bluuebunny/crossref_metadata_2025 huggingface dataset:
Abundance and Microbial Diversity from Surface to Deep Water Layers Over the Rio Grande Rise, South Atlantic
Authors: Ferreira Juliana Correa Neiva , Bergo Natascha M. , Tura Pedro M. , Chuqui Mateus Gustavo , Brandini Frederico P. , Jovane Luigi , Pellizari Vivian H.
Published: April 2021

Marine microbes control the flux of matter and energy essential for life in the oceans. Until now, the distribution and diversity of planktonic microorganisms above Fe-Mn crusts has received relatively little attention. Future mining\dredging of these minerals is predicted to affect microbial diversity and functioning in the deep sea. Here, we studied the ecology of planktonic microbes among pelagic environments of an Fe-Mn deposit region, at Rio Grande Rise, Southwestern Atlantic Ocean. We investigated microbial community composition using high-throughput sequencing of 16S rRNA genes and their abundance estimated by flow cytometry. Our results showed that the majority of picoplanktonic was found in epi- and mesopelagic waters, corresponding to the Tropical Water and South Atlantic Central Water. Bacterial and archaeal groups related to phototrophy, heterotrophy and chemosynthesis, such asSynechococcales, Sar11 (Proteobacteria) and Nitrosopumilales (Thaumarchaeota) were the main representatives of the pelagic microbial community. Additionally, we detected abundant assemblages involved in biodegradation of marine organic matter and iron oxidation at deep waters, i.e.,PseudoalteromonasandAlteromonas. No differences were observed in microbial community alpha diversity. However, we detected differences in community structure between water masses, suggesting that changes in an environmental setting (i.e. nutrient availability or circulation) play a significant role in structuring the pelagic zones, also affecting the meso- and bathypelagic microbiome.

Highlights

Rio Grande Rise pelagic microbiome

Picoplankton carbon biomass partitioning through pelagic zones

Unique SAR11 Clade I oligotype in the shallowest Tropical Water

Higher number of shared oligotypes between deepest water masses

Nitrogen, carbon and sulfur may be important contributors for the pelagic microbiome
MG53 slows neuromuscular junction loss and prolongs survival in ALS
Authors: Yi Jianxun , Li Ang , Li Xuejun , Park Ki Ho , Zhou Xinyu , Yi Frank , Xiao Yajuan , Yoon Dosuk , Tan Tao , Ostrow Lyle W. , Ma Jianjie , Zhou Jingsong
Published: April 2021

Respiratory failure from progressive respiratory muscle weakness is the most common cause of death in amyotrophic lateral sclerosis (ALS). Defects in neuromuscular junctions (NMJs) and progressive NMJ loss occur at early stages, thus stabilizing and preserving NMJs represents a potential therapeutic strategy to slow ALS disease progression. Here we demonstrate that NMJ damage is repaired by MG53, an intrinsic muscle protein involved in plasma membrane repair. Compromised diaphragm muscle membrane repair and NMJ integrity are early pathological findings in ALS. Diaphragm muscles from ALS mouse models show increased susceptibility to injury and intracellular MG53 aggregation, which is also a hallmark of human muscle samples from ALS patients. We show that systemic administration of recombinant human MG53 protein (rhMG53) in ALS mice protects against injury to diaphragm muscle, preserves NMJ integrity, and slows ALS disease progression. As MG53 is present in circulation in rodents and humans under physiological conditions, our findings provide proof-of-concept data supporting MG53 as a potentially safe and effective therapy to mitigate ALS progression.
Fine carbohydrate structure governs the structure and function of human gut microbiota independently of variation in glycosyl residue composition
Authors: Marcia Arianna D. Romero , Yao Tianming , Chen Ming-Hsu , Oles Renee E. , Lindemann Stephen R.
Published: April 2021

Increased dietary fiber consumption has been shown to increase human gut microbial diversity, but the mechanisms driving this effect remain unclear. One possible explanation is that microbes are able to divide metabolic labor in consumption of complex carbohydrates, which are composed of diverse glycosidic linkages that require specific cognate enzymes for degradation. However, as naturally derived fibers vary in both sugar composition and linkage structure, it is challenging to separate out the impact of each of these variables. We hypothesized that fine differences in carbohydrate linkage structure would govern microbial community structure and function independently of variation in glycosyl residue composition. To test this hypothesis, we fermented commercially available soluble resistant glucans, which are uniformly composed of glucose linked in different structural arrangements,in vitrowith fecal inocula from each of three individuals. We measured metabolic outputs (pH, gas, and short-chain fatty acid production) and community structure via 16S rRNA amplicon sequencing. We determined that community metabolic outputs from identical glucans were highly individual, emerging from divergent initial microbiome structures. However, specific operational taxonomic units responded similarly in growth responses across individuals’ microbiota, though in context-dependent ways; these data suggested that certain taxa were more efficient in competing for some structures than others. Together, these data support the hypothesis that variation in linkage structure, independent of sugar composition, governs compositional and functional responses of microbiota.

Importance

Previous studies have reported how physical and chemical structures of carbohydrates influence the gut microbiota, however, variability across dietary fibers in monosaccharide composition and linkage structure obscures the relationship between fine polysaccharide linkage structure and microbial fitness. Revealing connections between subtle differences in glucan structure and microbial composition and metabolic responses, this study suggests much greater attention to substrate structure in the design of experiments to test fiber-microbiome responsesin vitroandin vivo. Further, it underscores that, although microbiome responses to distinct fibers are individual and vary among specific glucans, similar carbohydrate structure-microbe relationships occur across individual donor communities. Together, these data may help explain why some individuals may respond (while others do not) to fiber treatments in human feeding trials and support the long-term goal of rational inclusion of specific fibers in dietary patterns to modulate the gut microbiome in support of health.
Torsions-Driven Root Helical Growth, Waving And Skewing InArabidopsis
Authors: Zhou Ke
Published: April 2021

Helical growth broadly exists in immobile plants to support their limited movement, andArabidopsisseedling root exhibiting natural left-handedness helical growth is considered as a simplified model for investigating this interesting behavior. Efforts have been made for understanding the mechanism of root helical growth and consequent root waving and skewing on tilted and impenetrable surface, and several models have been established. Here, previous reports are reviewed and a straightforward torsions-driven mechanism has been emphasized, and additional experiments have been performed to fill up the gaps of this theory in our study.

This study implies that, torsions originating from handedness of both cortical microtubules and cellulose microfibrils play central role in root handed helical growth. Different from torsions directly provided by handed assembled cortical microtubules, torsions originating from right-handed assembled cellulose microfibrils are relaxed by their cross-linking with pectin within cell wall, but only exhibited when their cross-linking is interrupted due to damaged cell wall integrity. To topologically relax these torsions, supercoils of cortical microtubules and/or cellulose microfibrils exhibiting as oblique alignments are formed in root cells, which alter the orientation of root cell files and generate handed helical roots. Working together with gravitropic response, relaxation of torsions originating from helical roots drives roots to elongate with handedness, which therefore produces waved and skewed roots on tilted and impenetrable surface.
Augmentation of CD47-SIRPα signaling protects cones in genetic models of retinal degeneration
Authors: Wang Sean K. , Xue Yunlu , Cepko Constance L.
Published: April 2021

Inherited retinal diseases such as retinitis pigmentosa (RP) can be caused by thousands of different mutations, a small number of which have been successfully treated with gene replacement. However, this approach has yet to scale and may be infeasible in many cases, highlighting the need for interventions that could benefit more patients. Here, we found that microglial phagocytosis is upregulated during cone degeneration in RP, suggesting that expression of “don’t eat me” signals such as CD47 might confer protection to cones. To test this, we delivered an adeno-associated viral (AAV) vector expressing CD47 on cones, which promoted cone survival in three mouse models of RP and preserved visual function. Cone rescue with CD47 required signal regulatory protein alpha (SIRPα) but not microglia or thrombospondin-1 (TSP1), suggesting that CD47 interacts with SIRPα on non-microglial cells to alleviate degeneration. These findings establish augmentation of CD47-SIRPα signaling as a potential treatment strategy for RP and possibly other forms of neurodegeneration.
Altered synaptic connectivity and brain function in mice lacking microglial adapter protein Iba1
Authors: Lituma Pablo J. , Woo Evan , O’Hara Bruce F. , Castillo Pablo E. , Sibinga Nicholas E. S. , Nandi Sayan
Published: April 2021

Growing evidence indicates that microglia impact brain function by regulating synaptic pruning and formation, as well as synaptic transmission and plasticity. Iba1 (Ionized Ca+2-binding adapter protein 1), encoded by theAllograft inflammatory factor 1(Aif1) gene, is an actin-interacting protein in microglia. Although Iba1 has long been used as a cellular marker for microglia, its functional role remains unknown. Here, we used global Iba1-deficient (Aif1-/-) mice to characterize microglial activity, synaptic function and behavior. Microglial imaging in acute hippocampal slices and fixed tissues from juvenile mice revealed thatAif1-/-microglia display reductions in ATP-induced motility and ramification, respectively. Biochemical assays further demonstrated thatAif1-/-brain tissues exhibit an altered expression of microglial-enriched proteins associated with synaptic pruning. Consistent with these changes, juvenileAif1-/-mice displayed deficits in excitatory synapse number and synaptic transmission assessed by neuronal labeling and whole-cell patch-clamp recording in acute hippocampal slices. Unexpectedly, microglial synaptic engulfment capacity was diminished in juvenileAif1-/-mice. During early postnatal development when synapse formation is a predominant event in the hippocampus, excitatory synapse number was still reduced inAif1-/-mice. Together these findings support an overall role of Iba1 in excitatory synaptic growth in juvenile mice. Lastly, postnatal synaptic deficits persisted in the adulthood and correlated with significant behavioral changes in adultAif1-/-mice, which exhibited impairments in object recognition memory and social interaction. These results suggest that Iba1 critically contributes to microglial activity underlying essential neuro-glia developmental processes that may deeply influence behavior.

Significance

Abnormal microglia-neuron interaction is increasingly implicated in neurodevelopmental and neuropsychiatric conditions such as autism spectrum disorders and schizophrenia, as well as in neurodegenerative disorders such as Alzheimer’s disease. This study demonstrates that deletion of the microglia-specific protein Iba1, which has long been utilized as a selective microglial marker but whose role has remained unidentified, results in microglial structural and functional impairments that significantly impact synaptic development and behavior. These findings not only highlight the importance of microglia in brain function but may also suggest that modifying microglial function could provide a therapeutic strategy for treatment of neurodevelopmental, neuropsychiatric and neurodegenerative disorders.
MSH2-MSH3 promotes DNA end resection during HR and blocks TMEJ through interaction with SMARCAD1 and EXO1
Authors: Oh Jung-Min , Kang Yujin , Park Jumi , Sung Yubin , Kim Dayoung , Seo Yuri , Lee Eun A , Ra Jae Sun , Amarsanaa Enkhzul , Park Young-Un , Kim Hongtae , Schärer Orlando , Cho Seung Woo , Lee Changwook , Takata Kei-ichi , Lee Ja Yil , Myung Kyungjae
Published: April 2021

DNA double strand break (DSB) repair by Homologous recombination (HR) is initiated by the end resection, a process during which 3’ ssDNA overhangs are generated by the nucleolytic degradation. The extent of DNA end resection determines the choice of the DSB repair pathway. The role of several proteins including nucleases for end resection has been studied in detail. However, it is still unclear how the initial, nicked DNA generated by MRE11-RAD50-NBS1 is recognized and how subsequent proteins including EXO1 are recruited to DSB sites to facilitate extensive end resection. We found that the MutSβ (MSH2-MSH3) mismatch repair (MMR) complex is recruited to DSB sites by recognizing the initial nicked DNA at DSB sites through the interaction with the chromatin remodeling protein SMARCAD1. MSH2-MSH3 at DSB sites helps to recruit EXO1 for long-range resection and enhances its enzymatic activity. MSH2-MSH3 furthermore inhibits the access of DNA polymerase θ (POLQ), which promotes polymerase theta-mediated end-joining (TMEJ) of DSB. Collectively, our data show a direct role for MSH2-MSH3 in the initial stages of DSB repair by promoting end resection and influencing DSB repair pathway by favoring HR over TMEJ. Our findings extend the importance of MMR in DSB repair beyond established role in rejecting the invasion of sequences not perfectly homologous to template DNA during late-stage HR.
Identification of the three zinc-binding sites on Tau protein
Authors: La Rocca Romain , Tsvetkov Philipp O. , Golovin Andrey V. , Allegro Diane , Barbier Pascale , Malesinski Soazig , Guerlesquin Françoise , Devred François
Published: April 2021

Tau protein has been extensively studied due to its key roles in microtubular cytoskeleton regulation and in the formation of aggregates found in some neurodegenerative diseases. Recently it has been shown that zinc is able to induce tau aggregation by interacting with several binding sites. However, the precise location of these sites and the molecular mechanism of zinc-induced aggregation remain unknown. Here we used Nuclear Magnetic Resonance (NMR) to identify zinc binding sites on hTau40 isoform. These experiments revealed three distinct zinc binding sites on tau, located in the N-terminal part (H14, H32, H94, and H121), the repeat region (H299, C322, H329 and H330) and the C-terminal part (H362, H374, H388 and H407). Further analysis enabled us to show that the C-terminal and the N-terminal sites are independent of each other. Using molecular simulations, we modeled the structure of each site in a complex with zinc. Given the clinical importance of zinc in tau aggregation, our findings pave the way for designing potential therapies for tauopathies.

Highlights

Zinc is known to induce tau aggregation in neurodegenerative diseases

Zinc binding locations and mechanism are not yet clear

Using NMR we localized 3 zinc binding site on tau

By molecular simulations, we proposed a modeled structure of each site

Our findings pave the way for designing potential therapies for tauopathies
Endomembranes promote chromosome missegregation by ensheathing misaligned chromosomes
Authors: Ferrandiz Nuria , Downie Laura , Starling Georgina P. , Royle Stephen J.
Published: April 2021

Errors in mitosis that cause chromosome missegregation lead to aneuploidy and micronuclei formation which are associated with cancer. Accurate segregation requires the alignment of all chromosomes by the mitotic spindle at the metaphase plate, and any misalignment must be corrected before anaphase is triggered. The spindle is situated in a membrane-free “exclusion zone”, beyond this zone, endomembranes (endoplasmic reticulum, nuclear envelope and other organelles) are densely packed. We asked what happens to misaligned chromosomes that find themselves beyond the exclusion zone? Here we show that such chromosomes become ensheathed in multiple layers of endomembranes. Chromosome ensheathing delays mitosis and increases the frequency of chromosome missegregation. The micronuclei that form following missegregation have a disrupted nuclear envelope with internal endomembranes. We use an induced organelle relocalization strategy in live cells to show that clearance of endomembranes allows for the rescue of chromosomes that were destined for missegregation. Our findings indicate that endomembranes promote the missegregation of misaligned chromosomes that are outside the exclusion zone, and therefore constitute a risk factor for aneuploidy.
Dopamine desynchronizes the retinal clock through a melanopsin-dependent regulation of acetylcholine retinal waves during development
Authors: Kinane Chaimaa , Calligaro Hugo , Jandot Antonin , Coutanson Christine , Haddjeri Nasser , Bennis Mohamed , Dkhissi-Benyahya Ouria
Published: April 2021

Dopamine (DA) plays a critical role in retinal physiology, including resetting of the retinal circadian clock that in turn regulates DA release. DA acts on major classes of retinal cells by reconfiguring electrical and chemical synapses. Although a bidirectional regulation between intrinsically photosensitive melanopsin ganglion cells (ipRGCs) and dopaminergic cells has been demonstrated during development and adulthood, DA involvement in the ontogeny of the retinal clock is still unknown.

Using wild-typePer2Lucand melanopsin knockout (Opn4-/-::Per2Luc) mice at different postnatal stages, we found that the retina can generate self-sustained circadian rhythms from postnatal day 5 that emerge in the absence of external time cues in both genotypes. Intriguingly, DA lengthens the endogenous period only in wild-type retinas, suggesting that this desynchronizing effect requires melanopsin. Furthermore, blockade of cholinergic retinal waves in wild-type retinas induces a shortening of the period, similarly toOpn4-/-::Per2Lucexplants. Altogether, these data suggest that DA desynchronizes the retinal clock through a melanopsin-dependent regulation of acetylcholine retinal waves, thus offering a new role of melanopsin in setting the period of the retinal clock during development.
Versioning Biological Cells for Trustworthy Cell Engineering
Authors: Tellechea-Luzardo Jonathan , Hobbs Leanne , Velázquez Elena , Pelechova Lenka , Woods Simon , de Lorenzo Victor , Krasnogor Natalio
Published: April 2021

“Full-stack”biotechnology platforms for cell line (re)programming are on the horizon, due mostly to (a) advances in gene synthesis and editing techniques as well as (b) the growing integration with informatics, the internet of things and automation. These emerging platforms will accelerate the production and consumption of biological products. Hence, transparency, traceability and -ultimately-trustworthiness is required -from cradle to grave- for engineered cell lines and their engineering processes. We report here the first version control system for cell engineering that integrates a new cloud-based version control software for cell lines’ digital footprint with molecular barcoding of living samples. We argue that version control for cell engineering marks a significant step towards more open, reproducible, easier to trace and share, and more trustworthy engineering biology.

One Sentence Summary

We demonstrate a transparent and open way of engineering and sharing cell lines.
GFAT2 and AMDHD2 act in tandem to control the hexosamine biosynthetic pathway
Authors: Kroef Virginia , Ruegenberg Sabine , Horn Moritz , Allmeroth Kira , Ebert Lena , Bozkus Seyma , Miethe Stephan , Schermer Bernhard , Baumann Ulrich , Denzel Martin S.
Published: April 2021

The hexosamine biosynthetic pathway (HBP) produces the essential metabolite UDP-GlcNAc and plays a key role in metabolism, cancer, and aging. The HBP is controlled by its rate-limiting enzyme glutamine fructose-6-phosphate amidotransferase (GFAT) that is directly inhibited by UDP-GlcNAc in a feedback loop. HBP regulation by GFAT is well studied but other HBP regulators have remained obscure. Elevated UDP-GlcNAc levels counteract the glycosylation toxin tunicamycin (TM) and thus we screened for TM resistance in haploid mouse embryonic stem cells (mESCs) using random chemical mutagenesis to pinpoint new HBP regulators. We identified the N-acetylglucosamine deacetylase AMDHD2 that catalyzes a reverse reaction in the HBP and its loss strongly elevated UDP-GlcNAc. To better understand AMDHD2, we solved the crystal structure and found that loss-of-function is caused by protein destabilization or interference with its catalytic activity. Finally, we show that mESCs express AMDHD2 together with GFAT2 instead of the more common paralog GFAT1. Compared with GFAT1, GFAT2 had a much lower sensitivity to UDP-GlcNAc inhibition, explaining how AMDHD2 loss-of-function resulted in HBP activation. This HBP configuration in which AMDHD2 serves to balance GFAT2 activity was also observed in other mESCs and, consistently, the GFAT2/GFAT1 ratio decreased with differentiation of mouse and human embryonic stem cells. Together, our data reveal a critical function of AMDHD2 in limiting UDP-GlcNAc production in cells that use GFAT2 for metabolite entry into the HBP.
Social foraging in vampire bats is predicted by long-term cooperative relationships
Authors: Ripperger Simon P. , Carter Gerald G.
Published: April 2021

Stable social bonds in group-living animals can provide greater access to food. A striking example is that female vampire bats often regurgitate blood to socially bonded kin and nonkin that failed in their nightly hunt. Food-sharing relationships form via preferred associations and social grooming within roosts. However, it remains unclear whether these cooperative relationships extend beyond the roost. To evaluate if long-term cooperative relationships in vampire bats play a role in foraging, we tested if foraging encounters measured by proximity sensors could be explained by wild roosting proximity, kinship, or rates of co-feeding, social grooming, and food sharing during 22 months in captivity. We assessed evidence for six hypothetical scenarios of social foraging, ranging from individual to collective hunting. We found that female vampire bats departed their roost individually, but often re-united far outside the roost. Nonrandomly repeating foraging encounters were predicted by within-roost association and histories of cooperation in captivity, even when controlling for kinship. Foraging bats demonstrated both affiliative and competitive interactions and a previously undescribed call type. We suggest that social foraging could have implications for social evolution if ‘local’ cooperation within the roost and ‘global’ competition outside the roost enhances fitness interdependence between frequent roostmates.
Restriction ofWolbachiabacteria in early embryogenesis of neotropicalDrosophilaspecies via ER-mediated autophagy
Authors: Strunov Anton , Schmidt Katy , Kapun Martin , Miller Wolfgang J.
Published: April 2021

Wolbachiabacteria are maternally transmitted intracellular microbes that are not only restricted to the reproductive organs but also found in various somatic tissues of their native hosts. The abundance of the endosymbiont in somatic tissues, usually a dead end for vertically transmitted bacteria, causes a multitude of effects on life history traits of their hosts, which are still not well understood. Thus, deciphering the host-symbiont interactions on a cellular level throughout a host’s lifecycle is of great importance to understand their homeostatic nature, persistence and spreading success. Using fluorescent and transmission electron microscopy, we conducted a comprehensive analysis ofWolbachiatropism in somatic and reproductive tissues of sixDrosophilaspecies at the intracellular level during host development. Our data uncovered diagnostic patterns of infections to embryonic primordial germ cells and to particular cells of somatic tissues in three different neotropicalDrosophilaspecies of the willistoni and saltans groups that have apparently evolved in both independently. We further found that restricted patterns ofWolbachiatropism are already determined in early fly embryogenesis. This is achieved via selective autophagy, and the restriction of infection is preserved through larval hatching and metamorphosis. We further uncovered tight interactions ofWolbachiawith membranes of the endoplasmic reticulum, which might play a scaffolding role for autophagosome formation and subsequent elimination of the endosymbiont. Finally, by analyzingD. simulanslines transinfected with non-nativeWolbachia, we uncovered that the host genetic background regulates tissue tropism of infection. Our data demonstrate a peculiar and novel mechanism to limit and spatially restrict bacterial infection in somatic tissues during a very early stage of host development.
A key role of astrocytic calcium dynamics to link neuronal activity with the BOLD signal
Authors: Tesler Federico , Linne Marja-Leena , Destexhe Alain
Published: April 2021

Functional magnetic resonance imaging (fMRI) relies on the coupling between neuronal and vascular activity, but the mechanisms behind this coupling are still under discussion. Recent experimental evidence suggests that calcium signaling may play a significant role in neurovascular coupling. However, it is still controversial where this calcium signal is located (in neurons or elsewhere), how it operates and how relevant is its role. In this paper we introduce a biologically plausible model of the neurovascular coupling and we show that calcium signaling in astrocytes can explain the main aspects of the dynamics of the coupling. We find that calcium signaling can explain so-far unrelated features such as the linear and non-linear regimes, the negative vascular response (undershoot) and the emergence of a (calcium-driven) Hemodynamic Response Function. These features are reproduced here for the first time by a single model of the detailed neuronal-astrocyte-vascular pathway. Furthermore, we analyze how information is coded and transmitted from the neuronal to the vascular system and we find that frequency modulation of astrocytic calcium dynamics plays a key role in this process. Finally, our work provides a framework to link neuronal activity to the BOLD signal, and vice-versa, where neuronal activity can be inferred from the BOLD signal. This opens new ways to link known alterations of astrocytic calcium signaling in neurodegenerative diseases (e.g. Alzheimer’s and Parkinson’s diseases) with detectable changes in neurovascular coupling.
Large-scale analysis of SARS-CoV-2 synonymous mutations reveals the adaptation to the human codon usage during the virus evolution
Authors: Ramazzotti Daniele , Angaroni Fabrizio , Maspero Davide , Mauri Mario , D’Aliberti Deborah , Fontana Diletta , Antoniotti Marco , Elli Elena Maria , Graudenzi Alex , Piazza Rocco
Published: April 2021

Many large national and transnational studies have been dedicated to the analysis of SARS-CoV-2 genome, most of which focused on missense and nonsense mutations. However, approximately 30% of the SARS-CoV-2 variants are synonymous, therefore changing the target codon without affecting the corresponding protein sequence.

By performing a large-scale analysis of sequencing data generated from almost 400,000 SARS-CoV-2 samples, we show that silent mutations increasing the similarity of viral codons to the human ones tend to fixate in the viral genome over-time. This indicates that SARS-CoV-2 codon usage is adapting to the human host, likely improving its effectiveness in using the human aminoacyl-tRNA set through the accumulation of deceitfully neutral silent mutations.

One-Sentence Summary

Synonymous SARS-CoV-2 mutations related to the activity of different mutational processes may positively impact viral evolution by increasing its adaptation to human codon usage.
Spatiotemporal cytokinin signaling imaging reveals IPT3 function in nodule development inMedicago truncatula
Authors: Triozzi Paolo M. , Irving Thomas B. , Schmidt Henry W. , Keyser Zachary P. , Chakraborty Sanhita , Balmant Kelly M. , Pereira Wendell J. , Dervinis Christopher , Mysore Kirankumar S. , Wen Jiangqi , Ané Jean-Michel , Kirst Matias , Conde Daniel
Published: April 2021

Most legumes can establish a symbiotic association with soil rhizobia that triggers the development of root nodules. These nodules host the rhizobia and allow them to fix nitrogen efficiently. The perception of bacterial lipo-chitooligosaccharide (LCO) signal in the epidermis initiates a signaling cascade that allows rhizobial intracellular infection in the root and de-differentiation and activation of cell division that gives rise to the nodule. Nodule organogenesis and rhizobial infection need to be coupled in space and time for successful nodulation. The plant hormone cytokinin (CK) acts as an essential positive regulator of nodule organogenesis, and specific CK receptors are required for nodule formation. Temporal regulation of tissue-specific CK signaling and biosynthesis in response to LCOs orSinorhizobium melilotiinoculation inMedicago truncatularemains poorly understood. In the present study, using a fluorescence-based CK sensor (TCSn::nls:tGFP), we performed a high-resolution tissue-specific temporal characterization of the CK response’s sequential activation during root infection and nodule development inM. truncatulaafter inoculation withS. meliloti. Loss-of-function mutants of the CK-biosynthetic geneISOPENTENYL TRANSFERASE 3(IPT3) showed impairment of nodulation, suggesting that IPT3 is required for nodule development inM. truncatula. Simultaneous live imaging ofpIPT3::tdTOMATOand the CK sensor showed thatIPT3induction in the root stele at the base of nodule primordium contributes to CK biosynthesis, which in turn promotes expression of positive regulators of nodule organogenesis inM. truncatula.

One-sentence summary

High-resolution spatiotemporal imaging of cytokinin signaling reveals IPT3 function during indeterminate nodule development inMedicago truncatula
TheBrachypodium distachyoncold-acclimated plasma membrane proteome is primed for stress resistance
Authors: Juurakko Collin L. , Bredow Melissa , Nakayama Takato , Imai Hiroyuki , Kawamura Yukio , diCenzo George C. , Uemura Matsuo , Walker Virginia K.
Published: April 2021

In order to survive sub-zero temperatures, some plants undergo cold acclimation where low, non-freezing temperatures and/or shortened day lengths allow cold hardening and survival during subsequent freeze events. Central to this response is the plasma membrane, where low-temperature is perceived and cellular homeostasis must be preserved by maintaining membrane integrity. Here, we present the first plasma membrane proteome of cold-acclimatedBrachypodium distachyon, a model species for the study of monocot crops. A time course experiment investigated cold acclimation-induced changes in the proteome following two-phase partitioning plasma membrane enrichment and label-free quantification by nano-liquid chromatography mass spectrophotometry. Two days of cold acclimation were sufficient for membrane protection as well as an initial increase in sugar levels, and coincided with a significant change in the abundance of 154 proteins. Prolonged cold acclimation resulted in further increases in soluble sugars and abundance changes in more than 680 proteins, suggesting both a necessary early response to low-temperature treatment, as well as a sustained cold acclimation response elicited over several days. A meta-analysis revealed that the identified plasma membrane proteins have known roles in low-temperature tolerance, metabolism, transport, and pathogen defense as well as drought, osmotic stress and salt resistance suggesting crosstalk between stress responses, such that cold acclimation may prime plants for other abiotic and biotic stresses. The plasma membrane proteins identified here present keys to an understanding of cold tolerance in monocot crops and the hope of addressing economic losses associated with modern climate-mediated increases in frost events.
In vivo Analysis Reveals that ATP-hydrolysis Couples Remodeling to SWI/SNF Release from Chromatin
Authors: Tilly Ben C. , Chalkley Gillian E. , van der Knaap Jan A. , Moshkin Yuri M. , Kan Tsung Wai , Dekkers Dick H. W. , Demmers Jeroen A. A. , Verrijzer C. Peter
Published: April 2021

ATP-dependent chromatin remodelers control the accessibility of genomic DNA through nucleosome mobilization. However, the dynamics of genome exploration by remodelers, and the role of ATP hydrolysis in this process remain unclear. We used live-cell imaging ofDrosophilapolytene nuclei to monitor Brahma (BRM) remodeler interactions with its chromosomal targets. In parallel, we measured local chromatin condensation and its effect on BRM association. Surprisingly, only a small portion of BRM is bound to chromatin at any given time. BRM binds decondensed chromatin but is excluded from condensed chromatin, limiting its genomic search space. BRM-chromatin interactions are highly dynamic, whereas histone-exchange is limited and much slower. Intriguingly, loss of ATP hydrolysis enhanced chromatin retention and clustering of BRM, which was associated with reduced histone turnover. Thus, ATP hydrolysis couples nucleosome remodeling to remodeler release, driving a continuous transient probing of the genome.
Investigating genetic drivers of juvenile dermatomyositis pathogenesis using bioinformatics methods
Authors: Wang Kai , Zhang Zhongyuan , Meng Deqian , Li Ju
Published: April 2021

Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. The pathogenic mechanisms remain ill‐defined. The purpose of this study was to identify key genes related to JDM. Microarray datasets were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEG) were identified. Then, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and protein–protein interaction (PPI) network were carried out. In addition, the hub genes were selected by cytoHubba. The expression profile and diagnostic capacity (receiver–operator curve [ROC]) of interested hub genes were verified. Gene set enrichment analysis (GSEA) was also carried out. Moreover, the signature of hub genes was then used as a search query to explore the Connectivity Map (CMAP). A total of 128 DEG were identified. The enriched functions and pathways of the DEG include response to virus, negative regulation of cell migration, cadmium ion transmembrane transport, defense response to Gram‐negative bacterium, positive regulation of megakaryocyte differentiation, and negative regulation of angiogenesis. Twenty‐one hub genes were identified. The expression levels of the interested genes were also confirmed. ROC analysis confirmed that the expression of these genes can distinguish JDM from controls. GSEA showed that these genes are mainly related to “inflammatory response”, “complement”, “interferon‐α response”, “IL6/JAK/STAT3 signaling”, “TGF‐β signaling”, “IL2/STAT5 signaling” and “TNF‐α signaling via NF‐κB”. The CMAP research found some compounds with the potential to counteract the effects of the dysregulated molecular signature in JDM. In this study, bioinformatics methods were used to identify DEG, which helps us understand the molecular mechanisms of JDM and provide candidate targets for diagnosis and treatment of JDM.
Atorvastatin reverses high cholesterol‐induced cardiac remodelling and regulates mitochondrial quality‐control in a cholesterol‐independent manner: An experimental study
Authors: Zheng Peng , Ding Yanzi , Lu Feiyan , Liu Nannan , Wu Hengfang , Bian Zhiping , Chen Xiangjian , Yang Di
Published: April 2021

Mitochondria are key regulators of cell fate, maintaining self‐stability by a fine‐tuned quality‐control network including mitophagy, biogenesis, fission and fusion processes. Myocardial mitochondria can be impaired by hypercholesterolemia. Statins, such as atorvastatin, are considered the cornerstone in the management of hypercholesterolaemia primarily due to their marked cholesterol‐lowering ability. The direct effect of atorvastatin on myocardial mitochondria remains unclear. We aimed to explore whether atorvastatin could attenuate myocardial mitochondrial defects induced by high cholesterol, and whether cycloastragenol, a potent telomerase activator, could be used as a potential complementary bioactive compound for obesity and hypercholesterolaemia treatment. We found that atorvastatin at a low dose (3 mg/kg) did not reduce elevated serum cholesterol, but reversed cardiac remodelling and dysfunction in C57BL/6J mice fed with high‐fat diet (HFD). Atorvastatin reversed the upregulated mitophagy, mitochondrial fission and fusion, accompanied by mitochondrial biogenesis activation in HFD‐fed mice hearts. Mitochondrial structural impairments were attenuated by atorvastatin in HFD‐fed mice and oxidized low‐density lipoprotein (ox‐LDL) exposed HL‐1 cardiomyocytes. The depolarized mitochondrial membrane potential and increased mitochondrial oxygen consumption rates in ox‐LDL exposed HL‐1 cells were recovered by atorvastatin. Furthermore, atorvastatin co‐treated with cycloastragenol had better effects on reducing body weight, improving cardiac remodelling and dysfunction, and protecting mitochondria in high cholesterol. Conclusively, low‐dose atorvastatin exhibited a cholesterol‐independent cardioprotective effect through improving the mitochondrial quality‐control network and repairing mitochondrial ultrastructure in high cholesterol. Atorvastatin plus cycloastragenol supplement therapy has a better effect on treating obesity and hypercholesterolaemia.
Stereotactic body radiotherapy in the management of hepatocellular carcinoma: An Australian multi‐institutional patterns of practice review
Authors: Liu Howard Yu‐hao , Lee Yoo‐young Dominique , Sridharan Swetha , Choong Ee Siang , Le Hien , Wang Wei , Khor Richard , Chu Julie , Oar Andrew , Mott Rebekah , Smart Joanne , Jenkins Trish , Anderson Nigel , Cross Shamira , Loo Kee Fong , Wigg Alan , Stuart Katherine , Pryor David
Published: April 2021

Introduction

Stereotactic body radiotherapy (SBRT) is an emerging, therapeutic option in the management of hepatocellular carcinoma (HCC). A multicentre Liver Ablative Stereotactic Radiation (LASR) database was established to provide a collaborative platform for Australian institutions to define the practice of liver SBRT for HCC. This study explores the patterns of SBRT practice amongst Australian institutions.

Methods

This was a multi‐institutional retrospective study of patients treated with SBRT for HCC at 10 institutions between January 2013 and December 2019. Patients' demographics, disease characteristics and SBRT details were evaluated.

Results

Three hundred and seventeen patients were evaluated with a median age of 67 years (range, 32–90). Liver cirrhosis was present in 88.6%, baseline Child‐Pugh score was A5/6 in 85.1% and B7/8 in 13.2%. Median size of HCC treated was 30 mm (range, 10–280). 63.1% had early‐stage disease (Barcelona clinic liver cancer (BCLC) stage 0/A) and 36% had intermediate/advanced‐stage disease (BCLC B/C). In 2013/2014, six courses of SBRT were delivered, increasing to 108 in 2019. SBRT was prescribed in five fractions for 71.3% of the cohort. The most common dose fractionation schedule was 40 Gy in five fractions (24.3%). Median biologically effective dose (BED10) delivered was 85.5 Gy for early‐stage and 60 Gy for intermediate/advanced disease, respectively. The most common prescription range was 100–120 Gy BED10 (32.8%).

Conclusion

SBRT utilisation for HCC is increasing in Australia. There was wide variation in size of tumours and disease stages treated, and prescription patterns. Uniform reporting of clinical and dosimetric details are important in refining the role of liver SBRT.
Chromosomal‐scale genome assembly of Eleutherococcus senticosus provides insights into chromosome evolution in Araliaceae
Authors: Yang Zijiang , Chen Shanshan , Wang Shufen , Hu Ying , Zhang Guanghui , Dong Yang , Yang Shengchao , Miao Jianhua , Chen Wei , Sheng Jun
Published: April 2021

Siberian ginseng (Eleutherococcus senticosus, also known as ciwujia) belongs to the Araliaceae family, which contains more than 1,500 species in 41 genera with diverse chromosome numbers and genome sizes. General consensus posits that ancient whole‐genome duplication events and rapid evolutionary radiation are the driving forces for this variation in genome properties. In an attempt to generate more genomic information for the Araliaceae family, we report a 1.30 Gb high‐quality draft genome assembly (contig N50 = 309.43 kb) of E. senticosus via PacBio long reads and Hi‐C chromatin interaction maps. We found that transposable elements accounted for 72.82% of the genome and a total of 36,372 protein‐coding genes were predicted. Comparative analyses of the E. senticosus, Panax notoginseng and Daucus carota genomes revealed a burst expansion of Tekay chromoviral elements in Araliaceae after its divergence with Apiaceae. We also found that E. senticosus underwent a lineage‐specific whole‐genome duplication event Es‐α and a whole‐genome duplication event Araliaceae‐β that was probably shared by all Araliaceae species. Even though the rediploidization of the E. senticosus genome is evident, pathway analyses show that these two whole‐genome duplication events may have contributed to the adaptation of E. senticosus to a cold environment. Taken together, the high‐quality genome assembly of E. senticosus provides a valuable genomic resource for future research on the evolution of Araliaceae.
Decision‐to‐delivery interval and neonatal outcomes for category‐1 caesarean sections during the COVID‐19 pandemic
Authors: Bhatia K. , Columb M. , Bewlay A. , Tageldin N. , Knapp C. , Qamar Y. , Dooley A. , Kamath P. , Hulgur M. ,   collaborators
Published: April 2021

General anaesthesia is known to achieve the shortest decision‐to‐delivery interval for category‐1 caesarean section. We investigated whether the COVID‐19 pandemic affected the decision‐to delivery interval and influenced neonatal outcomes in patients who underwent category‐1 caesarean section. Records of 562 patients who underwent emergency caesarean section between 1 April 2019 and 1 July 2019 in seven UK hospitals (pre‐COVID‐19 group) were compared with 577 emergency caesarean sections performed during the same period during the COVID‐19 pandemic (1 April 2020–1 July 2020) (post‐COVID‐19 group). Primary outcome measures were: decision‐to‐delivery interval; number of caesarean sections achieving decision‐to‐delivery interval < 30 min; and a composite of adverse neonatal outcomes (Apgar 5‐min score < 7, umbilical arterial pH < 7.10, neonatal intensive care unit admission and stillbirth). The use of general anaesthesia decreased significantly between the pre‐ and post‐COVID‐19 groups (risk ratio 0.48 (95%CI 0.37–0.62); p < 0.0001). Compared with the pre‐COVID‐19 group, the post‐COVID‐19 group had an increase in median (IQR [range]) decision‐to‐delivery interval (26 (18–32 [4–124]) min vs. 27 (20–33 [3–102]) min; p = 0.043) and a decrease in the number of caesarean sections meeting the decision‐to‐delivery interval target of < 30 min (374/562 (66.5%) vs. 349/577 (60.5%); p = 0.02). The incidence of adverse neonatal outcomes was similar in the pre‐ and post‐COVID‐19 groups (140/568 (24.6%) vs. 140/583 (24.0%), respectively; p = 0.85). The small increase in decision‐to‐delivery interval observed during the COVID‐19 pandemic did not adversely affect neonatal outcomes.
Application of the indocyanine green fluorescence imaging method in laparoscopic resection of a solitary retroperitoneal metastasis of renal cell carcinoma: A case report
Authors: Kim Chul Jang , Nishida Masanari , Hanada Eiki , Kageyama Susumu , Narita Mitsuhiro , Kawauchi Akihiro
Published: April 2021

Fluorescence image‐guided surgery has improved intraoperative identification of anatomic structures including visualization of vascular anatomy. Herein, indocyanine green (ICG) fluorescence imaging was applied to identify of a recurrent small tumor of renal cell carcinoma (RCC) during laparoscopic surgery. The patient underwent left laparoscopic radical nephrectomy via the retroperitoneal approach for RCC (clear cell carcinoma, pT1bN0M0) at the age of 39 years. A solitary retroperitoneal mass (14 mm in diameter) was identified in a computed tomography scan 6 years after surgery. We performed laparoscopic resection with the application of the ICG angiography, because RCC is recognized as one of the most hypervascular cancers. The tumor was clearly visualized by fluorescence. Histopathological diagnosis of the resected tumor was recurrent RCC (low grade, G1). The patient remained free of disease at 2 years after surgery. The ICG fluorescence imaging would be a useful method for identification of metastatic small lesions of RCC during laparoscopic surgery.
Do goal cue and motor activity impact preschoolers’ working memory?
Authors: Fitamen Christophe , Blaye Agnès , Camos Valérie
Published: April 2021

Preschoolers are well known for their poor working memory (WM) performance. This could result from goal neglect, which would hamper the setting of maintenance strategies. Previous studies have shown that preschoolers’ WM performance can be improved in game‐like tasks, because they provide cues to support goal maintenance. However, in these studies, it was unclear what features of the task (either the main toy or the motor activity required by the game) provide efficient cues. The aim of the present study was to disentangle the two features to examine cue effects in 5‐ to 7‐year‐old children. No improvement of WM performance was observed when the toy was a potential goal cue, whereas the motor activity had a detrimental effect in all age groups. The latter effect could result from a distraction of attention from attention‐based maintenance activities. Hence, preschoolers' poor WM performance would not be fundamentally due to goal neglect.