bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detect+Track: Robust and flexible software tools for improved tracking and behavioural analysis of fish
Authors: Dutta Abhishek , Pérez-Campanero Natalia , Taylor Graham K. , Zisserman Andrew , Newport Cait 
Published: April 2023

AbstractDevelopments in automated animal behavioural analysis software are increasing the efficiency of data collection and improving the standardization of behavioural measurements. There are now several open-source tools for tracking laboratory animals, but often these are only accurate under limited conditions (e.g. uniform lighting and background, uncluttered scenes, unobstructed focal animal). Tracking fish presents a particular challenge for these tools because movement at the water’s surface introduces significant noise. Partial occlusion of the focal animal can also be troublesome, particularly when tracking the whole organism. But identifying the position of an animal is only part of the task – analysing the movement of the animal relative to their environment and experimental context is often what provides information about their behaviour. Therefore, the automated detection of physical objects and boundaries would also be beneficial, but this feature is not commonly incorporated into existing tracking software. Here we describe a video processing method that uses a range of computer vision algorithms (e.g. object detector and tracker, optical flow, parallel plane homology) and computational geometry techniques (e.g. Voronoi tessellation) to analyse the movement behaviour of fish in response to experimental stimuli. A behavioural experiment, which involved tracking a fish’s trajectory through a field of obstacles, motivated our development of a set of tools that: (1) measure an animal’s trajectory, (2) record obstacle position, and (3) detect when the fish passed through ‘virtual gates’ between adjacent obstacles and/or the aquarium wall. We have introduced a novel Detect+Track approach that significantly enhances the accuracy and robustness of animal tracking, overcoming some of the limitations of existing tools and providing a more reliable solution for complex experimental conditions. Our workflow is divided into several discrete steps, and provides a set of modular software building blocks that can be adapted to analyse other experimental designs. A detailed tutorial is provided, together with all the data and code required to reproduce our results.
Cell-cycle regulator Whi5 shapes proliferative heterogeneity in clonal populations
Authors: Delgado-Román Irene , García-Marcelo María José , Delgado-Ramos Lidia , Chávez Sebastián , Muñoz-Centeno Mari Cruz 
Published: April 2023

AbstractClonal populations exhibit phenotypic variation in spite of being composed of genetically identical cells under equal environmental conditions. Proliferation rate also shows this heterogeneity, but the mechanisms underlying are still poorly understood. Cell cycle regulation controls proliferative capacity and previous transcriptomic studies revealed that budding yeast microcolonies with low proliferation rates display high levels of the G1-S transition inhibitor Whi5. In this work, we combined single cell microencapsulation with confocal microscopy to study heterogeneity in clonal cultures. We found that most slow-growing microcolonies are founded by young mother cells with a very short number of cell division cycles. This reduction in proliferation capacity is related to the expression levels of Whi5, which increases with the number of mother cell replication rounds since early stages. Our results establish that the proliferative structure of a cell population is cumulatively shaped in every mitotic cycle from the very first division, when a mother cell has the opportunity to increase Whi5 expression levels and to develop a slow proliferating lineage.
Host use preference of fruit flies (Diptera: Tephritidae) among selected cucurbitaceous vegetables in Morogoro, Eastern-Central Tanzania
Authors: Tarimo Petronila , Kabota Sija , Mwatawala Maulid , Majubwa Ramadhan , Kudra Abdul , Virgilio Massimiliano , Jordaens Kurt , De Meyer Marc 
Published: April 2023

AbstractFruit flies (Diptera, Tephritidae) represent a major threat to cucurbit production in Tanzania. They cause huge economic losses on cucurbit crops. Information on the infestation and yield loss caused by fruit flies on cucurbit crops is vital in designing a sound fruit fly management program. We identified the fruit fly species attacking cucurbit crops (Cucurbitales: Cucurbitaceae): cucumber (Cucumis sativusL.), watermelon (Citrullus lanatus[Thunb.] Matsum. & Nakai) and squash (Cucurbita moschataD.) in the Morogoro region and quantified their incidence and infestation per crop species. A weekly sampling of ten fruits per crop was repeated twice per plot for each zone for five consecutive weeks between March and October 2020. The number of fruit flies emerging from the collected fruits was quantified and infestation per crop species was determined. We observed significant differences in infestation between cucurbit species, across zones and seasons. Squash showed the highest infestation ofZeugodacus cucurbitae(Coquillet) in both zones followed by watermelon. Watermelon was highly infested byDacus vertebratus(Bigot) in the plateau zone followed by squash. Squash showed the highest infestation ofDacus ciliatusLoew in the plateau zone followed by watermelon. Cucumber had the lowest infestation for all fruit fly species.
DNA-m6A calling and integrated long-read epigenetic and genetic analysis with fibertools
Authors: Jha Anupama , Bohaczuk Stephanie C. , Mao Yizi , Ranchalis Jane , Mallory Benjamin J. , Min Alan T. , Hamm Morgan O. , Swanson Elliott , Dubocanin Danilo , Finkbeiner Connor , Li Tony , Whittington Dale , Noble William Stafford , Stergachis Andrew B. , Vollger Mitchell R. 
Published: April 2023

AbstractLong-read DNA sequencing has recently emerged as a powerful tool for studying both genetic and epigenetic architectures at single-molecule and single-nucleotide resolution. Long-read epigenetic studies encompass both the direct identification of native cytosine methylation as well as the identification of exogenously placed DNAN6-methyladenine (DNA-m6A). However, detecting DNA-m6A modifications using single-molecule sequencing, as well as co-processing single-molecule genetic and epigenetic architectures, is limited by computational demands and a lack of supporting tools. Here, we introducefibertools, a state-of-the-art toolkit that features a semi-supervised convolutional neural network for fast and accurate identification of m6A-marked bases using PacBio single-molecule long-read sequencing, as well as the co-processing of long-read genetic and epigenetic data produced using either PacBio or Oxford Nanopore sequencing platforms. We demonstrate accurate DNA-m6A identification (>90% precision and recall) along >20 kilobase long DNA molecules with a ∼1,000-fold improvement in speed. In addition, we demonstrate thatfibertoolscan readily integrate genetic and epigenetic data at single-molecule resolution, including the seamless conversion between molecular and reference coordinate systems, allowing for accurate genetic and epigenetic analyses of long-read data within structurally and somatically variable genomic regions.
Conservation of dichromatin organization along regional centromeres
Authors: Dubocanin Danilo , Hartley Gabrielle A. , Cortes Adriana E. Sedeno , Mao Yizi , Hedouin Sabrine , Ranchalis Jane , Agarwal Aman , Logsdon Glennis A. , Munson Katherine M. , Real Taylor , Mallory Benjamin J. , Eichler Evan E. , Biggins Sue , O’Neill Rachel J. , Stergachis Andrew B. 
Published: April 2023

SummaryThe focal attachment of the kinetochore to the centromere is essential for genome maintenance, yet the highly repetitive nature of satellite regional centromeres, such as those in humans, limits our understanding of their chromatin organization. We demonstrate that single-molecule chromatin fiber sequencing (Fiber-seq) can uniquely co-resolve kinetochore and surrounding chromatin architectures along point centromeres, revealing largely homogeneous single-molecule kinetochore occupancy along each chromosome. In contrast, extension of Fiber-seq to regional satellite centromeres exposed marked per-molecule heterogeneity in their chromatin organization. Regional CENP-A-marked centromere cores uniquely contain a dichotomous chromatin organization (dichromatin) composed of compacted nucleosome arrays punctuated with highly accessible chromatin patches. CENP-B occupancy phases dichromatin to the underlying alpha-satellite repeat within centromere cores, but is not necessary for dichromatin formation. Centromere core dichromatin is a conserved feature between humans despite the marked divergence of their underlying alpha-satellite organization and is similarly a conserved feature along regional centromeres that lack satellite repeats in gibbon. Overall, the chromatin organization of regional centromeres is defined by marked per-molecule heterogeneity, likely buffering kinetochore attachment against sequence and structural variability within regional centromeres.HighlightsDichotomous accessible and compacted chromatin (dichromatin) marks centromere coresHighly accessible chromatin patches punctuate sites of kinetochore attachmentDichromatin can form irrespective of CENP-B occupancyConservation within centromeres is mediated at the level of chromatin, not DNA
A mouse model for environmentally induced and reversible circadian arrhythmia using gradual exposure to a fragmented day-night cycle
Authors: Richardson Melissa E. S. , Browne Chérie-Akilah , Huerta Mazariegos Citlali I. 
Published: April 2023

AbstractArrhythmia is considered the most disrupted state of the biological circadian clock, and usually occurs when circadian regulatory genes are rendered non-functional, or the master clock (Suprachiasmatic Nucleus) is ablated. Since clock gene expression is aligned by the external solar day-night cycle to exhibit a 24-hour rhythm, we hypothesized that ill-timed light and dark exposure could negatively impact endogenous circadian clock function in mice. In this study, we present an environmentally driven approach to induce arrhythmia in mice that is also reversible. Using the previously characterized fragmented day-night cycle (FDN) where the 8-hour night is split into four 2-hour fragments and equally distributed across the 24-hour day, we show that mice gradually exposed to the FDN for 1 month lose their circadian rhythmicity. Furthermore, subsequent exposure to constant light or constant dark conditions does not yield typical circadian rhythms, but instead, reveals circadian arrhythmia. Finally, we show that the arrhythmic locomotion phenotype is reversible with one week of reintroduction to a 12 hr day-12 hr night cycle. This is the first study to show how the light-dark environment induces arrhythmia of an intact circadian clock and how it can be reversed.
Tailored chemical reactivity probes for systemic imaging of aldehydes in fibroproliferative diseases
Authors: Ma Hua , Zhou Iris Y. , Chen Y. Iris , Rotile Nicholas J. , Ay Ilknur , Akam Eman , Wang Huan , Knipe Rachel , Hariri Lida P. , Zhang Caiyuan , Drummond Matthew , Pantazopoulos Pamela , Moon Brianna F. , Boice Avery T. , Zygmont Samantha E. , Weigand-Whittier Jonah , Sojoodi Mozhdeh , Gonzalez-Villalobos Romer A. , Hansen Michael K. , Tanabe Kenneth K. , Caravan Peter 
Published: April 2023

AbstractDuring fibroproliferation, protein-associated extracellular aldehydes are formed by the oxidation of lysine residues on extracellular matrix proteins to form the aldehyde allysine. Here we report three Mn(II)-based, small molecule magnetic resonance (MR) probes that contain α-effect nucleophiles to target allysine in vivo and report on tissue fibrogenesis. We used a rational design approach to develop turn-on probes with a 4-fold increase in relaxivity upon targeting. The effects of aldehyde condensation rate and hydrolysis kinetics on the performance of the probes to detect tissue fibrogenesis noninvasively in mouse models were evaluated by a systemic aldehyde tracking approach. We showed that for highly reversible ligations, off-rate was a stronger predictor of in vivo efficiency, enabling histologically validated, three-dimensional characterization of pulmonary fibrogenesis throughout the entire lung. The exclusive renal elimination of these probes allowed for rapid imaging of liver fibrosis. Reducing the hydrolysis rate by forming an oxime bond with allysine enabled delayed phase imaging of kidney fibrogenesis. The imaging efficacy of these probes, coupled with their rapid and complete elimination from the body, make them strong candidates for clinical translation.
HB21/40/53 promote inflorescence arrest through ABA accumulation at the end of flowering
Authors: Sánchez-Gerschon Verónica , Ferrándiz Cristina , Balanzà Vicente 
Published: April 2023

AbstractFlowers are produced by the activity of the inflorescence meristem after the floral transition. In plants with indeterminate inflorescences, as Arabidopsis, the final number of flowers produced by the inflorescence meristem will depend on two main factors, the rate of flower production by the meristem and the duration of the phase of inflorescence meristem activity. The end of flowering, understood as the moment when the inflorescence stops the production of new flowers, is associated with the meristem proliferative arrest. At this time point, the meristem ceases to initiate new floral primordia and the unpollinated flowers already formed arrest their development.It has been known for a long time that fruit/seed production induces inflorescence meristem arrest, but the mechanisms controlling this process were elusive. During the last years, the regulation of the end of flowering has started to be elucidated in Arabidopsis. The meristem arrest at the end of flowering is controlled at the genetic level by the FRUITFULL-APETALA2 (FUL-AP2) pathway, that modulates meristem activity. The meristem arrest has been also shown to be controlled at the hormonal level. It has been proposed that auxin could mediate the fruit/seed effect to the meristem. Cytokinins regulation and response have been also proposed as important factors controlling the meristem activity at the end of flowering. Finally, it has been also described that arrested meristems at the end of flowering resembles dormant meristem at the transcriptomic level.Previously, we have shown that the FUL-AP2 pathway controls the expression of the homeodomain leucine zipper transcription factorHOMEOBOX PROTEIN 21(HB21), a gene involved in the establishment of bud axillary dormancy. In this work we characterize the role ofHB21in the control of the proliferative arrest associated with the end of flowering. We observed thatHB21, together withHB40andHB53, accumulate in the inflorescence apexes at the end of flowering promoting the cessation of inflorescence meristem activity. We also show thatHB21induction of in young apexes is sufficient to induce flower and meristem arrest, likely mediated by an increase in ABA responses. Thus, our work confirms the parallelism proposed between dormant meristems and the arrested meristem at the end of flowering, which appear to be regulated by common pathways, and propose ABA as a new regulator in the control of inflorescence meristem arrest.
An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing
Authors: Li Zhongxiao , Zhang Bin , Chan Jia Jia , Tabatabaeian Hossein , Tong Qing Yun , Chew Xiao Hong , Fan Xiaonan , Driguez Patrick , Chan Charlene , Cheong Faith , Wang Shi , Siew Bei En , Tan Ian Jse-Wei , Lee Kai-Yin , Lieske Bettina , Cheong Wai-Kit , Kappei Dennis , Tan Ker-Kan , Gao Xin , Tay Yvonne 
Published: April 2023

AbstractColorectal cancer (CRC) is the second leading cause of cancer death worldwide. In recent years, short-read single-cell RNA sequencing (scRNA-seq) has been instrumental in deciphering tumor cell heterogeneities. However, these studies only enable gene-level expression quantification but neglect alterations in transcript structures, which arise from alternative end processing or splicing, and are frequently observed in cancer. In this study, we integrated short- and long-read scRNA-seq of CRC patient samples to build the first isoform-resolution CRC transcriptomic atlas. We identified 394 dysregulated transcript structures in tumor epithelial cells, including 299 resulting from various combinations of multiple splicing events. Secondly, we characterized genes and isoforms associated with epithelial lineages and subpopulations that exhibit distinct prognoses. Finally, we built an algorithm that integrated novel peptides derived from predicted ORFs of recurrent tumor-specific transcripts with mass spectrometry data and identified a panel of recurring neoepitopes that may aid the development of neoantigen-based cancer vaccines.
Metabolic predictors of response to immune checkpoint blockade therapy
Authors: Shorer Ofir , Yizhak Keren 
Published: April 2023

AbstractMetabolism of immune cells in the tumor microenvironment (TME) plays a critical role in cancer patient response to immune checkpoint inhibitors (ICI). Yet, a metabolic characterization of immune cells in the TME of patients treated with ICI is lacking. To bridge this gap we performed a semi-supervised analysis of ∼1700 metabolic genes using single-cell RNA-seq data of >1 million immune cells from ∼230 tumor and blood samples treated with ICI. When clustering cells based on their metabolic gene expression, we found that similar immunological states are found in different metabolic states. Most importantly, we found metabolic states that are significantly associated with patient response. We then built a metabolic predictor based on a dozen gene signature which significantly differentiates between responding and non-responding patients across different cancer types (AUC = 0.8-0.86). Taken together, our results demonstrate the importance of metabolism in predicting patient response to ICI.
Mammary microvessels are sensitive to menstrual cycle sex hormones
Authors: Moccia Carmen , Cherubini Marta , Fortea Marina , Akinbote Akinola , Padmanaban Prasanna , Sastre Violeta Beltran , Haase Kristina 
Published: April 2023

AbstractThe mammary gland is a highly vascularized organ that is influenced by sex hormones including estrogen (E2) and progesterone (P4). Beyond whole-organism studies in rodents or 2D monocultures, hormonal interactions and their effects on the breast microvasculature remains largely understudied. Recent methods to generate 3D microvessels on-chip have enabled direct observation of complex vascular processes; however, these models often use non-tissue-specific cell types, such as HUVEC and fibroblasts from various sources. Here, novel mammary-specific microvessels are generated by co-culturing primary breast endothelial cells and fibroblasts under optimized culture conditions. These microvessels are mechano-sensitive (to interstitial flow) and require endothelial-stromal interactions to develop fully perfusable vessels. These mammary-specific microvessels are also responsive to exogenous stimulation by sex hormones. When treated with combined E2 and P4, corresponding to the four phases of the menstrual cycle (period, follicular, ovular, and luteal), vascular remodeling and barrier function are altered in a phase-dependent manner. The presence of high E2 (ovulation) promotes vascular growth and remodeling, corresponding to high depletion of proangiogenic factors, whereas high P4 concentrations (luteal) promote vascular regression. The effects of combined E2 and P4 hormones are not only dose-dependent but also tissue-specific, as is shown by similarly treating non-tissue-specific HUVEC microvessels.
Cues for predictive eye movements in naturalistic scenes
Authors: Goettker Alexander , Borgerding Nils , Leeske Linus , Gegenfurtner Karl R. 
Published: April 2023

AbstractWe previously compared following of the same trajectories with eye movements, but either as an isolated target or embedded in a naturalistic scene, in this case the movement of a puck in an ice hockey game. We observed that the oculomotor system was able to leverage the contextual cues available in the naturalistic scene to produce predictive eye movements. In this study we wanted to assess which factors are critical for achieving this predictive advantage by manipulating four factors: the expertise of the viewers, the amount of available peripheral information, and contextual and kinematic cues. The more peripheral information became available (by manipulating the area of the video that was visible), the better the predictions of all observers. However, expert ice hockey fans were consistently more accurate and better at predicting than novices and also benefitted more from additional peripheral information. Artificial contextual cues about the position of the players did not lead to a predictive advantage, whereas impairing the causal structure of kinematic cues by playing the video in reverse led to a severe impairment. When the videos were flipped vertically to introduce more difficult kinematic cues, predictive behavior was comparable to when observers watching the original videos. Together, these results demonstrate that when contextual information is available in naturalistic scenes, the oculomotor system is successfully integrating them, and is not only relying on low-level information about the target trajectory. Critical factors for successful prediction seem to be the amount of available information, experience with the stimuli and the availability of intact kinematic cues for player movements.
Intrinsic functional connections determine how curiosity and prediction errors enhance memory
Authors: Eschmann Kathrin C. J. , Valji Ashvanti , Graham Kim S. , Lawrence Andrew D. , Gruber Matthias J. 
Published: April 2023

ABSTRACTIndividuals differ in the way they seek information, acquire knowledge, and form memories. Neural finger-prints of intrinsic functional connectivity distinguish between individuals and predict inter-individual differences in task performance. Both curiosity – the desire to acquire new information – and information prediction errors (IPEs) – the mismatch between information and previous expectations – enhance memory but differ considerably between individuals. The present study assessed whether inter-individual differences in functional connectivity measured using resting-state fMRI determine the extent to which individuals benefit from memory-enhancing effects of curiosity and IPEs. We found a double dissociation between individual differences in mesolimbic functional connectivity, which accounted for curiosity-driven but not IPE-related memory enhancements, and individual differences in cingulo-hippocampal functional connectivity, which predicted IPE-driven but not curiosity-related memory enhancements. These novel findings on how inter-individual differences in dissociable intrinsic functional networks determine memory enhancements stress the need to account for these differences in theoretical frameworks of curiosity and memory.