bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcellular second messenger networks drive distinct repellent-induced axon behaviors
Authors: Baudet S , Zagar Y , Roche F , Gomez Bravo C , Couvet S , Bécret J , Belle M , Ros O , Nicol X 
Published: February 2023

AbstractSecond messengers, including cAMP, cGMP and Ca2+are often placed in an integrating position to combine the extracellular cues that orient growing axons in the developing brain. This view suggests that axon repellents share the same set of cellular messenger signals and that axon attractants evoke opposite cAMP, cGMP and Ca2+changes. Investigating the confinement of these second messengers in cellular nanodomains, we instead demonstrate that two repellent cues, ephrin-A5 and Slit1, induce spatially segregated signals. These guidance molecules activate subcellular-specific second messenger crosstalks, each signaling network controlling distinct axonal morphology changesin vitroand pathfinding decisionsin vivo.
Aberrant light sensing and motility in the green algaChlamydomonas priscuiifrom the ice-covered Antarctic Lake Bonney
Authors: Poirier Mackenzie , Osmers Pomona , Wilkins Kieran , Morgan-Kiss Rachael M. , Cvetkovska Marina 
Published: February 2023

AbstractThe Antarctic green algaChlamydomonas priscuiiis an obligate psychrophile and an emerging model for photosynthetic adaptation to extreme conditions. Endemic to the ice-covered Lake Bonney, this alga thrives at highly unusual light conditions characterized by very low light irradiance (<15 μmol m-2s-1), a narrow wavelength spectrum enriched in blue light, and an extreme photoperiod. Genome sequencing ofC. priscuiiexposed an unusually large genome, with hundreds of highly similar gene duplicates and expanded gene families, some of which could be aiding its survival in extreme conditions. In contrast to the described expansion in the genetic repertoire inC. priscuii, here we suggest that the gene family encoding for photoreceptors is reduced when compared to related green algae. This alga also possesses a very small eyespot and exhibits an aberrant phototactic response, compared to the modelChlamydomonas reinhardtii. We also investigated the genome and behaviour of the closely related psychrophilic algaChlamydomonassp. ICE-MDV, that is found throughout the photic zone of Lake Bonney and is naturally exposed to higher light levels. Our analyses revealed a photoreceptor gene family and a robust phototactic response similar to those in the modelChlamydomonas reinhardtii. These results suggest that the aberrant phototactic response inC. priscuiiis a result of life under extreme shading rather than a common feature of all psychrophilic algae. We discuss the implications of these results on the evolution and survival of shade adapted polar algae.
OH 89: A newly described ∼1.8-million-year-old hominid clavicle from Olduvai Gorge
Authors: Taylor Catherine E , Masao Fidelis , Njau Jackson K , Songita Agustino Venance , Hlusko Leslea J 
Published: February 2023

AbstractObjectivesHere, we describe the morphology and geologic context of OH 89, a ∼1.8million-year-old partial hominid clavicle from Olduvai (Oldupai) Gorge, Tanzania. We compare the morphology and clavicular curvature of OH 89 to modern humans, extant apes, and a sample of other hominid fossil clavicles.Materials and MethodsComparative samples include 25 modern human clavicles, 30Gorilla, 31Pan, 7Papio, and five hominid clavicles. Length regression on midshaft size using the extant comparative samples is used to estimate the total length of OH 89. A set of 9 linear measurements are taken from each individual. We also describe a new methodology for measuring clavicular curvature using measurements of sternal and acromial curvature, from which an overall curvature measurement is calculated. A principal component analysis (PCA) and a t-distributed stochastic neighbor embedding (tSNE) analysis are used to compare the morphology of OH 89 with the extant and fossil comparative samples.ResultsOur new method of measuring clavicular curvature successfully separates the different genera of the extant clavicles. The length estimate and sternal and acromial curve measurements for OH 89 falls within the larger male humans. The PCA shows OH 89 and most of the fossil hominids falling between the modern human andPangroups, while the t-SNE suggests that OH 89, KSD-VP-1/1, KNM-ER 1808, and OH 48 are more similar to each other than to any of the other groups. This analysis also plots KNM-WT 15000 with the modern humans and Krapina 158 with thePanindividuals.DiscussionThe OH 89 clavicle derives from an individual of unknown hominid species with a shoulder breadth similar to that of a large human male. The curvature of OH 89 is relatively human-like relative to its length. Our new methodology for measuring clavicular curvature, combined with the utilization of t-SNE analyses and comparison of t-SNE results to PCA results, provides greater separation of genera than previously used methods, and wider use of t-SNE may be useful in paleoanthropological work.
Modelling the Erythroblastic Island Niche of Dyserythropoietic Anaemia Type IV patients using Induced Pluripotent Stem Cells
Authors: May Alisha , Ventura Telma , Fidanza Antonella , Volmer Helena , Taylor Helen , Romanò Nicola , D’Souza Sunita L , Bieker James J. , Forrester Lesley M. 
Published: February 2023

AbstractCongenital dyserythropoietic anaemia (CDA) type IV has been associated with an amino acid substitution, Glu325Lys (E325K), in the transcription factor KLF1. These patients present with a range of symptoms, including the persistence of nucleated red blood cells (RBCs) in the peripheral blood which reflects the known role for KLF1 within the erythroid cell lineage. The final stages of RBCs maturation and enucleation take place within the erythroblastic island (EBI) niche in close association with EBI macrophages. It is not known whether the detrimental effects of the E325K mutation in KLF1 are restricted to the erythroid lineage or whether deficiencies in macrophages associated with their niche also contribute to the disease pathology. To address this question, we generated anin vitromodel of the human EBI niche using induced pluripotent stem cells (iPSCs) derived from a CDA type IV patient as well as iPSCs genetically modified to express an KLF1-E325K-ERT2protein that could be activated with 4OH-tamoxifen. CDA patient-derived iPSCs and iPSCs expressing the activated KLF1-E325K-ERT2protein showed significant deficiencies in the production of erythroid cells with associated disruption of some known KLF1 target genes. Macrophages could be generated from all iPSC lines but when the E325K-ERT2fusion protein was activated, we noted the generation of a slightly less mature macrophage population marked by CD93. A subtle reduction in their ability to support RBC maturation was also associated with macrophages carrying the E325K-ERT2transgene. Taken together these data support the notion that the clinically significant effects of the KLF1-E325K mutation are primarily associated with deficiencies in the erythroid lineage but that deficiencies in the niche might have the potential to exacerbate the condition. The strategy we describe provides a powerful approach to assess the effects of other mutations in KLF1 as well as other factors associated with the EBI niche.
Noradrenaline release from the locus coeruleus shapes stress-induced hippocampal gene expression
Authors: Privitera Mattia , von Ziegler Lukas M. , Floriou-Servou Amalia , Duss Sian N. , Zhang Runzhong , Waag Rebecca , Leimbacher Sebastian , Sturman Oliver , Roessler Fabienne K. , Heylen Annelies , Vermeiren Yannick , Van Dam Debby , De Deyn Peter P. , Germain Pierre-Luc , Bohacek Johannes 
Published: February 2023

AbstractExposure to an acute stressor triggers a complex cascade of neurochemical events in the brain. However, deciphering their individual impact on stress-induced molecular changes remains a major challenge. Here we combine RNA-sequencing with selective pharmacological, chemogenetic and optogenetic manipulations to isolate the contribution of the locus coeruleus - noradrenaline (LC-NA) system to the acute stress response. We reveal that NA-release during stress exposure regulates a large and reproducible set of genes in the dorsal and ventral hippocampus via β-adrenergic receptors. For a smaller subset of these genes, we show that NA release triggered by LC stimulation is sufficient to mimic the stress-induced transcriptional response. We observe these effects in both sexes, and independent of the pattern and frequency of LC activation. Using a retrograde optogenetic approach, we demonstrate that hippocampus-projecting LC neurons directly regulate hippocampal gene expression. Overall, a highly selective set of astrocyte-enriched genes emerges as key targets of LC-NA activation, most prominently several subunits of protein phosphatase 1 (Ppp1r3c,Ppp1r3d,Ppp1r3g) and type II iodothyronine deiodinase (Dio2). These results highlight the importance of astrocytic energy metabolism and thyroid hormone signaling in LC-mediated hippocampal function and offer new molecular targets for understanding how NA impacts brain function in health and disease.
Glutaredoxin regulation of primary root growth is associated with early drought stress tolerance in pearl millet
Authors: de la Fuente Carla , Grondin Alexandre , Sine Bassirou , Debieu Marilyne , Belin Christophe , Hajjarpoor Amir , Atkinson Jonathan A. , Passot Sixtine , Salson Marine , Orjuela Julie , Tranchant-Dubreuil Christine , Brossier Jean-Rémy , Steffen Maxime , Morgado Charlotte , Dinh Hang Ngan , Pandey Bipin K. , Darmau Julie , Champion Antony , Petitot Anne-Sophie , Barrachina Celia , Pratlong Marine , Mounier Thibault , Nakombo-Gbassault Princia , Gantet Pascal , Gangashetty Prakash , Guédon Yann , Vadez Vincent , Reichheld Jean-Philippe , Bennett Malcolm J. , Kane Ndjido , Guyomarc’h Soazig , Wells Darren M. , Vigouroux Yves , Laplaze Laurent 
Published: February 2023

AbstractSeedling root traits impact plant establishment under challenging environments. Pearl millet is one of the most heat and drought tolerant cereal crops that provides a vital food source across the sub-Saharan Sahel region. Pearl millet’s early root system features a single fast-growing primary root which we hypothesize is an adaptation to the Sahelian climate. Using crop modelling, we demonstrate that early drought stress is an important constraint in agrosystems in the Sahel where pearl millet was domesticated. Furthermore, we show that increased pearl millet primary root growth is correlated with increased early water stress tolerance in field conditions. Genetics including GWAS and QTL approaches identify genomic regions controlling this key root trait. Combining gene expression data, re-sequencing and re-annotation of one of these genomic regions identified a glutaredoxin-encoding genePgGRXC9as the candidate stress resilience root growth regulator. Functional characterization of its closest Arabidopsis homologAtROXY19revealed a novel role for this glutaredoxin (GRX) gene clade in regulating cell elongation. In summary, our study suggests a conserved function for GRX genes in conferring root cell elongation and enhancing resilience of pearl millet to its Sahelian environment.
Identifying and tracking mobile elements in evolving compost communities yields insights into the nanobiome
Authors: van Dijk Bram , Farr Andrew D. , Buffard Pauline , Giersdorf Franz , Meijer Jeroen , Dutilh Bas E. , Rainey Paul B. 
Published: February 2023

AbstractMicrobial evolution is driven by rapid changes in gene content mediated by horizontal gene transfer (HGT). While mobile genetic elements (MGEs) are important drivers of gene flux, the nanobiome – the zoo of Darwinian replicators that depend on microbial hosts – remains poorly characterised. New experimental approaches and analyses are necessary to advance our understanding beyond simple pairwise MGE-host interactions. To detect horizontal transfer, a bioinformatic pipeline (xenoseq) was developed to cross-compare metagenomic samples, which was then applied to metagenomic data from evolving compost communities. These communities were routinely exposed to an “MGE cocktail” derived from allopatric communities. We show that this results in horizontal transfer of a multitude of previously undetected MGEs, including bacteriophages, phage-plasmids, megaplasmids, and even nanobacteria. Sequences that spread from one community to another are shown to disproportionally carry characteristics of phages and insertion-sequences,i.e., traits of canonically parasitic MGEs. We also show that one particularly prolific mobile element - a 313 kb plasmid – correlates substantially with rates of ammonia production, which under nitrogen limitation is likely beneficial. Taken together, our data show that new experimental strategies combined with bioinformatic analyses of metagenomic data stand to provide insight into the drivers of microbial community evolution.
The vitamin B3analogue nicotinamide riboside has only very minor effects on reducing muscle damage inmdxmice
Authors: Stan Tiberiu Loredan , Vijver Davy v.d. , Verhaart Ingrid E.C. , Aartsma-Rus Annemieke 
Published: February 2023

AbstractBACKGROUNDVitamin B3 analogue nicotinamide riboside (NR) has been suggested to have beneficial effects on muscle pathology in a mouse model for Duchenne muscular dystrophy (DMD). In muscle dystrophy, NR is thought to act acts by increasing levels of NAD+, to improve mitochondrial functioning and reduce muscle pathology.OBJECTIVEWe here aimed to validate the effects of NR to improve muscle quality after eight weeks of treatment in two different mouse models for DMD: the commonly used mdx mouse on a C57BL/10 background (BL10mdx) and the more severely affectedmdxmouse on a DBA/2J background (D2-mdx).METHODSTo study in more detail whether NR treatment had an impact on muscle pathology, we assessed the expression levels of several markers for DMD pathology (fibrosis, regeneration and inflammation) in diaphragm.RESULTSOur data showed a trend for increase in NAD+-levels in blood; only in the D2-mdxNR-treated mice the NAD+-levels were slightly increased. These markers were elevated inmdxmodels compared to controls, but not affected by the NR treatment. Histological analysis of muscle tissues indicated a mild treatment effect in D2-mdxmice.CONCLUSIONSBased on our results, testing NR treatment in clinical trials in DMD patients is not warranted.
The influence of parasite load on transcriptional activity and morphology of a cestode and its ant intermediate host
Authors: Sistermans Tom , Hartke Juliane , Stoldt Marah , Libbrecht Romain , Foitzik Susanne 
Published: February 2023

AbstractParasites with complex life cycles are known to induce phenotypic changes in their intermediate hosts to increase transmission to the final host. The magnitude of these changes could increase with the number of parasites, which would be beneficial to co-infecting parasites. Yet, adverse effects of high parasite load (i.e., many parasites in a single host) might stress both hosts and parasites (e.g., through an increased immune response). We investigated the consequences of parasite load on the transcriptional activity and morphology of the cestodeAnomotaenia brevisand its intermediate host, the antTemnothorax nylanderi. We demonstrated that many differentially expressed host genes shifted with parasite load, and their functions indicate a stronger immune response and fight against oxidative stress in heavily infected hosts. The expression of other host genes responded to infection in an all-or-nothing manner, as did the morphology of the host workers. However, the cestodes became smaller when they competed with other parasites for resources from a single host. Their expression profile further indicated shifts in host immune avoidance, starvation resistance and vesicle-mediated transport. In summary, our study reveals clear consequences of parasite load and highlights specific processes and traits affected by this.
Graded functional organisation in the left inferior frontal gyrus: evidence from task-free and task-based functional connectivity
Authors: Diveica Veronica , Riedel Michael C. , Salo Taylor , Laird Angela R. , Jackson Rebecca L. , Binney Richard J. 
Published: February 2023

AbstractThe left inferior frontal gyrus (LIFG) has been ascribed key roles in numerous cognitive domains, including language, executive function and social cognition. However, its functional organisation, and how the specific areas implicated in these cognitive domains relate to each other, is unclear. Possibilities include that the LIFG underpins a domain-general function or, alternatively, that it is characterized by functional differentiation, which might occur in either a discrete or a graded pattern. The aim of the present study was to explore the topographical organisation of the LIFG using a bimodal data-driven approach. To this end, we extracted functional connectivity (FC) gradients from 1) the resting-state fMRI time-series of 150 participants (77 female), and 2) patterns of co-activation derived meta-analytically from task data across a diverse set of cognitive domains. We then sought to characterize the FC differences driving these gradients with seed-based resting-state FC and meta-analytic co-activation modelling analyses. Both analytic approaches converged on an FC profile that shifted in a graded fashion along two main organisational axes. An anterior-posterior gradient shifted from being preferentially associated with high-level control networks (anterior LIFG) to being more tightly coupled with perceptually-driven networks (posterior). A second dorsal-ventral axis was characterized by higher connectivity with domain-general control networks on one hand (dorsal LIFG), and with the semantic network, on the other (ventral). These results provide novel insights into a graded functional organisation of the LIFG underpinning both task-free and task-constrained mental states, and suggest that the LIFG is an interface between distinct large-scale functional networks.Significance statementTo understand how function varies across the LIFG, we conducted a detailed, bimodal exploration of the spatial transitions in its voxel-wise FC patterns. We provide novel evidence of graded changes along two main organisational axes. Specifically, the LIFG was characterized by an anterior-posterior gradient, which could reflect a shift in function from perceptually-driven processing to task-oriented control processes. Moreover, we revealed a dorsal-ventral shift in FC that is consistent with the idea that domain-specificity is a core principle underpinning functional organisation of the LIFG. These gradients were replicated across task-free and task-constrained FC measures, suggesting that a similar fundamental organisation underpins both mental states.
Genetically Defined Subtypes of Somatostatin-Containing Cortical Interneurons
Authors: Hostetler Rachel E. , Hu Hang , Agmon Ariel 
Published: February 2023

ABSTRACTInhibitory interneurons play a crucial role in proper development and function of the mammalian cerebral cortex. Of the different inhibitory subclasses, dendritic-targeting, somatostatin-containing (SOM) interneurons may be the most diverse. Earlier studies used transgenic mouse lines to identify and characterize subtypes of SOM interneurons by morphological, electrophysiological and neurochemical properties. More recently, large-scale studies classified SOM interneurons into 13 morpho-electro-transcriptomic (MET) types. It remains unclear, however, how these various classification schemes relate to each other, and experimental access to MET types has been limited by the scarcity of type-specific mouse driver lines. To begin to address these issues we crossed Flp and Cre driver mouse lines and a dual-color combinatorial reporter, allowing experimental access to genetically defined SOM subsets. Brains from adult mice of both sexes were retrogradely dye-labeled from the pial surface to identify layer 1-projecting neurons, and immunostained against several marker proteins, allowing correlation of genetic label, axonal target and marker protein expression in the same neurons. Using whole-cell recordings ex-vivo, we compared electrophysiological properties between intersectional and transgenic SOM subsets. We identified two layer 1-targeting intersectional subsets with non-overlapping marker protein expression and electrophysiological properties which, together with a previously characterized layer 4-targeting subtype, account for about half of all layer 5 SOM cells and >40% of all SOM cells, and appear to map onto 5 of the 13 MET types. Genetic access to these subtypes will allow researchers to determine their synaptic inputs and outputs and uncover their roles in cortical computations and animal behavior.SIGNIFICANCE STATEMENTInhibitory neurons are critically important for proper development and function of the cerebral cortex. Although a minority population, they are highly diverse, which poses a major challenge to investigating their contributions to cortical computations and animal and human behavior. As a step towards understanding this diversity we crossed genetically modified mouse lines to allow detailed examination of genetically-defined groups of the most diverse inhibitory subtype, somatostatin-containing interneurons. We identified and characterized three somatostatin subtypes in the deep cortical layers with distinct combinations of anatomical, neurochemical and electrophysiological properties. Future studies could now use these genetic tools to examine how these different subtypes are integrated into the cortical circuit and what roles they play during sensory, cognitive or motor behavior.
Sindbis virus is suppressed in the yellow fever mosquitoAedes aegyptiby ATG-6/Beclin-1 mediated activation of autophagy
Authors: Pujhari Sujit , Heu Chan C. , Brustolin Marco , Johnson Rebecca M. , Kim Donghun , Rasgon Jason L. 
Published: February 2023

AbstractAutophagy is a critical modulator of pathogen invasion response in vertebrates and invertebrates. However, how it affects mosquito-borne viral pathogens that significantly burden public health remains underexplored. To address this gap, we use a genetic approach to activate macroautophagy/autophagy in the yellow fever mosquito (Aedes aegypti), infected with a recombinant Sindbis virus (SINV) expressing an autophagy activator. We first demonstrate a 17- amino acid peptide derived from theAe. aegyptiautophagy-related protein 6 (ATG-6/beclin-1-like protein) is sufficient to induce autophagy in C6/36 mosquito cells, as marked by lipidation of ATG- 8 and puncta formation. Next, we engineered a recombinant SINV expressing this bioactive beclin- 1-like peptide and used it to infect and induce autophagy in adult mosquitoes. We find that modulation of autophagy using this recombinant SINV negatively regulated production of infectious viruses. The results from this study improve our understanding of the role of autophagy in arboviruses in invertebrate hosts and also highlight the potential for the autophagy pathway to be exploited for arboviral control.