bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selection, recombination and population history effects on runs of homozygosity (ROH) in wild red deer (Cervus elaphus)
Authors: Hewett Anna M. , Stoffel Martin A. , Peters Lucy , Johnston Susan E. , Pemberton Josephine M. 
Published: January 2023

AbstractThe distribution of runs of homozygosity (ROH) may be shaped by a number of interacting processes such as selection, recombination and population history, but little is known about the importance of these mechanisms in shaping ROH in wild populations. We combined an empirical dataset of >3,000 red deer genotyped at >35,000 genome-wide autosomal SNPs and evolutionary simulations to investigate the influence of each of these factors on ROH. We assessed ROH number and location in two populations of red deer (a focal and comparison) to investigate the effect of population history. We investigated the role of recombination using both a physical map and a genetic linkage map to search for ROH. We found differences in ROH distribution between both populations and both map types indicating that population history and local recombination rate have a substantial effect on ROH. Finally, we ran forward genetic simulations with varying population histories, recombination rates and levels of selection, allowing us to further interpret our empirical data. These simulations showed that population history has a greater effect on ROH distribution than either recombination or selection. We further show that selection can cause genomic regions where ROH are common, so called ROH hotspots, only when the effective population size (Ne) is large or selection is particularly strong. In populations having undergone a population bottleneck, genetic drift can outweigh the effect of selection. We show that most ROH hotspots in the Rum population are in line with expectations from neutral simulations, however two ROH hotspots show possible signatures of selection. Overall, we conclude that in this population, genetic drift resulting from a historical population bottleneck is most likely to have resulted in the observed ROH distribution, with selection possibly playing a minor role.
Transcriptional and Histone acetylation changes associated with CRE elements expose key factors governing the regulatory circuit in early stage of Huntington’s disease models
Authors: Arancibia-Opazo Sandra , Contreras-Riquelme J. Sebastián , Sánchez Mario , Cisternas-Olmedo Marisol , Vidal René L. , Martin Alberto J. M. , Sáez Mauricio A. 
Published: January 2023

AbstractHuntington’s disease (HD) is a disorder caused by an abnormal expansion of trinucleotide CAG repeats within the huntingtin (Htt) gene. Under normal conditions, the CREB Binding Protein interacts with CREB elements and acetylates Lysine 27 of Histone 3 to direct the expression of several genes. However, mutant Htt causes depletion of CBP which in turn induces altered histone acetylation patterns and transcriptional deregulation.Here, we have studied differential expression analysis and H3K27ac variation in 4- and 6-week-old R6/2 mice as a model of juvenile HD. Analysis of differential gene expression and acetylation levels were integrated into Gene Regulatory Networks revealing key regulators involved in the altered transcription cascade.Our results show changes in acetylation and gene expression levels that are related to impaired neuronal development and key regulators clearly defined in 6-week-old mice are proposed to drive the downstream regulatory cascade in HD.Here we describe the first approach to determine the relationship among epigenetic changes in the early stages of HD. We determined the existence of changes in pre-symptomatic stages of HD, a starting point for early onset indicators of the progression of this disease.
The more, the merrier: multivariate phase synchronization methods excel pairwise ones in estimating functional brain connectivity from reconstructed neural sources
Authors: Bruña Ricardo , Cuesta Pablo , Ramírez-Toraño Federico , Suárez-Méndez Isabel , Pereda Ernesto 
Published: January 2023

AbstractThe estimation of functional connectivity (FC) from electro-(EEG) or magnetoencephalographic (MEG) recordings suffers from low spatial resolution, being one of the reasons for the reduced number of sensors compared to the number of reconstructed sources of activity. This problem can be avoided by estimating FC between larger regions instead of individual sources. However, combining all the sources in each area to produce a single time series per region is far from trivial.We have used simultaneous EEG/MEG data from 11 participants and compared the FC estimates from both techniques by using different multivariate approaches. Since the underlying generators are identical for EEG and MEG, the more similar the FC estimation from both techniques is, the more accurate it is likely to be. The results show that using either the average or the root-mean-square of the bivariate source-to-source FC estimates consistently outperforms the use of a representative time series from each area.We concluded that the reconstructed activity in each brain region is too complex to be reduced to a single representative time series and that full multivariate approaches must be used to describe between-area FC from electrophysiological recordings accurately. Moreover, the high correlation between the FC values estimated from EEG and MEG suggests that the results found in the high-sensitivity, low-noise MEG can be transferable to the more affordable EEG, at least when high-quality source reconstruction is used.
Single-cell sequencing for the molecular identity involved in zinc therapy for spinal cord injury
Authors: Shi Zuqiang , Lin Jiaquan , Ge Minghao , Hu Hengshuo , Mao Liang , Tian Miaomiao , Tian He , Mei Xifan 
Published: January 2023

AbstractSpinal cord injury (SCI) is a severe traumatic neurological condition often caused by car accidents, violent impacts, or unintentional falls and can have devastating consequences for the patient. SCI include primary and secondary injuries. Followed by primary injury, and secondary injuries including inflammatory responses and oxidative stress, which exacerbate the disease process of SCI. Therefore, the treatment of SCI, especially the suppression of secondary injuries, is a major focus of attention in the field of neuroscience. In previous studies, we have demonstrated that zinc therapy can exert neuroprotective effects in mice after acute SCI, including reducing the inflammatory response in the central nervous system, decreasing the neuronal apoptosis and downregulating oxidative stress at the region of injury. However, little is known about how zinc therapy systematically alleviates SCI. Here, we have systematically analysed and mapped the single-cell atlas of the spinal cord in mice with SCI treated by zinc therapy, which provides a systematic analysis of the transcriptome of individual cells in the spinal cord. Among the results, we found that zinc therapy-induced alterations in the IL-17 inflammatory pathway and produced immune heterogeneity in microglia which are the inherent immune cells in the central nervous system. By cell subpopulations clustering analysis, we defined seven microglia subpopulations in zinc-therapy spinal cord tissue and identified the presence of novel VEGFA+ microglia. This finding presents that the microglia subpopulations affected by zinc therapy may have the potential to promote angiogenesis, which is a potential mechanism for the treatment of SCI. In conclusion, this study maps/reveals the transcriptomic of zinc therapy for the treatment of acute SCI with unprecedented resolution and provides a molecular basis for the clinical application.
Multiomic interpretation of fungus-infected ant metabolomes during manipulated summit disease
Authors: Will I. , Attardo G. M. , de Bekker C. 
Published: January 2023

AbstractCamponotus floridanusants show altered behaviors followed by a fatal summiting phenotype when infected with manipulatingOphiocordyceps camponoti-floridanifungi. Host summiting as a strategy to increase transmission is also observed with parasite taxa beyond fungi, including aquatic and terrestrial helminths and baculoviruses. The drastic phenotypic changes can sometimes reflect significant physiological changes within host cells that span molecular levels from metabolites to nucleic acids. Nevertheless, the underlying mechanisms still need to be fully characterized. To investigate the small molecules producing summiting behavior, we infectedC. floridanusants withO. camponoti-floridaniand sampled their heads for LC-MS/MS when we observed the characteristic summiting phenotype. We link this metabolomic data with our previous genomic and transcriptomic data to propose mechanisms that underlie manipulated summiting behavior in “zombie ants.” This “multiomic” evidence points toward the dysregulation of neurotransmitter levels and neuronal signaling. We propose that these processes are altered during infection and manipulation based on 1) differential expression of neurotransmitter synthesis and receptor genes, 2) altered abundance of metabolites and neurotransmitters (or their precursors) with known behavioral effects in ants and other insects, and 3) possible suppression of a connected immunity pathway. We additionally report signals for metabolic activity during manipulation related to primary metabolism, detoxification, and anti-stress protectants.
Rapid turnover and evolution of sex-determining regions amongSebastesrockfishes
Authors: Sykes Nathan T.B. , Raj Kolora Sree Rohit , Sudmant Peter H. , Owens Gregory L. 
Published: January 2023

AbstractNature has evolved a wealth of sex determination (SD) mechanisms, driven by both genetic and environmental factors. Recent studies of SD in fishes have shown that not all taxa fit the classic paradigm of sex chromosome evolution and diverse SD methods can be found even among closely related species. Here, we apply a suite of genomic approaches to investigate sex-biased genomic variation in eight species ofSebastesrockfish found in the northeast Pacific Ocean. Using recently assembled chromosome-level rockfish genomes, we leverage published sequence data to identify disparate sex chromosomes and sex-biased loci in five species. We identify two putative male sex chromosomes inS. diaconus, a single putative sex chromosome in the sibling speciesS. carnatusandS. chrysomelas, and an unplaced sex determining contig in the sibling speciesS. miniatusandS. crocotulus. Our study provides evidence for disparate means of sex determination within a recently diverged set of species, and sheds light on the diverse origins of sex determination mechanisms present in the animal kingdom.
Defining the contribution of microRNA-specific slicing Argonautes in animals
Authors: Pal Anisha , Vasudevan Vaishnav , Houle François , Lantin Michael , Maniates Katherine A. , Huberdeau Miguel Quévillon , Abbott Allison L. , Simard Martin J. 
Published: January 2023

ABSTRACTmicroRNAs regulate gene expression through interaction with an Argonaute protein family member. While some members of this protein family retain an enzymatic activity capable of cleaving RNA molecules complementary to Argonaute-bound small RNAs, the role of the slicing activity in the canonical microRNA pathway is still unclear in animals. To address the importance of slicing Argonautes in animals, we createdCaenorhabditis elegansstrains, carrying catalytically dead endogenous ALG-1 and ALG-2, the only two slicing Argonautes essential for the miRNA pathway in this animal model. We observe that the loss of ALG-1 and ALG-2 slicing activity affects overall animal fitness and causes phenotypes, reminiscent of miRNA defects, only when grown and maintained at restrictive temperature. Furthermore, the analysis of global miRNA expression shows that the catalytic activity of ALG-1 and ALG-2 differentially regulate the level of specific subsets of miRNAs in young adults. We also demonstrate that altering the slicing activity of those miRNA-specific Argonautes does not result in any defect in the production of canonical miRNAs. Together, these data support that the slicing activity of miRNA- specific Argonautes function to maintain the levels of a set of miRNAs for optimal viability and fitness in animals particularly exposed to specific growing conditions.
The catalytic activity of microRNA Argonautes plays a modest role in microRNA star strand destabilization inC. elegans
Authors: Kotagama Kasuen , Grimme Acadia L. , Braviner Leah , Yang Bing , Sakhawala Rima M. , Yu Guoyun , Benner Lars Kristian , Joshua-Tor Leemor , McJunkin Katherine 
Published: January 2023

AbstractMany Argonaute proteins can cleave RNA (“slicing”) as part of the microRNA-induced silencing complex (miRISC), even though miRNA-mediated target repression is generally independent of target cleavage. Here we use genome editing inC. elegansto examine the role of miRNA-guided slicing in organismal development. In contrast to previous work, slicing-inactivating mutations did not interfere with normal development when introduced by CRISPR. We find that unwinding and decay of miRNA star strands is weakly defective in the absence of slicing, with the largest effect observed in embryos. Argonaute-Like Gene 2 (ALG-2) is more dependent on slicing for unwinding than ALG-1. The miRNAs that displayed the greatest (albeit minor) dependence on slicing for unwinding tend to form stable duplexes with their star strand, and in some cases, lowering duplex stability alleviates dependence on slicing. Gene expression changes were consistent with negligible to moderate loss of function for miRNA guides whose star strand was upregulated, suggesting a reduced proportion of mature miRISC in slicing mutants. While a few miRNA guide strands are reduced in the mutant background, the basis of this is unclear since changes were not dependent on EBAX-1, a factor in the Target-Directed miRNA Degradation (TDMD) pathway. Overall, this work defines a role for miRNA Argonaute slicing in star strand decay; future work should examine whether this role could have contributed to the selection pressure to conserve catalytic activity of miRNA Argonautes across the metazoan phylogeny.
Wirelessin vivoRecording of Cortical Activity by an Ion-Sensitive Field Effect Transistor
Authors: Bhatt Suyash , Masterson Emily , Zhu Tianxiang , Eizadi Jenna , George Judy , Graupe Nesya , Vareberg Adam , Phillips Jack , Bok Ilhan , Dwyer Matthew , Ashtiani Alireza , Hai Aviad 
Published: January 2023

AbstractWireless brain technologies are empowering basic neuroscience and clinical neurology by offering new platforms that minimize invasiveness and refine possibilities during electrophysiological recording and stimulation. Despite their advantages, most systems require on-board power supply and sizeable transmission circuitry, enforcing a lower bound for miniaturization. Designing new minimalistic architectures that can efficiently sense neurophysiological events will open the door to standalone microscale sensors and minimally invasive delivery of multiple sensors. Here we present a circuit for sensing ionic fluctuations in the brain by an ion-sensitive field effect transistor that detunes a single radiofrequency resonator in parallel. We establish sensitivity of the sensor by electromagnetic analysis and quantify response to ionic fluctuationsin vitro. We validate this new architecturein vivoduring hindpaw stimulation in rodents and verify correlation with local field potential recordings. This new approach can be implemented as an integrated circuit for wirelessin siturecording of brain electrophysiology.
Cortex-wide topography of 1/f-exponent in Parkinson’s disease
Authors: Helson Pascal , Lundqvist Daniel , Svenningsson Per , Vinding Mikkel C. , Kumar Arvind 
Published: January 2023

AbstractParkinson’s Disease causes progressive and debilitating changes to the brain as well as to the mind. While the diagnostic hallmark features are the characteristic movement-related symptoms, the disease also causes decline in sensory processing, cognitive, emotional performance and most patients develop dementia over time. The extent of symptoms and the brain-wide projections of neuromodulators such as dopamine suggest that many brain regions are simultaneously affected in Parkinson’s disease. To characterise such disease-related and brain-wide changes in neuronal function, we performed a source level analysis of resting state magnetoencephalogram (MEG) from two groups: Parkinson’s disease patients and healthy controls. Besides standard spectral analysis, we quantified the aperiodic component of the neural activity by fitting a power law (κ/fλ) to the MEG spectrum and then studied its relationship with age and UPDRS. Consistent with previous results, the most significant spectral changes were observed in the high theta/low alpha band (7-10 Hz) in all brain regions. Furthermore, analysis of the aperiodic part of the spectrum showed that, in all but frontal regions, λ was significantly larger in Parkinson’s disease patients than in control subjects. Our results indicate for the first time that Parkinson’s disease is associated with significant changes in population activity across the whole neocortex. Surprisingly, even early sensory areas showed a significantly larger λ in patients than in healthy controls. Moreover, λ was not affected by the L-dopa medication. Finally, λ was positively correlated with patient age but not with UPDRS-III (summary measure of motor symptoms’ clinical rating). Because λ is closely associated excitationinhibition balance, our results propose new hypotheses about manifestation of Parkinson’s disease in cortical networks.
Absolute quantification of photoreceptor outer segment proteins
Authors: Skiba Nikolai P. , Lewis Tylor R. , Spencer William J. , Castillo Carson M. , Shevchenko Andrej , Arshavsky Vadim Y. 
Published: January 2023

AbstractPhotoreceptor cells generate neuronal signals in response to capturing light. This process, called phototransduction, takes place in a highly specialized outer segment organelle. There are significant discrepancies in the reported amounts of many proteins supporting this process, particularly those of low abundance, which limits our understanding of their molecular organization and function. In this study, we used quantitative mass spectrometry to simultaneously determine the abundances of twenty key structural and functional proteins residing in mouse rod outer segments. We computed the absolute number of molecules of each protein residing within an individual outer segment and the molar ratio amongst all twenty proteins. The molar ratios of proteins comprising three well-characterized constitutive complexes in outer segments differed from the established subunit stoichiometries of these complexes by less than 7%, highlighting the exceptional precision of our quantification. Overall, this study resolves multiple existing discrepancies regarding the outer segment abundances of these proteins, thereby advancing our understanding of how the phototransduction pathway functions as a single, well-coordinated molecular ensemble.
Gene expression of macaques infected with malaria species of zoonotic concern
Authors: Trujillo Amber E. , Bergey Christina M. 
Published: January 2023

ABSTRACTA multitude of malaria species (genusPlasmodium) infects primates. Due to their public health importance, the human-infective species have garnered the most focus, but increased knowledge of non-human primate malaria species is warranted to improve our evolutionary understanding of host-parasite interactions. Additionally, the broad host tropism of some primate malaria parasites and their realized or theorized zoonotic potential add urgency to understanding of primate-parasite interactions. Here, we use comparative transcriptomics to understand the rhesus macaque (Macaca mulatta) response to two malaria parasites used as analogues to human-infective species of differing severity and which may represent emerging zoonotic threats:P. coatneyi, comparable to human-infectiveP. falciparum, andP. cynomolgi, comparable to human-infectiveP. vivax. We first validate our transcriptomics-based proxy of parasite load through comparison to gold-standard microscopy-based measures. We then find that malaria-associated host genes have functional links to immune system regulation and blood cells. Host genes with differing expression by malaria species were more likely to be involved in brain-linked functions, perhaps due to the differential central nervous system involvement of the two parasite species. Such comparative work on primate malaria species may help elucidate the essential and species-specific molecular mechanisms that underlie differing clinical presentations and zoonotic risk.
Interactions between terminal ribosomal RNA helices stabilize theEscherichia colilarge ribosomal subunit
Authors: Nissley Amos J. , Kamal Tammam S. , Cate Jamie H. D. 
Published: January 2023

ABSTRACTThe ribosome is a large ribonucleoprotein assembly that uses diverse and complex molecular interactions to maintain proper folding.In vivoassembled ribosomes have been isolated using MS2-tags installed in either the 16S or 23S ribosomal RNAs (rRNAs), to enable studies of ribosome structure and functionin vitro. RNA tags in theEscherichia coli50S subunit have commonly been inserted into an extended helix H98 in 23S rRNA, as this addition does not affect cellular growth orin vitroribosome activity. Here, we find thatE. coli50S subunits with MS2 tags inserted in H98 are destabilized compared to wild type (WT) 50S subunits. We identify the loss of RNA-RNA tertiary contacts that bridge helices H1, H94, and H98 as the cause of destabilization. Using cryogenic electron microscopy (cryo-EM), we show that this interaction is disrupted by the addition of the MS2 tag and can be restored through the insertion of a single adenosine in the extended H98 helix. This work establishes ways to improve MS2 tags in the 50S subunit that maintain ribosome stability and investigates a complex RNA tertiary structure that may be important for stability in various bacterial ribosomes.
Immune sensing of food allergens promotes aversive behaviour
Authors: Florsheim Esther B. , Bachtel Nathaniel D. , Cullen Jaime , Lima Bruna G. C. , Godazgar Mahdieh , Zhang Cuiling , Carvalho Fernando , Gautier Gregory , Launay Pierre , Wang Andrew , Dietrich Marcelo O. , Medzhitov Ruslan 
Published: January 2023

ABSTRACTIn addition to its canonical function in protecting from pathogens, the immune system can also promote behavioural alterations1–3. The scope and mechanisms of behavioural modifications by the immune system are not yet well understood. Using a mouse food allergy model, here we show that allergic sensitization drives antigen-specific behavioural aversion. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus, and central amygdala. Food aversion requires IgE antibodies and mast cells but precedes the development of gut allergic inflammation. The ability of allergen-specific IgE and mast cells to promote aversion requires leukotrienes and growth and differentiation factor 15 (GDF15). In addition to allergen-induced aversion, we find that lipopolysaccharide-induced inflammation also resulted in IgE-dependent aversive behaviour. These findings thus point to antigen-specific behavioural modifications that likely evolved to promote niche selection to avoid unfavourable environments.