation provides carbons for gluconeogenesis and the TCA cycle, whilst previously stored malate and citrate are used to underpin the specific metabolic requirements of illuminated guard cells.
miR-409-3p represses Cited2 at the evolutionary emergence of the callosal and corticospinal projections
Authors: Wagner Nikolaus R. , Sinha Ashis , Siththanandan Verl , Kowalchuk Angelica N. , MacDonald Jessica , Tharin Suzanne
Published: November 2021

Callosal projection neurons are a broad population of interhemispheric projection neurons that extend an axon across the corpus callosum to connect the two cerebral hemispheres. The corticospinal tract, comprised of the axons of corticospinal projection neurons, is unique to mammals, and its full extension to the lumbar segments that control walking is, like the corpus callosum, unique to placental mammals. The emergence of these two distinct axonal tracts is thought to underpin the evolutionary expansion of complex motor and cognitive abilities. The molecular mechanisms regulating the divergence of corticospinal and callosal projection neurons are incompletely understood. Our recent work identifies a genomic cluster of microRNAs (12qF1/Mirg) unique to placental mammals. These clustered miRNAs are specifically expressed by corticospinal vs. callosal projection neurons during the molecular refinement of corticospinal vs. callosal projection neuron fate (1). One of these, miR-409-3p, can convert layer V callosal into corticospinal projection neurons, acting in part through repression of the callosal-expressed transcriptional regulator Lmo4. This conversion is partial, however, suggesting that miR-409-3p represses multiple callosal projection neuron control genes in order to specify corticospinal projection neurons. One potential additional target of miR-409-3p repression is the callosal-expressed transcriptional co-activator Cited2. Cited2 interacts genetically with Lmo4, and Lmo4 can partially functionally compensate for Cited2 in thymus development(2). Further, Cited2 and Lmo4 function as opposing molecular controls over specific areal identity within superficial layer callosal projection neurons of the somatosensory and motor cortices, respectively (3). Cited2 is highly expressed by callosal, relative to corticospinal, projection neurons from the earliest stages of neurogenesis. Cited2 is necessary for the expansion of intermediate progenitor cells (IPCs) in the subventricular zone (SVZ), and the resulting generation of superficial layer callosal projection neurons. Here we show that miR-409-3p and Cited2 interact in IPCs and in corticospinal vs. deep layer callosal projection neuron development. miR-409-3p represses the Cited2 3’UTR in luciferase assays. Mirg, which encodes miR-409-3p, and Cited2, are reciprocally expressed in IPCs at e15.5 by qPCR. Furthermore, miR-409-3p gain-of-function results in a phenocopy of established Cited2 loss-of-function in IPCs. Later on, miR-409-3p and Cited2 exert opposing effects on the adoption of corticospinal vs. callosal projection neuron subtype identity. Taken together, our work suggests that miR-409-3p, and possibly other 12qF1 miRNAs, represses Cited2 in IPCs to limit their proliferation, and in developing corticospinal and deep layer callosal projection neurons to favor corticospinal fate.
Applications of AlphaFold beyond Protein Structure Prediction
Authors: Zhang Yuan , Li Peizhao , Pan Feng , Liu Hongfu , Hong Pengyu , Liu Xiuwen , Zhang Jinfeng
Published: November 2021

Predicting structures accurately for natural protein sequences by DeepMind’s AlphaFold is certainly one of the greatest breakthroughs in biology in the twenty-first century. For designed or engineered sequences, which can be unstable, predicting the stabilities together with their structures is essential since unstable structures will not function properly. We found that experimentally measured stability changes of point mutations correlate poorly with the confidence scores produced by AlphaFold. However, the stability changes can be accurately predicted using features extracted from the representations learned by AlphaFold, indicating greater generalizability of AlphaFold to designed or engineered sequences than previously thought. We then used AlphaFold to validate our previously developed protein design method, ProDCoNN, that designs sequences to fold to target protein structures given only the backbone structure information of the target proteins. We showed that ProDCoNN was able to design sequences that fold to structures very close to target structures. By combining a modified ProDCoNN, AlphaFold, and sequential Monte Carlo, we designed a novel framework to estimate the designability of protein structures. The designability of a protein structure is defined as the number of sequences, which encode the protein structure, and is an indicator of the functional robustness of proteins. For the first time, we estimated the designability of a real protein structure, chain A of FLT3 ligand (PDB ID: 1ETE) with 134 residues, as 3.12±2.14E85.
Visualization of a Standing Lattice of Scattered Light on Spherical Water Droplets under an Acoustic Field Using Biogenic Microparticles
Authors: Iwasaka Masakazu
Published: November 2021

Micromanipulation using acoustic sound is a promising technique for drug delivery, cell manipulation, biosensors, and microfluidic devices. Additionally, the visualization of acoustic fields by advanced optical measurement techniques can be combined with this micromanipulation technique. The present study reveals that a lattice pattern of reflected light appears on the surface of water droplets containing microparticles when the droplets are exposed to audible sound in the range of 1900–10000 Hz. A piezoelectric membrane providing an audible acoustic field induced a stream of microparticles on which the lattice pattern overlapped, with the appearance of a standing wave. The effects of microparticles, including BaSO4, TiO2, and guanine platelets derived from fish scales, on the formation of the lattice pattern were investigated. These three types of microparticles in water enabled a visualization of the vortex streams and generated a lattice pattern of reflected light. The guanine platelets exhibited the most precise lattice pattern over the droplet surface, with a lattice width of 100–200 μm. This phenomenon may provide a new tool for detecting and manipulating micro vortex flows in the aqueous chamber of a microfluidic device combined with an acoustic transducer.
Banp regulates DNA damage response and chromosome segregation during the cell cycle in zebrafish retina
Authors: Babu Swathy , Takeuchi Yuki , Masai Ichiro
Published: November 2021

Btg3-associated nuclear protein (Banp) was originally identified as a nuclear matrix-associated region (MAR)-binding protein and it functions as a tumor suppressor. At the molecular level, Banp regulates transcription of metabolic genes via a CGCG-containing motif called the Banp motif. However, its physiological roles in embryonic development are unknown. Here we report that Banp is indispensable for the DNA damage response and chromosome segregation during mitosis. Zebrafishbanpmutants show mitotic cell accumulation and apoptosis in developing retina. We found that DNA replication stress and tp53-dependent DNA damage responses were activated to induce apoptosis inbanpmutants, suggesting that Banp is required for regulation of DNA replication and DNA damage repair. Furthermore, consistent with mitotic cell accumulation, chromosome segregation was not smoothly processed from prometaphase to anaphase inbanpmorphants, leading to a prolonged M-phase. Our RNA- and ATAC-sequencing identified 31 candidates for direct Banp target genes that carry the Banp motif. Interestingly, a DNA replication fork regulator,wrnip1,and two chromosome segregation regulators,cenptandncapg, are included in this list. Thus, Banp directly regulates transcription ofwrnip1for recovery from DNA replication stress, andcenptandncapgfor chromosome segregation during mitosis. Our findings provide the firstin vivoevidence that Banp is required for cell-cycle progression and cell survival by regulating DNA damage responses and chromosome segregation during mitosis.
Thymic macrophages consist of two populations with distinct localization and origin
Authors: Zhou Tyng-An , Hsu Hsuan-Po , Tu Yueh-Hua , Cheng Hui-Kuei , Lin Chih-Yu , Chen Nien-Jung , Tsai Jin-Wu , Robey Ellen A. , Huang Hsuan-Cheng , Hsu Chia-Lin , Dzhagalov Ivan L.
Published: November 2021

Tissue-resident macrophages are essential to protect from pathogen invasion and maintain organ homeostasis. The ability of thymic macrophages to engulf apoptotic thymocytes is well appreciated, but little is known about their ontogeny, maintenance, and diversity. Here, we characterized the surface phenotype and transcriptional profile of these cells and defined their expression signature. Thymic macrophages were most closely related to spleen red pulp macrophages and Kupffer cells and shared the expression of the transcription factor SpiC with these cells. Single-cell RNA sequencing showed that the macrophages in the adult thymus are composed of two populations distinguished by the expression ofTimd4andCx3cr1. Remarkably,Timd4+cells were located in the cortex, whileCx3cr1+macrophages were restricted to the medulla and the cortico-medullary junction. Using shield chimeras, transplantation of embryonic thymuses, and genetic fate mapping, we found that the two populations have distinct origins.Timd4+thymic macrophages are of embryonic origin, whileCx3cr1+macrophages are derived from adult hematopoietic stem cells. Aging has a profound effect on the macrophages in the thymus.Timd4+cells underwent gradual attrition, whileCx3cr1+cells slowly accumulated with age and, in older mice, were the dominant macrophage population in the thymus. Altogether, our work defines the phenotype, origin, and diversity of thymic macrophages.
Integration of physiologically relevant photosynthetic energy flows into whole genome models of light-driven metabolism
Authors: Broddrick Jared T. , Ware Maxwell A. , Jallet Denis , Palsson Bernhard O. , Peers Graham
Published: November 2021

Characterizing photosynthetic productivity is necessary to understand the ecological contributions and biotechnology potential of plants, algae, and cyanobacteria. Light capture efficiency and photophysiology have long been characterized by measurements of chlorophyll fluorescence dynamics. However, these investigations typically do not consider the metabolic network downstream of light harvesting. In contrast, genome-scale metabolic models capture species-specific metabolic capabilities but have yet to incorporate the rapid regulation of the light harvesting apparatus. Here we combine chlorophyll fluorescence parameters defining photosynthetic and non-photosynthetic yield of absorbed light energy with a metabolic model of the pennate diatom Phaeodactylum tricornutum. This integration increases the model predictive accuracy regarding growth rate, intracellular oxygen production and consumption, and metabolic pathway usage. Additionally, our simulations recapitulate the link between mitochondrial dissipation of photosynthetically-derived electrons and the redox state of the photosynthetic electron transport chain. We use this framework to assess engineering strategies for rerouting cellular resources toward bioproducts. Overall, we present a methodology for incorporating a common, informative data type into computational models of light-driven metabolism for characterization, monitoring and engineering of photosynthetic organisms.
Intracellular development and impact of a eukaryotic parasite on its zombified microalgal host in the marine plankton
Authors: Decelle Johan , Kayal Ehsan , Bigeard Estelle , Gallet Benoit , Bougoure Jeremy , Clode Peta , Schieber Nicole , Templin Rachel , Hehenberger Elisabeth , Prensier Gerard , Chevalier Fabien , Schwab Yannick , Guillou Laure
Published: November 2021

Parasites are widespread and diverse in the oceanic plankton, and many of them infect single-celled algae for survival. How these parasites develop and scavenge energy within the host and whether the cellular organization and metabolism of the host is altered remain open questions. Combining quantitative structural and chemical imaging with time-resolved transcriptomics, we unveil dramatic morphological and metabolic changes of the parasite Amoebophrya (Syndiniales) during intracellular infection (e.g. 200-fold increase of mitochondrion volume), particularly following digestion of nutrient-rich host chromosomes. Some of these changes are also found in the apicomplexan parasites (e.g. sequential acristate and cristate mitochondrion, switch from glycolysis to TCA), thus underlining key evolutionary-conserved mechanisms. In the algal host, energy-producing organelles (chloroplast) remain intact during most of the infection, but sugar reserves diminish while lipid droplets increase. Thus, rapid infection of the host nucleus could be a zombifying strategy to digest nutrient-rich chromosomes and escape cytoplasmic defense while benefiting from the maintained C-energy production of the host cell.
System Environmental Metrics Collector for EM facilities
Authors: Alink Lambertus Michael , Eng Edward T. , Gheorghita Robert , Rice William , Cheng Anchi , Carragher Bridget , Potter Clinton S.
Published: November 2021

Recent developments in cryo-electron microscopy (cryoEM) have led to the routine determination of structures at near atomic resolution and greatly increased the number of biomedical researchers wanting access to high-end cryoEM instrumentation. The high costs and long wait times for gaining access encourages facilities to maximize instrument uptime for data collection. To support these goals, we developed a System Environmental Metrics Collector for facilities (SEMCf) that serves as a laboratory performance and management tool. SEMCf consists of an architecture of automated and robust sensors that track, organize and report key facility metrics. The individual sensors are connected to Raspberry Pi (RPi) single board computers installed in close proximity to the input metrics being measured. The system is controlled by a central server that may be installed on a RPi or existing microscope support PC. Tracking the system and the environment provides feedback of imminent issues, suggestions for interventions that are needed to optimize data production, and indications as to when preventative maintenance should be scheduled. The sensor components are relatively inexpensive and widely commercially available, and the open-source design and software enables straightforward implementation, customization, and optimization by any facility that would benefit from real time environmental monitoring and reporting.
Effect of vitamin C and E supplementation on human gastrointestinal tract tissues and cells: Raman spectroscopy and imaging studies
Authors: Miazek Krystian , Beton Karolina , Brozek-Pluska Beata
Published: November 2021

Cancer of gastrointestinal tract, such as colorectal cancer (CRC) and gastric cancer (GC), are common types of cancer globally and their origin can be linked to oxidative stress conditions. Commonly available antioxidants, such as vitamins C and E, are widely considered as potential anti-cancer agents. Raman spectra have great potential in the biochemical characterization of matter based on the fact that each molecule has its own unique vibrational properties. Raman spectroscopy allows to precisely characterized cell substructures (nucleus, mitochondria, cytoplasm, cell membrane) and components (proteins, lipids, nucleic acids).

The paper presents the application of the Raman spectroscopy technique for the analysis of tissue samples and cells of the human colon and stomach. The main goal of this study is to show the differences between healthy and cancerous tissues from the human digestive tract and human normal and cancer colon and gastric cell lines. The paper presents the spectroscopic characterization of normal colon cells - CCD-18 Co in physiological and oxidative conditions and effect of oxidative injury of normal colon cells upon supplementation with vitamin C at various concentrations based on Raman spectra. The obtained results were related to the Raman spectra recorded for human colon cancer cells - Caco-2. In addition, the effect of the antioxidant in the form of vitamin E on gastric cancer cells - HTB-135 is presented and compared with normal gastric cells - CRL-7869. All measured gastric samples were biochemically and structurally characterized by means of Raman spectroscopy and imaging. Statistically assisted analysis has shown that normal, ROS injured and cancerous human gastrointestinal cells can be distinguished based on their unique vibrational properties.

The conducted research based on Raman spectra proved that antioxidants in the form of vitamin C and E exhibit anti-cancer properties. In consequence, conducted studies proved that label-free Raman spectroscopy may play an important role in clinical diagnostics differentiation of human normal and cancerous gastrointestinal tissues and may be a source of intraoperative information supporting histopathological analysis.
Lateral entorhinal cortex suppresses drift in cortical memory representations
Authors: Pilkiw Maryna , Jarovi Justin , Takehara-Nishiuchi Kaori
Published: November 2021

Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the LEC’s activity for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the LEC’s efferent targets, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer’s disease.

SIGNIFICANCE STATEMENT

To recall past events, the brain needs to reactivate the activity patterns that occurred during those events. However, such reinstatement of memory traces is not trivial because it goes against the brain’s natural tendency to restructure the activity patterns continuously. We found that dysfunction of a brain region called the lateral entorhinal cortex (LEC) worsened the drift of the brain activity when rats repeatedly underwent the same events in the same room and made them behave as if they had never experienced these events before. Thus, the LEC stabilizes the brain activity to facilitate the recovery of the original memory trace. Failure of this process might underlie memory problems in elderly and Alzheimer’s disease patients with the degenerated LEC.
Tetramethylammonium (Z)-N′-cyanocarbamimidate
Authors: Butcher Ray J. , Purdy Andrew P.
Published: November 2021

In the structure of the tetramethyl ammonium salt of cyanourea, C4H12N+·C2H2N3O−, the N—C and O—C bond distances in the cyano and keto groups are in the normal range for such a moieties at 1.1641 (18) and 1.2550 (16) Å. However, the bonds about the central C and N atoms are much shorter than would be expected for single bonds and indicate that there is considerable electron delocalization in the anion as was also found in the silver salt. The NH2group is coplanar with the central N2CO core, in contrast with the nitrile group where the dihedral angle between the N—C—N and N2CO planes is 36.5 (3)°. The packing of the cations and anions in the unit cell involves N—H...O hydrogen bonds between anions characterized by anR22(8) motif, as well as N—H...O hydrogen bonds between anions and C—H...O interactions between both cations and anions, forming anR33(14) pattern.
Instructional leadership in sub-Saharan Africa: policy and practice
Authors: Bush Tony , Fadare Mofoluwake , Chirimambowa Tamuka , Enukorah Emmanuel , Musa Daniel , Nur Hala , Nyawo Tatenda , Shipota Maureen
Published: November 2021

Purpose

The purpose of the paper is to report the findings of a synthesis of literature reviews and stakeholder interviews conducted in Nigeria, Sierra Leone, Sudan, Tanzania, Zambia and Zimbabwe. The synthesis provides an overview of instructional leadership policy and practice in these six countries.

Design/methodology/approach

This paper reports the findings of a systematic literature review, and participant interviews, in six sub-Sahara African countries. The research links to the British Council's initiative to develop instructional leadership in developing contexts, including the six countries featured in this submission.

Findings

The findings show diverse policy and practice of instructional leadership in these African contexts. Three have no explicit policies on this important leadership construct, while the others have relevant policy statements but limited evidence of instructional leadership practice.

Research limitations/implications

The research provides an overview of instructional leadership policy and practice in these six countries, but more school-based research is required to develop grounded evidence on whether and how this is practiced. The pandemic inhibited such school-based research in 2020. The study provides emerging evidence of the impact of instructional leadership on school and student outcomes, confirming what is known from international research.

Practical implications

Developing awareness of how instructional leadership can improve student learning, linked to appropriate training, could lead to more effective schools.

Social implications

The Sustainable Development Goals stress the importance of high quality education for economic and social development. Leadership is an important aspect of quality, and the research reported in this paper shows the potential for instructional leadership to enhance student learning.

Originality/value

This is the first cross-national study of instructional leadership in sub-Saharan Africa.
Service outsourcing contract design under asymmetric information
Authors: Xia Yu , Xie Jiqing , Zhang Guangsi , Zhu Weijun
Published: November 2021

Purpose

Upstream suppliers attempt to outsource product after-sales services to midstream third-party service providers while selling the product directly to downstream sellers, forming a networked supply chain. However, a problem of information asymmetry in the market demand among supply chain members exists. The authors investigate the impact of demand information asymmetry among third-party service providers, upstream suppliers and downstream sellers in the supply chain on the supplier's contract selection under the networked framework.

Design/methodology/approach

The authors establish a model in which the supplier can use a wholesale price contract and facilitate a signaling game between the third-party service provider and the seller. Conversely, the supplier could use a menu contract to establish an incentive mechanism to solve information asymmetry. The authors propose heuristic algorithms to quickly estimate a supplier's optimal profit.

Findings

The results show that when the demand forecasting bias is relatively small, the use of a menu contract by the supplier could eliminate information asymmetry; when the demand forecasting bias is large enough, the signaling mechanism between the third-party service provider and the seller could alleviate the double marginalization effect in the supply chain. Although it is common to solve the asymmetric information problem by establishing incentive mechanisms, the authors found that in the latter case, the supplier is better off when no incentive mechanisms are implemented in the networked supply chain.

Originality/value

This study compares screening and signaling effects and compares firms' profits in both cases.
COVID‐19 and vertical transmission: assessing the expression of ACE2/TMPRSS2 in the human fetus and placenta to assess the risk of SARS‐CoV‐2 infection
Authors: Beesley MA , Davidson JR , Panariello F , Shibuya S , Scaglioni D , Jones BC , Maksym K , Ogunbiyi O , Sebire NJ , Cacchiarelli D , David AL , De Coppi P , Gerli MFM
Published: November 2021

Background

Pregnant women have been identified as a potentially at‐risk group concerning COVID‐19 infection, but little is known regarding the susceptibility of the fetus to infection. Co‐expression of ACE2 and TMPRSS2 has been identified as a prerequisite for infection, and expression across different tissues is known to vary between children and adults. However, the expression of these proteins in the fetus is unknown.

Methods

We performed a retrospective analysis of a single cell data repository. The data were then validated at both gene and protein level by performing RT‐qPCR and two‐colour immunohistochemistry on a library of second‐trimester human fetal tissues.

Findings

TMPRSS2 is present at both gene and protein level in the predominantly epithelial fetal tissues analysed. ACE2 is present at significant levels only in the fetal intestine and kidney, and is not expressed in the fetal lung. The placenta also does not co‐express the two proteins across the second trimester or at term.

Interpretation

This dataset indicates that the lungs are unlikely to be a viable route of SARS‐CoV2 fetal infection. The fetal kidney, despite presenting both the proteins required for the infection, is anatomically protected from the exposure to the virus. However, the gastrointestinal tract is likely to be susceptible to infection due to its high co‐expression of both proteins, as well as its exposure to potentially infected amniotic fluid.

Tweetable abstract

This work provides detailed mechanistic insight into the relative protection & vulnerabilities of the fetus & placenta to SARS‐CoV‐2 infection by scRNAseq & protein expression analysis for ACE2 & TMPRSS2. The findings help to explain the low rate of vertical transmission.
Predicting the recurrence of chronic rhinosinusitis with nasal polyps using nasal microbiota
Authors: Zhao Yan , Chen Junru , Hao Yun , Wang Boqian , Wang Yue , Liu Qinghua , Zhao Jinming , Li Ying , Wang Ping , Wang Xiangdong , Zhang Peng , Zhang Luo
Published: November 2021

Background

Recent studies have revealed that the nasal microbiota in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) is profoundly altered and is correlated with systemic inflammation. However, little is known regarding whether the microbiota can be utilized to predict nasal polyp recurrence. This study is aimed to determine whether altered nasal microbiota constituents could be used as biomarkers to predict CRSwNP recurrence.

Methods

Nasal microbiota constituents were quantified and characterized using bacterial 16S ribosomal RNA gene sequencing. Selected features for least absolute shrinkage and selection operator regression‐based predictors were the nasal microbiota community composition and CRSwNP patient clinical characteristics. The primary outcome was recurrence, which was determined post‐admission.

Results

By distinguishing recurrence‐associated nasal microbiota taxa and exploiting the distinct nasal microbiota abundance between patients with recurrent and non‐recurrent CRSwNP, we developed a predictive classifier for the diagnosis of nasal polyps' recurrence with 91.4% accuracy.

Conclusions

Key taxonomical features of the nasal microbiome could predict recurrence in CRSwNP patients. The nasal microbiome is an understudied source of clinical variation in CRSwNP and represents a novel therapeutic target for future prevention and treatment.
Accelerating adaptation in the adaptive Metropolis–Hastings random walk algorithm
Authors: Spencer Simon E.F.
Published: November 2021

The Metropolis–Hastings random walk algorithm remains popular with practitioners due to the wide variety of situations in which it can be successfully applied and the extreme ease with which it can be implemented. Adaptive versions of the algorithm use information from the early iterations of the Markov chain to improve the efficiency of the proposal. The aim of this paper is to reduce the number of iterations needed to adapt the proposal to the target, which is particularly important when the likelihood is time‐consuming to evaluate. First, the accelerated shaping algorithm is a generalisation of both the adaptive proposal and adaptive Metropolis algorithms. It is designed to remove, from the estimate of the covariance matrix of the target, misleading information from the start of the chain. Second, the accelerated scaling algorithm rapidly changes the scale of the proposal to achieve a target acceptance rate. The usefulness of these approaches is illustrated with a range of examples.
Factors influencing aspirations for practice ownership by veterinary professional students at the University of Sydney
Authors: Thompson B , Allan F
Published: November 2021

Understanding the factors that influence the aspirations of future veterinary practitioners is critical to assist succession planning. The aim of this study was to discover factors that currently influence veterinary students' desire to own a veterinary practice in the future, including whether these aspirations were influenced by a student's experience throughout their years of veterinary studies. The study surveyed University of Sydney students enrolled in the postgraduate Doctor of Veterinary Medicine (DVM) degree in 2020. A response rate of 29% was obtained (142/508). Of those 142 respondents, 50 (35%) indicated that they wished to own a practice in the future, 40 (28%) indicated that they did not wish to own a practice in the future and 52 (37%) were unsure. The results demonstrate that practice ownership is currently only influenced by factors that are external to a student's experience at university, given that there was no significant difference between practice ownership aspirations between DVM years. After excluding those who were unsure, veterinary students whose parents or guardians own, or have owned, a business are three times more likely (OR = 3.19; 95% CI = 1.35–7.73; P < 0.01) to aspire to practice ownership than those students whose parents have not. Asian students showed significantly less interest in practice ownership than Caucasian students (OR = 0.41; 95% CI = 0.16–0.99, P < 0.05). Further qualitative research is required to better understand these findings so that tailored advice can be provided to students and veterinary schools to positively support graduating veterinary professionals towards future practice ownership.