bluuebunny/crossref_metadata_2025_split huggingface dataset:
Theta cycle dynamics of spatial representations in the lateral septum
Authors: Bzymek Katarzyna , Kloosterman Fabian 
Published: July 2023

SummaryAn internal representation of the environment – or map – allows animals to evaluate multiple routes and adapt their navigation strategy to current needs and future goals. The hippocampal formation plays a crucial role in learning a spatial map and using the map for goal-directed navigation. The lateral septum forms a major node for connections between the hippocampus and subcortical brain regions that could link the spatial map to motivation and reward processing centers such as the ventral tegmental area and hypothalamus. It is not known, however, how the lateral septum contributes to the processing of spatial information and route planning.In this study, we investigated the temporal dynamics of spatial representations in the lateral septum. Neuropixels probes were used to record cellular activity along the dorsal-ventral extent of the lateral septum while rats performed one of two spatial navigation tasks in a Y-maze. The activity of a large fraction of cells was theta rhythmic and a subset of cells showed evidence of being active on alternate theta cycles (theta cycle skipping). Both theta rhythmicity and cycle skipping were strongest in the dorsal lateral septum. Similarly, spatially selective firing was most prominent in the dorsal lateral septum. Using neural decoding, we show that the lateral septum cell population encodes both the current location and alternatingly the possible future paths within single theta cycles when rats approach the choice point in the maze.Our data further shows that the alternating expression of spatial representations in the lateral septum is task-dependent, such that it is strongest when the task also requires the animals to alternate between rewarded goal arms. These data suggest that task demands and experience shape which representations are activated near a choice point. The lateral septum receives strong input from hippocampal place cells, and while there may be integration and transformation of incoming spatial signals, our findings support the idea that hippocampal spatial representations and their temporal dynamics are conveyed to subcortical projection areas through the lateral septum.
The ACE-inhibitor drug captopril inhibits ACN-1 to control dauer formation and aging
Authors: Egan Brian M. , Pohl Franziska , Anderson Xavier , Williams Shoshana C. , Adodo Imienreluefe Gregory , Hunt Patrick , Wang Zuoxu , Chiu Chen-Hao , Scharf Andrea , Mosley Matthew , Kumar Sandeep , Schneider Daniel L. , Fujiwara Hideji , Hsu Fong-Fu , Kornfeld Kerry 
Published: July 2023

AbstractThe renin-angiotensin-aldosterone system (RAAS) plays a well-characterized role regulating blood pressure in mammals. Pharmacological and genetic manipulation of the RAAS has been shown to extend lifespan inC. elegans,Drosophila, and rodents, but its mechanism is not well defined. Here we investigate the angiotensin-converting enzyme (ACE) inhibitor drug captopril, which extends lifespan in worms and mice. To investigate the mechanism, we performed a forward genetic screen for captopril hypersensitive mutants. We identified a missense mutation that causes a partial loss-of-function of thedaf-2receptor tyrosine kinase gene, a powerful regulator of aging. The homologous mutation in the human insulin receptor causes Donohue syndrome, establishing these mutant worms as an invertebrate model of this disease. Captopril functions inC. elegansby inhibiting ACN-1, the worm homolog of ACE. Reducing the activity ofacn-1via captopril or RNAi promoted dauer larvae formation, suggestingacn-1is adafgene. Captopril-mediated lifespan extension xwas abrogated bydaf-16(lf)anddaf-12(lf)mutations. Our results indicate that captopril andacn-1control aging by modulating dauer formation pathways. We speculate that this represents a conserved mechanism of lifespan control.Summary StatementCaptopril andacn-1control aging. By demonstrating they regulate dauer formation and interact withdafgenes, including a new DAF-2(A261V) mutant corresponding to a human disease variant, we clarified the mechanism.
Updated Biomarkers for TNBC in African vs. Caucasian American Women
Authors: Croft Jacob , Quintanar Odalys , Zhang Jun 
Published: July 2023

AbstractIntroductionBreast cancer, especially triple-negative breast cancer (TNBC), is a significant concern in the US, being the most common cancer among women and the second leading cause of cancer-related deaths. TNBC lacks crucial receptors targeted in other breast cancer types, leading to a poor prognosis and limited treatment options due to its aggressive and heterogeneous nature.SignificanceAfrican American women (AAW) with TNBC face higher mortality rates and more aggressive disease compared to Caucasian American women (CAW). Despite efforts to find biomarkers specific to AAW and CAW with TNBC, limited sample availability and data resources have been obstacles.MethodsIn our study, we examined 237 candidate peptide biomarkers using publicly available data.Resultsidentify 23 unique prognostic biomarkers. These biomarkers accurately assess patient conditions based on race-specific gene expression patterns, holding potential to address racial disparities in TNBC treatment.ConclusionOverall, our research sheds light on how racial genetic profiles influence TNBC prognosis and treatment efficacy. The identified prognostic biomarkers pave the way for future studies addressing TNBC racial disparities and personalized treatment approaches.
Positive and negative feedback regulation of the TGF-β1–SMAD4 axis explains two equilibrium states in human skin aging
Authors: Haga Masatoshi , Iida Keita , Okada Mariko 
Published: July 2023

SummarySkin homeostasis during aging is critical not only for the appearance but also biological defense of the human body. In this study, we identified thrombospondin-1 (THBS1) and fibromodulin (FMOD) as positive and negative regulators, respectively, of the TGF-β1–SMAD4 axis in human skin aging based onin vitroandin vivoomics analyses and mathematical modeling. Transcriptomic and epigenetic analyses of senescent dermal fibroblasts identified TGF-β1 as the key upstream regulator. Bifurcation analysis identified a binary senescent/non-senescent switch, with THBS1 as the main controller. Sensitivity analysis of the TGF-β1 signaling pathway indicated that THBS1 expression was sensitively regulated while FMOD was robustly regulated, suggesting that THBS1 is a controllable factor. Inhibition of SMAD4 complex formation was experimentally validated as a promising manner to control THBS1 production and senescence. This study demonstrates the potential of a data-driven mathematical approach in determining the mechanisms of skin aging.Graphical abstracteTOC BlurbHaga, Iida and Okada revealed that the balance between FMOD and THBS1 determines the two equilibrium states of skin homeostasis and THBS1 is a controllable factor in skin agingHighlightsMulti-omics analysis identified TGF-β1–SMAD4 as key regulators in human skin agingTHBS1 and FMOD promoted and suppressed factors in skin aging, respectivelyTHBS1 controlled the senescent and non-senescent states of the aging switchSMAD4 is a potential target for inhibiting THBS1 expression and cell senescence
Alternative splicing and its regulation in the malaria vectorAnopheles gambiae
Authors: Díaz-Terenti Bárbara , Gómez-Díaz Elena 
Published: July 2023

AbstractAlternative splicing (AS) is a highly conserved mechanism that allows to expand the coding capacity of the genome, by modifying how multiple isoforms are expressed or used to generate different phenotypes. Despite its importance in physiology and disease, genome-wide studies of AS are lacking in most insects, including mosquitoes. Even for model organisms, chromatin associated processes involved in the regulation AS are poorly known. In this study, we investigated AS in the mosquitoAnopheles gambiaein the context of tissue-specific gene expression and mosquito responses to aPlasmodium falciparuminfection, as well as the relationship between patterns of differential isoform expression and usage with chromatin accessibility changes. For this, we combined RNA-seq and ATAC-seq data fromA. gambiaemidguts and salivary glands, and from infected and non-infected midguts. We report differences between tissues in the expression of 456 isoforms and in the use of 211 isoforms. Secondly, we find a clear and significant association between chromatin accessibility states and tissue-specific patterns of AS. The analysis of differential accessible regions located at splicing sites permitted the identification of several motifs resembling the binding sites ofDrosophilatranscription factors. Finally, the genome-wide analysis of tissue-dependent enhancer activity revealed that approximately 20% ofA. gambiaetranscriptional enhancers annotate to a differentially expressed or used isoform and that their activation status is linked to AS differences between tissues. This research illuminates the role of AS in gene expression in vector mosquitoes, and identifies regulatory regions potentially involved in AS regulation, which could reveal novel strategies for vector control.
Reference genome for the Northern bat (Eptesicus nilssonii), a most northern bat species
Authors: Laine Veronika N. , Pulliainen Arto T. , Lilley Thomas M. 
Published: July 2023

AbstractThe northern bat (Eptesicus nilssonii) is the most northern bat species in the world. Its distribution covers whole Eurasia, and the species is thus well adapted to different habitat types. However, recent population declines have been reported and rapid conservation efforts are needed. Here we present a high-qualityde novogenome assembly of a female northern bat from Finland (BLF_Eptnil_asm_v1.0). The assembly was generated using a combination of Pacbio and Omni-C technologies. The primary assembly comprises 726 scaffolds spanning 2.0 Gb, represented by a scaffold N50 of 102 Mb, a contig N50 of 66.2 Mb, and a BUSCO completeness score of 93.73%. Annotation of the assembly identified 20,250 genes. This genome will be an important resource for the conservation and evolutionary genomic studies especially in understanding how rapid environmental changes affect northern species.
Multi-level processing of emotions in life motion signals revealed through pupil responses
Authors: Yuan Tian , Wang Li , Jiang Yi 
Published: July 2023

AbstractPerceiving emotions from the movements of other biological entities is critical for human survival and interpersonal interactions. Here, we report that emotional information conveyed by point-light biological motion (BM) triggered automatic physiological responses as reflected in pupil size. Specifically, happy BM evoked larger pupil size than neutral and sad BM, while sad BM induced a smaller pupil response than neutral BM. Moreover, this happy over sad pupil dilation effect is negatively correlated with individual autistic traits. Notably, emotional BM with only local motion features retained could also exert modulations on pupils. Compared with intact BM, both happy and sad local BM evoked stronger pupil responses than neutral local BM starting from an earlier timepoint, with no difference between the happy and sad conditions. These results revealed a fine-grained pupil-related emotional modulation induced by intact BM and a coarse but rapid modulation by local BM, demonstrating multi-level processing of emotions in life motion signals. Taken together, our findings shed new light on BM emotion processing, and highlight the potential of utilizing the emotion-modulated pupil response to facilitate the diagnosis of social cognitive disorders.
Beyond Traditional Methods: Innovative Integration of LISS IV and Sentinel 2A Imagery for Unparalleled Insight into Himalayan Ibex Habitat Suitability
Authors: Dutta Ritam , Joshi Bheem Dutt , Kumar Vineet , Sharief Amira , Bhattcharjee Saurav , Babu Rajappa , Thakur Mukesh , Sharma Lalit Kumar 
Published: July 2023

AbstractDespite advancements in remote sensing, satellite imagery is underutilized in conservation research. Multispectral data from various sensors have great potential for mapping landscapes, but distinct spectral and spatial resolution capabilities are crucial for accurately classifying wildlife habitats. Our study aimed to develop a technique for precisely discerning habitat categories for the Himalayan Ibex (Capra sibirica) using different satellite imagery. To address both spectral and spatial challenges, we utilized LISS IV and Sentinel 2A data and integrated the LISS IV data with Sentinel 2A data along with their corresponding geometric information. Employing multiple supervised classification algorithms, we found the Random Forest (RF) algorithm to outperform others. The integrated (LISS IV-Sentinel 2A) classified image achieved the highest accuracy, with an overall accuracy of 86.17% and a Kappa coefficient of 0.84.To map the suitable habitat of the Ibex, we conducted ensemble modeling using the Land Cover Land Use (LCLU) of all three image types (LISS IV, Sentinel 2A, Integrated) and other predictors such as topographical, soil type, vegetation, and water radiometric indices. The integrated model provided the most accurate prediction of suitable habitat for the Ibex, surpassing the other two LCLU classes derived from individual images. The Soil Adjusted Vegetation Index (SAVI) and elevation were identified as crucial factors in identifying suitable habitatsThese findings hold valuable implications for the development of effective conservation strategies, as accurate classification schemes enable the identification of vital landscape elements. By precisely classifying LULC satellite images and identifying crucial habitats for the Ibex, this pilot study provides a new and valuable strategy for conservation planning. It enhances our ability to preserve and protect the habitat of wildlife species in the mountain ecosystem of the Himalayas.
Transcriptional regulation of Dyskerinviacanonical WNT signaling modulates sphingolipid biosynthesis and drives colorectal cancer
Authors: Nigam Shivansh , Khan Umar K. , Praveen Ayush , Shendre Akshay , Carskadon Shannon , Kapoor Abhimanyu , Tiwari Anjali , Chandra Abhijit , Palanisamy Nallasivam , Ateeq Bushra 
Published: July 2023

AbstractTargeting EGFR has been effective in RAS/RAF wild-type colorectal cancer (CRC) patients. However, residual tumor relapses, necessitating the importance of biomarker-guided novel therapeutics. We show elevated DKC1 in ∼88% of CRC patients with poor recurrence-free survival. Clinically,DKC1-positive patients exhibit similarity with CMS2 class, the canonical subtype with active WNT signaling. We show functional significance of DKC1 in cell proliferation, stemness, DNA repair, and survival. Further, mice bearingDKC1knockdown xenografts show ∼81% reduction in tumor burden. Mechanistically, WNT/β-catenin signaling orchestratesDKC1expression, then, DKC1/SOX2 complex regulatesSGPP2, modulating sphingolipids metabolism. Downregulation of DKC1 in CRC lead to reduced SGPP2 levels leading to dysregulation of sphingolipid biosynthesis. Of note,DKC1-high CRC patients show accumulation of ceramides, namely C23 and C24, signifying their utility in diagnosis. Collectively, we delineate the mechanistic circuitry involved in DKC1-mediated CRC progression, propose ceramides as biomarker, and underscore WNT-based therapeutics for DKC1-positive patients.
A Polygenic Quincunx
Authors: Stern Ralph H. 
Published: July 2023

AbstractSequential addition of SNPs (single nucleotide polymorphism) to a risk model repeatedly splits risk groups in two, generating a branching tree. As SNPs are independent, the path of an individual through the tree is a form of random walk. This resembles the path of a ball through a Galton quincunx, but the rules for a polygenic quincunx are more complex. The result is that individuals zigzag to higher and lower risks with each additional SNP. Patient flows through a polygenic quincunx for a few SNPs that aggregate these individual random walks is presented. Longer random walks calculated from Monte-Carlo simulations illustrate how different the individual random walks can be. As random walks do not have unique termini, polygenic risk values don’t converge on unique individual risk estimates. However, the more steps in a random walk, the greater the dispersion of the termini around the starting point. So more SNPs can result in more disperse population polygenic risk distributions, and potentially greater clinical benefit when allocating preventive measures based on risk level.
Profiling the Expression of Transportome Genes in cancer: A systematic approach
Authors: Visentin Luca , Scarpellino Giorgia , Munaron Luca , Ruffinatti Federico Alessandro 
Published: July 2023

AbstractThe transportome, the-omiclayer encompassing all Ion Channels and Transporters (ICTs), is crucial for cell physiology. It is therefore reasonable to hypothesize a role of the transportome in disease, and in particular in cancer. Here, we present the Membrane Transport Protein DataBase (MTP-DB), a database collecting information on ICTs, and a pipeline that takes expression data and the MTP-DB as input to produce a broad overview of transportome dysregulation in cancer. The MTP-DB may prove useful for the study of the transportome in general, and the pipeline may be used to study the transportome in other diseases. Both tools are open source and can be found on GitHub at TCP-Lab/mtp-db and TCP-Lab/transportome_profiler, under permissive licenses. We detect that the transportome is dysregulated in cancer, and that dysregulation patterns are shared among different cancer types. It is still unclear how these patterns are linked to cancer patho-physiology.
Distractor suppression does and does not depend on pre-distractor alpha-band activity
Authors: Redding Zach V. , Fiebelkorn Ian C. 
Published: July 2023

AbstractSelective attention enhances behaviorally important information and suppresses distracting information. Research on the neural basis of selective attention has largely focused on sensory enhancement, with less focus on sensory suppression. Enhancement and suppression can operate through a push-pull relationship that arises from competitive interactions among neural populations. There has been considerable debate, however, regarding (i) whether suppression can also operate independent of enhancement and (ii) whether neural processes associated with the voluntary deployment of suppression can occur prior to distractor onset. We provide further behavioral and electrophysiological evidence of independent suppression at cued distractor locations while humans performed a visual search task. We specifically utilize two established EEG markers of suppression: alpha power (∼8–15 Hz) and the distractor positivity (PD). Increased alpha power has been linked with attenuated sensory processing, while the PD—a component of event-related potentials—has been linked with successful distractor suppression. The present results demonstrate that cueing the location of an upcoming distractor speeded responding and led to an earlier onset PD, consistent with earlier suppression due to strategic use of a spatial cue. We further demonstrate that higher pre-distractor alpha power contralateral to distractors was generally associated with successful suppression on both cued and non-cued trials. However, there was no consistent change in alpha power associated with the spatial cue, meaning cueing effects on behavioral and neural measures occurred independent of alpha-related gating of sensory processing. These findings reveal the importance of pre-distractor neural processes for subsequent distractor suppression.Significance StatementSelective suppression of distracting information is important for survival, contributing to preferential processing of behaviorally important information. Does foreknowledge of an upcoming distractor’s location help with suppression? Here, we recorded EEG while subjects performed a target detection task with cues that indicated the location of upcoming distractors. Behavioral and electrophysiological results revealed that foreknowledge of a distractor’s location speeded suppression, thereby facilitating target detection. The results further revealed a significant relationship between pre-stimulus alpha-band activity and successful suppression; however, pre-stimulus alpha-band activity was not consistently lateralized relative to the spatially informative cues. The present findings therefore demonstrate that target detection can benefit from foreknowledge of distractor location in a process that is independent of alpha-related gating of sensory processing.
The role of serotonin in modulating social competence in a cooperatively breeding fish
Authors: Antunes Diogo F. , Stettler Pia R. , Taborsky Barbara 
Published: July 2023

1.AbstractBehavioural interactions between conspecifics rely on the appreciation of social cues, which is achieved through biochemical switching of pre-existing neurophysiological pathways. Serotonin is one of the major neurotransmitters in the central nervous system responsible for the modulation of physiological and behavioural traits, in particular social behaviour. The importance of serotonin for the ability to optimise ones social behaviour depending on available social information, that is, social competence, is yet unknown. Here we investigate how serotonin and the serotonin 1A receptor (5-HT1A) modulate social competence in a competitive context. In the cooperatively breeding cichlidNeolamprologus pulcher, we pharmacologically manipulated the serotonin availability and 5-HT1Aactivity to test their effects on social behaviours during an asymmetric contest between the owner of a defended territory containing shelter and an intruder devoid of a territory. In this contest, the adequate response by the intruders, the focal individuals in our study, is to show submissive behaviour in order to avoid eviction from the vicinity of the shelter. While the serotonin enhancer Fluoxetine did not affect the frequency of submission towards territory owners, reducing serotonin by a low dosage of 4-Chloro-DL-phenylalanine (PCPA) increased submissive behaviour. Furthermore, threat displays towards territory owners were reduced at high dosages of Fluoxetine and also at the lowest dosage of PCPA. 5-HT1Aactivation increased threat displays by intruders, indicating that this receptor may not be involved in regulating social competence. We conclude that serotonin, but not its receptor 5-HT1Aplays an important role in the regulation of social competence.