bluuebunny/crossref_metadata_2025 huggingface dataset:
Gut microbiota analyses of Saudi populations for type 2 diabetes-related phenotypes reveals significant association
Authors: Al-Muhanna Fahd A , Dodwell Alexa K. , Al Eleq Abdulmohsen H , Albaker Waleed I , Brooks Andrew W. , Al-Sultan Ali I , Al-Rubaish Abdullah M , Alkharsah Khaled R , Sulaiman Raed M , Al-Quorain Abdulaziz A , Cyrus Cyril , Alali Rudaynah A , Vatte Chittibabu , Robinson Fred L. , Nguyen Carrie , Zhou Xin , Snyder Michael P. , Almuhanna Afnan F , Keating Brendan J , Piening Brian D. , Al-Ali Amein K
Published: October 2021

Large-scale gut microbiome sequencing has revealed key links between microbiome dysfunction and metabolic diseases such as T2D. To date, these efforts have largely focused on Western populations, with few studies assessing T2D microbiota associations in Middle Eastern communities where T2D prevalence is now over 20%. We analyzed the composition of stool 16S rRNA from 461 T2D and 119 non-T2Dparticipants from the Eastern Province of Saudi Arabia. We quantified the abundance of microbial communities to examine any significant differences between subpopulations of samples based on diabetes status and glucose level. We observed overall positive enrichment within diabetics compared to healthy individuals and amongst diabetic participants; those with high glucose levels exhibited slightly more positive enrichment compared to those at lower risk of fasting hyperglycemia. In particular, the genus Firmicutes was upregulated in diabetic participants compared to non-diabetic participants, and T2D was associated with an elevated Firmicutes/Bacteroidetes ratio, consistent with previous findings. Based on diabetes status and glucose levels of Saudi participants, relatively stable differences in stool composition were perceived by differential abundance and alpha diversity measures.

Author summary

The rates of Type 2 diabetes (T2D) in Saudi Arabia have risen dramatically in the last several decades due to socio-economic changes resulting in changes in dietary and sedentary lifestyles. This emergence has grown more rapidly and affects larger proportions of the population with estimates of T2D prevalence impacting 25% of the population. There is a paucity of microbiome data from Middle Eastern populations, and previous studies have been conducted on small sample sizes. Here we report on the first-ever characterization of gut microbiota T2D versus non-T2D and largest microbiome study ever conducted in a Middle Eastern country. The datasets from this study are important to create a regional reference T2D-microbiome catalogue which will propel the understanding of regional gut flora which are associated with T2D development. Based on T2D status and quantified glucose levels of Middle Eastern participants, relatively stable differences in stool composition were observed by differential abundance and alpha diversity measures. Comparing overlapping and varying patterns in gut microbiota with other studies is critical to assessing novel treatment options in light of a rapidly growing T2D health epidemic.
Comprehensive analysis of the circadian nuclear and cytoplasmic transcriptome in mouse liver
Authors: Hurni Clémence , Weger Benjamin , Gobet Cédric , Naef Felix
Published: October 2021

In eukaryotes, RNA is synthesised in the nucleus, spliced, and exported to the cytoplasm where it is translated and finally degraded. Any of these steps could be subject to temporal regulation during the circadian cycle, resulting in daily fluctuations of RNA accumulation and affecting the distribution of transcripts in different subcellular compartments. Our study analysed the nuclear and cytoplasmic, poly(A) and total transcriptomes of mouse livers collected over the course of a day. These data provide a genome-wide temporal inventory of enrichment in subcellular RNA, and revealed specific signatures of splicing, nuclear export and cytoplasmic mRNA stability related to transcript and gene lengths. Combined with a mathematical model describing rhythmic RNA profiles, we could test the rhythmicity of export rates and cytoplasmic degradation rates of approximately 1400 genes. With nuclear export times usually much shorter than cytoplasmic half-lives, we found that nuclear export contributes to the modulation and generation of rhythmic profiles of 10% of the cycling nuclear mRNAs. This study contributes to a better understanding of the dynamic regulation of the transcriptome during the day-night cycle.
MeDUsA: A novel system for automated axon quantification to evaluate neuroaxonal degeneration
Authors: Nitta Yohei , Kawai Hiroki , Osaka Jiro , Hakeda-Suzuki Satoko , Nagai Yoshitaka , Doubková Karolína , Suzuki Takashi , Tavosanis Gaia , Sugie Atsushi
Published: October 2021

Background

Drosophila is an excellent model organism for studying human neurodegenerative diseases (NDs), and the rough eye phenotype (REP) assay is a convenient experimental system for analysing the toxicity of ectopically expressed human disease genes. However, the association between REP and axonal degeneration, an early sign of ND, remains unclear. To address this question, we developed a method to evaluate axonal degeneration by quantifying the number of retinal R7 axons in Drosophila; however, it requires expertise and is time-consuming. Therefore, there is a need for an easy-to-use software that can automatically quantify the axonal degeneration.

Result

We created MeDUsA (a ‘method for the quantification of degeneration using fly axons’), which is a standalone executable computer program based on Python that combines a pre-trained deep-learning masking tool with an axon terminal counting tool. This software automatically quantifies the number of axons from a confocal z-stack image series. Using this software, we have demonstrated for the first time directly that axons degenerate when the causative factors of NDs (αSyn, Tau, TDP-43, HTT) were expressed in the Drosophila eye. Furthermore, we compared axonal toxicity of the representative causative genes of NDs and their pathological alleles with REP and found no significant correlation between them.

Conclusions

MeDUsA rapidly and accurately quantifies axons in Drosophila eye. By simplifying and automating time-consuming manual efforts requiring significant expertise, it enables large-scale, complex research efforts on axonal degeneration, such as screening to identify genes or drugs that mediate axonal toxicity caused by ND disease proteins.
Genomic adaptation of the picoeukaryote Pelagomonas calceolata to iron-poor oceans revealed by a chromosome-scale genome sequence
Authors: Guérin Nina , Ciccarella Marta , Flamant Elisa , Frémont Paul , Mangenot Sophie , Istace Benjamin , Noel Benjamin , Romac Sarah , Bachy Charles , Gachenot Martin , Pelletier Eric , Alberti Adriana , Jaillon Olivier , Cruaud Corinne , Wincker Patrick , Aury Jean-Marc , Carradec Quentin
Published: October 2021

The smallest phytoplankton species are key actors in oceans biogeochemical cycling and their abundance and distribution are affected with global environmental changes. Picoalgae (cells <2µm) of the Pelagophyceae class encompass coastal species causative of harmful algal blooms while others are cosmopolitan and abundant in open ocean ecosystems. Despite the ecological importance of Pelagophytes, only a few genomic references exist limiting our capacity to identify them and study their adaptation mechanisms in a changing environment. Here, we report the complete chromosome-scale assembled genome sequence of Pelagomonas calceolata. We identified unusual large low-GC and gene-rich regions potentially representing centromeres. These particular genomic structures could be explained by the absence of genes from a recombination pathway involving double Holiday Junctions. We identified a large repertoire of genes involved in inorganic nitrogen sensing and uptake and several genes replacing iron-requiring proteins potentially explaining P. calceolata ecological success in oligotrophic waters. Finally, based on this high-quality assembly, we evaluated P. calceolata relative abundance in all oceans using environmental Tara Oceans datasets. Our results suggest that P. calceolata is one of the most abundant eukaryotic species in the oceans with a relative abundance favoured by high temperature and iron-poor conditions. Climate change projections based on its relative abundance suggest an extension of the P. calceolata habitat toward the poles at the end of this century. Collectively, these findings reveal the ecological importance of P. calceolata and lay the foundation for a global scale analysis of the adaptation and acclimation strategies of picoalgae in a changing environment.
Identifying barriers to gene flow and hierarchical conservation units from seascape genomics: a modelling framework applied to a marine predator
Authors: Boussarie Germain , Momigliano Paolo , Robbins William D. , Bonnin Lucas , Cornu Jean-François , Fauvelot Cécile , Kiszka Jeremy J. , Manel Stéphanie , Mouillot David , Vigliola Laurent
Published: October 2021

The ongoing decline of large marine vertebrates must be urgently mitigated, particularly under increasing levels of climate change and other anthropogenic pressures. However, characterizing the connectivity among populations remains one of the greatest challenges for the effective conservation of an increasing number of endangered species. Achieving conservation targets requires an understanding of which seascape features influence dispersal and subsequent genetic structure. This is particularly challenging for adult-disperser species, and when distribution-wide sampling is difficult. Here, we developed a two-step modelling framework to investigate how seascape features drive the genetic connectivity of marine species without larval dispersal, to better guide the design of marine protected area networks and corridors. We applied this framework to the endangered grey reef shark, Carcharhinus amblyrhynchos, a reef-associated shark distributed across the tropical Indo-Pacific. In the first step, we developed a seascape genomic approach based on isolation-by-resistance models involving circuit theory applied to 515 shark samples, genotyped for 4,491 nuclear single-nucleotide polymorphisms, to explore which parameters drive their population genetic differentiation. We show that deep oceanic areas act as strong barriers to dispersal, while proximity to habitat facilitates dispersal. In the second step, we predicted the resulting genetic differentiation across the entire distribution range of the species, providing both local and global-scale conservation units for future management guidance. We found that grey reef shark populations are more fragmented than expected for such a mobile species, raising concerns about the resilience of isolated populations under high anthropogenic pressures. We recommend the use of this framework to identify barriers to gene flow and to help in the delineation of conservation units at different scales, together with its integration across multiple species when considering marine spatial planning.
Muscle systems and motility of early animals highlighted by cnidarians from the basal Cambrian
Authors: Wang Xing , Vannier Jean , Yang Xiaoguang , Leclère Lucas , Ou Qiang , Song Xikun , Komiya Tsuyoshi , Han Jian
Published: October 2021

Although fossil evidence suggest that various animal groups were able to move actively through their environment in the early stages of their evolution, virtually no direct information is available on the nature of their muscle systems. The origin of jellyfish swimming, for example, is of great concern to biologists. Exceptionally preserved muscles are described here in benthic peridermal olivooid medusozoans from the basal Cambrian of China (Kuanchuanpu Formation, ca. 535 Ma) that have direct equivalent in modern medusozoans. They consist of circular fibers distributed over the bell surface (subumbrella) and most probably have a myoepithelial origin. This is the oldest record of a muscle system in cnidarians and more generally in animals. This basic system was probably co-opted by younger early Cambrian jellyfish to develop capacities for the jet-propelled swimming within the water column. Additional lines of fossil evidence obtained from ecdysozoans (worms and panarthropods) show that the muscle systems of early animals underwent a rapid diversification through the early Cambrian and increased their capacity to colonize a wide range of habitats both within the water column and sediment at a critical time of their evolutionary radiation.
Alternative strategy to induce CRISPR-mediated genetic changes in hematopoietic cells
Authors: González-Romero E , Rosal-Vela A , Liquori A , Martínez-Valiente C , García-García G , Millán JM , Sanz MA , Cervera JV , Vázquez-Manrique RP
Published: October 2021

Acute Myeloid Leukaemia is a complex heterogenous disease caused by clonal expansion of undifferentiated myeloid precursors. Recently, several haematological models have been developed with CRISPR/Cas9, using viral vectors, because blood cells are hard to transfect. To avoid virus disadvantages, we have developed a strategy to generate CRISPR constructs, by means of PCR, which any lab equipped with basic technology can implement. These PCR-generated constructs enter easily into hard-to-transfect cells. After testing its functionality by editing MYBL2 gene in HEK293 cells, we successfully introduced the R172 mutation in IDH2 gene in NB4 cells that expresses constitutively the Cas9 nuclease. Comparing our methodology with ribonucleoprotein strategies, we found that mutation introduction efficiency was similar between both methodologies, and no off-target events were detected. Our strategy represents a valid alternative to introduce desired mutations in hard to transfect leukemic cells, avoiding using huge vectors or viral transduction.
A novel single-cell RNA-sequencing platform and its applicability connecting genotype to phenotype in ageing-disease
Authors: Shomroni Orr , Sitte Maren , Schmidt Julia , Parbin Sabnam , Ludewig Fabian , Yigit Gökhan , Zelarayan Laura Cecilia , Streckfuss-Bömeke Katrin , Wollnik Bernd , Salinas Gabriela
Published: October 2021

Advances in single cell multi-omics analysis such as the ability of a genotype to show phenotypic diversity lead to a comprehensive understanding of cellular events in human diseases. The cardinal feature to access this information is the technology used for single-cell isolation, barcoding, and sequencing. While numerous platforms have been reported for single-cell RNA-sequencing, technical enhancements are needed in terms of highly purified single cell selection, cell documentation or limitations in cell sizing and chemistry. In this study, we present a novel high-throughput platform using a full-length RNA-sequencing approach that offers substantial technical improvements of all parameters. We applied this platform to dermal fibroblasts derived from six patients with different segmental progeria syndromes and defined phenotype-associated pathway signatures and variant-associated expression modifiers. These results validate the applicability of our platform to highlight genotype–expression relationships for molecular phenotyping in ageing disorders.
Profiling RT-LAMP tolerance of sequence variation for SARS-CoV-2 RNA detection
Authors: Tamanaha Esta , Zhang Yinhua , Tanner Nathan A.
Published: October 2021

The ongoing SARS-CoV-2 pandemic has necessitated a dramatic increase in our ability to conduct molecular diagnostic tests, as accurate detection of the virus is critical in preventing its spread. However, SARS-CoV-2 variants continue to emerge, with each new variant potentially affecting widely-used nucleic acid amplification diagnostic tests. RT-LAMP has emerged as a quick, inexpensive diagnostic alternative to RT-qPCR, but has not been studied as thoroughly. Here we interrogate the effect of SARS-CoV-2 sequence mutations on RT-LAMP amplification, creating 572 single point mutation “variants” covering every position of the LAMP primers in 3 SARS-CoV-2 assays and analyzing their effects with over 4,500 RT-LAMP reactions. Remarkably, we observed only minimal effects on amplification speed and no effect on detection sensitivity, highlighting RT-LAMP as an extremely robust technique for viral RNA detection. Additionally, we describe the use of molecular beacons to sensitively identify variant RNA sequences. Together these data add to the growing body of knowledge on the utility of RT-LAMP and increase its potential to further our ability to conduct molecular diagnostic tests outside of the traditional clinical laboratory environment.
Treatment of waste stabilization pond effluent using natural zeolite for irrigation potential
Authors: Meiramkulova Kulyash , Mkilima Timoth , Kydyrbekova Aliya , Bukenova Elmira , Meirbekov Abdilda , Saspugayeva Gulnur , Adilbektegi Gulmira , Beisembayeva Kulzhan , Tazhkenova Gaukhar
Published: October 2021

Direct utilization of treated effluent from natural treatment systems for irrigation can be challenging on sensitive plants due to high levels of salinity. Post-treatment of such an effluent prior to its applicability in irrigation can be of significant importance. In this study, the wastewater from a natural treatment plant was treated using a lab-scale filtration system with zeolite as a filter material. Three different column depths (0.5 m, 0.75 m, and 1 m) were used to investigate the effect of column depth on the treatment efficiency of the media. The suitability of the raw wastewater and the treated effluent from each column for irrigation purposes was investigated. The water quality parameters investigated were; electrical conductivity (EC), total dissolved solids (TDS), sodium (Na+), calcium (Ca2+), and magnesium (Mg2+). From the analysis results, it was observed that the column depth had a significant influence on the removal efficiency of the pollutants. Where the removal efficiency was observed to be increasing with the increase in the column depth. The highest removal efficiency (94.58%) was achieved from the combination of electrical conductivity and 1 m column depth, while the lowest removal efficiency (10.05%) was observed from the combination of calcium and 0.5 m column depth. The raw wastewater fell mostly into a “very high” hazard, which is class four (C4) based on electrical conductivity and class four (S4) based sodium adsorption ratio; making it unsuitable for irrigation purposes. However, the status improved after the treatment using different column depths.
Designing Biological Micro-Sensors with Chiral Nematic Liquid Crystal Droplets
Authors: Honaker Lawrence W. , Chen Chang , Dautzenberg Floris M.H. , Brugman Sylvia , Deshpande Siddharth
Published: October 2021

Biosensing using liquid crystals has a tremendous potential by coupling the high degree of sensitivity of their alignment to their surroundings with clear optical feedback. Many existing set-ups use birefringence of nematic liquid crystals, which severely limits straightforward and frugal implementation into a sensing platform due to the sophisticated optical set-ups required. In this work, we instead utilize chiral nematic liquid crystal micro-droplets, which show strongly reflected structural colour, as sensing platforms for surface active agents. We systematically quantify the optical response of closely related biological amphiphiles and find unique optical signatures for each species. We detect signatures across a wide range of concentrations (from μM to mM), with fast response times (from seconds to minutes). The striking optical response is a function of the adsorption of surfactants in a non-homogeneous manner and the topology of the liquid crystal orientation at the interface requiring a scattering, multidomain structure, which we observe to be different between molecules. We show lab-on-a-chip capability of our method by drying droplets in high-density two-dimensional arrays and simply hydrating the chip to detect dissolved analytes. Finally, we show proof-of-principle in vivo biosensing in the intestinal tracts of live zebrafish larvae, demonstrating CLC droplets show a clear and differential optical response between healthy and inflamed tissues. Our unique approach has great potential in developing on-site detection platforms and detecting biological amphiphiles in living organisms.
The Wernicke conundrum revisited: evidence from connectome-based lesion-symptom mapping
Authors: Matchin William , den Ouden Dirk-Bart , Hickok Gregory , Hillis Argye E. , Bonilha Leonardo , Fridriksson Julius
Published: October 2021

Wernicke’s area has been assumed since the 1800s to be the primary region supporting word and sentence comprehension. However, Mesulam et al. (2015; 2019) raised what they termed the ‘Wernicke conundrum’, noting widespread variability in the anatomical definition of this area and presenting data from primary progressive aphasia that challenged this classical assumption. To resolve the conundrum, they posited a ‘double disconnection’ hypothesis: that word and sentence comprehension deficits in stroke-based aphasia result from disconnection of anterior temporal and inferior frontal regions from other parts of the brain due to white matter damage, rather than dysfunction of Wernicke’s area itself. To test this hypothesis, we performed lesiondeficit correlations, including connectome-based lesion-symptom mapping, in four large, partially overlapping groups of English-speaking chronic left hemisphere stroke survivors. After removing variance due to object recognition and associative semantic processing, the same middle and posterior temporal lobe regions were implicated in both word comprehension deficits and complex noncanonical sentence comprehension deficits. Connectome lesion-symptom mapping revealed similar temporal-occipital white matter disconnections for impaired word and noncanonical sentence comprehension, including the temporal pole. We found an additional significant temporal-parietal disconnection for noncanonical sentence comprehension deficits, which may indicate a role for phonological working memory in processing complex syntax, but no significant frontal disconnections. Moreover, damage to these middle-posterior temporal lobe regions was associated with both word and noncanonical sentence comprehension deficits even when accounting for variance due to the strongest anterior temporal and inferior frontal white matter disconnections, respectively. Our results largely agree with the classical notion that Wernicke’s area, defined here as middle superior temporal gyrus and middle-posterior superior temporal sulcus, supports both word and sentence comprehension, suggest a supporting role for temporal pole in both word and sentence comprehension, and speak against the hypothesis that comprehension deficits in Wernicke’s aphasia result from double disconnection.
Distinct Representations of Body and Head motion are Dynamically Encoded by Purkinje cell Populations in the Macaque Cerebellum
Authors: Zobeiri Omid A. , Cullen Kathleen E.
Published: October 2021

The ability to accurately control our posture and perceive spatial orientation during self-motion requires knowledge of the motion of both the head and body. However, whereas the vestibular sensors and nuclei directly encode head motion, no sensors directly encode body motion. Instead, the integration of vestibular and neck proprioceptive inputs is necessary to transform vestibular information into the body-centric reference frame required for postural control. The anterior vermis of the cerebellum is thought to play a key role in this transformation, yet how its Purkinje cells integrate these inputs or what information they dynamically encode during self-motion remains unknown. Here we recorded the activity of individual anterior vermis Purkinje cells in alert monkeys during passively applied whole-body, body-under-head, and head-on-body rotations. Most neurons dynamically encoded an intermediate representation of self-motion between head and body motion. Notably, these neurons responded to both vestibular and neck proprioceptive stimulation and showed considerable heterogeneity in their response dynamics. Furthermore, their vestibular responses demonstrated tuning in response to changes in head-on-body position. In contrast, a small remaining percentage of neurons sensitive only to vestibular stimulation unambiguously encoded head-in-space motion across conditions. Using a simple population model, we establish that combining responses from 40 Purkinje cells can explain the responses of their target neurons in deep cerebellar nuclei across all self-motion conditions. We propose that the observed heterogeneity in Purkinje cells underlies the cerebellum’s capacity to compute the dynamic representation of body motion required to ensure accurate postural control and perceptual stability in our daily lives.
Trimeric Photosystem I facilitates energy transfer from phycobilisomes in Synechocystis sp. PCC 6803
Authors: Akhtar Parveen , Biswas Avratanu , Balog-Vig Fanny , Domonkos Ildikó , Kovács László , Lambrev Petar H.
Published: October 2021

In cyanobacteria, phycobilisomes serve as peripheral light-harvesting complexes of the two photosystems, extending their antenna size and the wavelength range of photons available for photosynthesis. The abundance of phycobilisomes, the number of phycobiliproteins they contain, and their light-harvesting function are dynamically adjusted in response to the physiological conditions. Phycobilisomes are also thought to be involved in state transitions that maintain the excitation balance between the two photosystems. Unlike its eukaryotic counterpart, PSI is trimeric in many cyanobacterial species and the physiological significance of this is not well understood. Here we compared the composition and light-harvesting function of phycobilisomes in cells of Synechocystis sp. PCC 6803, which has primarily trimeric PSI, and the ΔpsaL mutant unable to form trimers. We also investigated a mutant additionally lacking the PsaJ and PsaF subunits of PSI. Both strains with monomeric PSI accumulated significantly more allophycocyanin per chlorophyll, indicating higher abundance of phycobilisomes. On the other hand, a higher phycocyanin:allophycocyanin ratio in WT suggests larger phycobilisomes or the presence of APC-less phycobilisomes (CpcL-type), that are not assembled in cells with monomeric PSI. Steady-state and time-resolved fluorescence spectroscopy at room temperature and 77 K revealed that PSII receives more energy from the phycobilisomes at the expense of PSI in cells with monomeric PSI, regardless of the presence of PsaF. Taken together, these results show that the oligomeric state of PSI has an impact on the excitation energy flow in Synechocystis.

One-sentence summary

Cyanobacterial mutants with monomeric PSI show changes in the composition and abundance of phycobilisomes and in the excitation energy transfer to PSII and PSI.
SCARECROW maintains the stem cell niche in Arabidopsis root by ensuring telomere integrity
Authors: Wang Bingxin , Shi Xiaowen , Gao Jingbo , Liao Rui , Fu Jing , Bai Juan , Cui Hongchang
Published: October 2021

Stem cells are the ultimate source of the cells in various tissues and organs, and thus are essential to postembryonic plant growth and development. SCARECROW (SCR) is a plant-specific transcription regulator well known for its role in stem-cell renewal in plant roots, but the mechanism by which SCR exerts this function is still unclear. To address this question, we carried out a genetic screen for mutants that no longer express SCR in the stem-cell niche in the Arabidopsis root, and one of the mutants is characterized herein. Using marker-assisted mapping, whole genome sequencing, and complementation tests, we pinpointed the causal mutation in this mutant at TEN1, which encodes telomere-end protecting factor. By sequence alignment of TEN1 homologs in a wide range of eukaryotes, we identified two novel motifs. The importance of these motifs was examined through site-directed mutagenesis of a conserved amino acid, and through complementation tests, which showed that G100 is required for TEN1 stability. Interestingly, we found that TEN1 expression was dramatically reduced in the scr mutant. Two components in the same protein complex as TEN1, STN1 and CTC1, were found to be also dramatically downregulated in scr, as well as telomerase. Further studies showed that loss of STN1, CTC1 and telomerase also caused defects in the root stem cells. In line with these findings, the scr mutant was hypersensitive to DNA damage reagents such as Zeocin. These results together suggest that SCR maintains root stem cells by promoting expression of genes that ensures genome integrity.

One sentence summary

This study reveals a role for the root development regulator SCARECROW in maintaining the expression of telomere-end protecting factors and a connection between genome integrity and stem-cell maintenance in Arabidopsis root.
Copper microRNAs govern the formation of giant feeding cells induced by the root knot nematode Meloidogyne incognita in Arabidopsis thaliana
Authors: Noureddine Yara , da Rocha Martine , Thomine Sébastien , Quentin Michaël , Abad Pierre , Favery Bruno , Jaubert-Possamai Stéphanie
Published: October 2021

miR408 and miR398 are two conserved microRNAs which expression is activated by the SPL7 transcription factor in response to copper starvation. We identified these two microRNAs families as upregulated in Arabidopsis thaliana and Solanum lycopersicum roots infected by root-knot nematodes. These endoparasites induce the dedifferentiation of a few root cells and the reprogramming of their gene expression to generate giant feeding cells. By combining functional approaches, we deciphered the signaling cascade involving these microRNAs, their regulator and their targets. MIR408 expression was located within nematode-induced feeding cells in which it co-localised with SPL7 expression and was regulated by copper. Moreover, infection assays with mir408 and spl7 KO mutants or lines expressing targets rendered resistant to cleavage by miR398 demonstrated the essential role of the SPL7/MIR408/MIR398 module in the formation of giant feeding cells. Our findings reveals how perturbation of plant copper homeostasis, via the SPL7/MIR408/MIR398 module, governs the formation of nematode-induced feeding cells.
Genomic analysis of a parasite invasion: colonization of the Americas by the blood fluke, Schistosoma mansoni
Authors: Platt Roy N. , Le Clec’h Winka , Chevalier Frédéric D. , McDew-White Marina , LoVerde Philip T. , de Assis Rafael R. , Oliveira Guilherme , Kinunghi Safari , Djirmay Amadou Garba , Steinauer Michelle L. , Gouvras Anouk , Rabone Muriel , Allan Fiona , Webster Bonnie L. , Webster Joanne P. , Emery Aidan , Rollinson David , Anderson Timothy J. C.
Published: October 2021

Schistosoma mansoni, a snail-vectored, blood fluke that infects humans, was introduced into the Americas from Africa during the Trans-Atlantic slave trade. As this parasite shows strong specificity to the snail intermediate host, we expected that adaptation to S. American Biomphalaria spp. snails would result in population bottlenecks and strong signatures of selection. We scored 475,081 single nucleotide variants (SNVs) in 143 S. mansoni from the Americas (Brazil, Guadeloupe, and Puerto Rico) and Africa (Cameroon, Niger, Senegal, Tanzania, and Uganda), and used these data to ask: (i) Was there a population bottleneck during colonization? (ii) Can we identify signatures of selection associated with colonization? And (iii) what were the source populations for colonizing parasites? We found a 2.4-2.9-fold reduction in diversity and much slower decay in linkage disequilibrium (LD) in parasites from East to West Africa. However, we observed similar nuclear diversity and LD in West Africa and Brazil, suggesting no strong bottlenecks and limited barriers to colonization. We identified five genome regions showing selection in the Americas, compared with three in West Africa and none in East Africa, which we speculate may reflect adaptation during colonization. Finally, we infer that unsampled African populations from central African regions between Benin and Angola, with contributions from Niger, are likely the major source(s) for Brazilian S. mansoni. The absence of a bottleneck suggests that this is a rare case of a serendipitous invasion, where S. mansoni parasites were preadapted to the Americas and were able to establish with relative ease.
In pursuit of biomarkers for predicting susceptibility to activity-based anorexia (ABA) in adolescent female rats
Authors: Milton Laura K , Patton Timothy , O’Keeffe Meredith , Oldfield Brian J , Foldi Claire J
Published: October 2021

Anorexia nervosa (AN) has high rates of mortality and low rates of recovery, with outcomes that worsen with illness duration. Improved early intervention strategies are required and identifying risk factors that contribute to the development of AN is critical to their implementation. The development of AN often follows a pre-existing diagnosis of anxiety disorders and obsessive-compulsive disorder and substantial genetic overlap between these conditions suggest common underlying features may predict vulnerability to AN. Moreover, patients with AN have increased levels of circulating proinflammatory cytokines, which may be involved in susceptibility to pathological weight loss considering that children with immune dysfunction have a higher risk of subsequent AN diagnoses.

Here, we used the activity-based anorexia (ABA) model to examine whether baseline levels of locomotion, anxiety-like behaviour, compulsive behaviour, and circulating immune markers predict the subsequent development of pathological weight loss in adolescent female rats. While none of these primary features were shown to differentiate rats that went on to be susceptible or resistant to weight loss in ABA, increased locomotion and anxiety-like behaviour were both associated with the extent of weight loss in susceptible but not resistant animals. Intriguingly, behaviour related to poor decision-making in a situation of conflict was shown to predict vulnerability to ABA. Future research using the ABA model to uncover early predictors of AN should focus on translationally relevant assays of decision-making and cognitive behaviour, dysfunction of which may not only predispose animals to ABA but may also represent an endophenotype linking anorectic, anxiety-like and compulsive behaviour.
Trisomy 21 increases microtubules and disrupts centriolar satellite localization
Authors: McCurdy Bailey L. , Jewett Cayla E. , Stemm-Wolf Alexander J. , Duc Huy Nguyen , Joshi Molishree , Espinosa Joaquin M. , Prekeris Rytis , Pearson Chad G.
Published: October 2021

Trisomy 21, the cause of Down syndrome, causes a 0.5-fold protein increase of the chromosome 21-resident gene Pericentrin (PCNT) and reduces primary cilia formation and signaling. Here we investigate the mechanisms by which PCNT imbalances disrupt cilia. Using isogenic RPE-1 cells with increased chromosome 21 dosage, we find PCNT protein accumulates around the centrosome as a pericentrosomal cluster of enlarged cytoplasmic puncta that localize along and at MT ends. Cytoplasmic PCNT puncta impact the intracellular MT trafficking network required for primary cilia, as the PCNT puncta sequester cargo peripheral to centrosomes in what we call pericentrosomal crowding. The centriolar satellite proteins, PCM1, CEP131 and CEP290, important for ciliogenesis, accumulate at sites of enlarged PCNT puncta in trisomy 21 cells. Reducing PCNT when chromosome 21 ploidy is elevated is sufficient to decrease PCNT puncta, reestablish a normal density of MTs around the centrosome, restore ciliogenesis to wild type levels and decrease pericentrosomal crowding. A transient reduction in MTs also decreases pericentrosomal crowding and partially rescues ciliogenesis in trisomy 21 cells, indicating that increased PCNT leads to defects in the microtubule network deleterious to normal centriolar satellite distribution. We propose that chromosome 21 aneuploidy disrupts MT-dependent intracellular trafficking required for primary cilia.

TOC

McCurdy et al explore why elevated Pericentrin in trisomy 21 negatively impacts primary cilia formation and signaling. They find that elevated Pericentrin produces more pericentrosomal puncta that associates with and increases microtubules. Changes to Pericentrin and microtubules mislocalizes centriolar satellites in a pericentrosomal crowd.
Temporal cell fate determination in the spinal cord is mediated by the duration of Notch signalling
Authors: Jacobs Craig T. , Kejriwal Aarti , Kocha Katrinka M. , Jin Kevin Y. , Huang Peng
Published: October 2021

During neural development, progenitor cells generate different types of neurons in specific time windows. Despite the characterisation of many of the transcription factor networks involved in these differentiation events, the mechanism behind their temporal regulation is poorly understood. To address this question, we studied the temporal differentiation of the simple lateral floor plate (LFP) domain in the zebrafish spinal cord. LFP progenitors sequentially generate early-born Kolmer-Agduhr” (KA”) interneurons and late-born V3 interneurons. Analysis using a Notch signalling reporter demonstrates that these cell populations have distinct Notch signalling profiles. Not only do V3 cells receive higher total levels of Notch response, but they collect this response over a longer duration compared to V3 cells. To test whether the duration of Notch signalling determines the temporal cell fate specification, we combined a transgene that constitutively activates Notch signalling in the ventral spinal cord with a heat shock inducible Notch signalling terminator to switch off Notch response at any given time. Sustained Notch signalling results in expanded LFP progenitors while KA” and V3 interneurons fail to specify. Early termination of Notch signalling leads to exclusively KA” cell fate, despite the high level of Notch signalling, whereas late attenuation of Notch signalling drives only V3 cell fate. This suggests that the duration of Notch signalling is instructive in cell fate specification. Interestingly, knockdown experiments reveal a role for the Notch ligand Jag2b in maintaining LFP progenitors and limiting their differentiation into KA” and V3 cells. Our results indicate that Notch signalling is required for neural progenitor maintenance while a specific attenuation timetable defines the fate of the postmitotic progeny.
Particle morphology of medusavirus inside and outside the cells reveals a new maturation process of giant viruses
Authors: Watanabe Ryoto , Song Chihong , Kayama Yoko , Takemura Masaharu , Murata Kazuyoshi
Published: October 2021

Medusavirus, a giant virus, is phylogenetically closer to eukaryotes than the other giant viruses and has been recently classified as an independent species. However, details of its morphology and maturation process in host cells remain unclear. Here, we investigated the particle morphology of medusavirus inside and outside infected cells using conventional transmission electron microscopy (C-TEM) and cryo-electron microscopy (cryo-EM). The C-TEM of amoeba infected with the medusavirus showed four types of particles: empty, DNA-full, and the corresponding intermediates. Time-dependent changes in the proportion and following intracellular localization of these particles suggested a new maturation process for the medusavirus. Empty particles and viral DNAs were produced independently in the cytoplasm and nucleus, respectively, and only empty particles located near the nucleus incorporated the viral DNA into the capsid. All four types of particles were also found outside the cells. The cryo-EM of these particles showed that the intact capsid structure, covered with three different types of spikes, was conserved among all particle types, although with minor size-related differences. The internal membrane exhibited a structural array similar to that of the capsid, interacted closely with the capsid, and displayed open membrane structures in the empty and empty-intermediate particles. This result suggests that the open structures in the internal membrane are used for an exchange of scaffold proteins and viral DNA during the maturation process. This new model of the maturation process of medusavirus provides insight into the structural and behavioral diversity of giant viruses.

Importance

Giant viruses exhibit diverse morphologies and maturation processes. In the present study, medusavirus showed four types of particle morphologies both inside and outside the infected cells, when propagated in the laboratory using amoeba culture. Time-course analysis of the medusavirus particles in the infected cells reveals a new maturation process. Empty viral particles and viral DNAs were produced independently in the cytoplasm and nucleus, and only the empty particles located near the nucleus incorporated the viral DNA. Consequently, many immature particles, along with mature virions, were released from the host cells. Except for showing a small change in size, the capsid structures were well preserved during the maturation process. The empty viral particles and corresponding intermediates showed open membrane structures, which are presumably used for exchanging scaffold proteins and viral DNAs.
Six-month sequelae of post-vaccination SARS-CoV-2 infection: a retrospective cohort study of 10,024 breakthrough infections
Authors: Taquet Maxime , Dercon Quentin , Harrison Paul J
Published: October 2021

Vaccination has proven effective against infection with SARS-CoV-2, as well as death and hospitalisation following COVID-19 illness. However, little is known about the effect of vaccination on other acute and post-acute outcomes of COVID-19. Data were obtained from the TriNetX electronic health records network (over 81 million patients mostly in the USA). Using a retrospective cohort study and time-to-event analysis, we compared the incidences of COVID-19 outcomes between individuals who received a COVID-19 vaccine (approved for use in the USA) at least 2 weeks before SARS-CoV-2 infection and propensity score-matched individuals unvaccinated for COVID-19 but who had received an influenza vaccine. Outcomes were ICD-10 codes representing documented COVID-19 sequelae in the 6 months after a confirmed SARS-CoV-2 infection (recorded between January 1 and August 31, 2021). Associations with the number of vaccine doses (1 vs. 2) and age (< 60 vs. ≥ 60 years-old) were assessed. Among 10,024 vaccinated individuals with SARS-CoV-2 infection, 9479 were matched to unvaccinated controls. Receiving at least one COVID-19 vaccine dose was associated with a significantly lower risk of respiratory failure, ICU admission, intubation/ventilation, hypoxaemia, oxygen requirement, hypercoagulopathy/venous thromboembolism, seizures, psychotic disorder, and hair loss (each as composite endpoints with death to account for competing risks; HR 0.70-0.83, Bonferroni-corrected p<.05), but not other outcomes, including long-COVID features, renal disease, mood, anxiety, and sleep disorders. Receiving 2 vaccine doses was associated with lower risks for most outcomes. Associations between prior vaccination and outcomes of SARS-CoV-2 infection were marked in those < 60 years-old, whereas no robust associations were observed in those ≥ 60 years-old. In summary, COVID-19 vaccination is associated with lower risk of several, but not all, COVID-19 sequelae in those with breakthrough SARS-CoV-2 infection. These benefits of vaccination were clear in younger people but not in the over-60s. The findings may inform service planning, contribute to forecasting public health impacts of vaccination programmes, and highlight the need to identify additional interventions for COVID-19 sequelae.
Glucose intolerance in aging is mediated by the Gpcpd1-GPC metabolic axis
Authors: Cikes Domagoj , Leutner Michael , Cronin Shane J.F. , Novatchkova Maria , Pfleger Lorenz , Klepochová Radka , Lair Benjamin , Lac Marlène , Bergoglio Camille , Viguerie Nathalie , Dürnberger Gerhard , Roitinger Elisabeth , Rullman Eric , Gustafsson Thomas , Hagelkruys Astrid , Tavernier Geneviève , Bourlier Virginie , Knauf Claude , Krebs Michael , Kautzky-Willer Alexandra , Moro Cedric , Krssak Martin , Orthofer Michael , Penninger Josef M.
Published: October 2021

Skeletal muscle plays a central role in the regulation of systemic metabolism during lifespan. With aging, muscle mediated metabolic homeostasis is perturbed, contributing to the onset of multiple chronic diseases. Our knowledge on the mechanisms responsible for this age-related perturbation is limited, as it is difficult to distinguish between correlation and causality of molecular changes in muscle aging. Glycerophosphocholine phosphodiesterase 1 (GPCPD1) is a highly abundant muscle enzyme responsible for the hydrolysis of the lipid glycerophosphocholine (GPC). The physiological function of GPCPD1 remained largely unknown. Here, we report that the GPCPD1-GPC metabolic pathway is dramatically perturbed in the aged muscle. Muscle-specific inactivation ofGpcpd1resulted in severely affected glucose metabolism, without affecting muscle development. This pathology was muscle specific and did not occur in white fat-, brown fat- and liver-deficientGpcpd1deficient mice. Moreover, in the muscle specific mutant mice, glucose intolerance was markedly accelerated under high sugar and high fat diet. Mechanistically,Gpcpd1deficiency results in accumulation of GPC, without any other significant changes in the global lipidome. This causes an “aged-like” transcriptomic signature in youngGpcpd1deficient muscles and impaired insulin signaling. Finally, we report that GPC levels are markedly perturbed in muscles from both aged humans and patients with Type 2 diabetes, with a high correlation between GPC levels and increased chronological age. Our findings show the novel and critical physiological function of GPCPD1-GPC metabolic pathway to glucose metabolism, and the perturbation of this pathway with aging, which may contribute to glucose intolerance in aging.