bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pannexin 1 and Pannexin 3 differentially regulate the tumorigenic properties of cutaneous squamous cell carcinoma
Authors: O’Donnell Brooke L. , Johnston Danielle , Bhatt Ayushi , Kardan Zahra , Stefan Dan , Bysice Andrew , Sayedyahossein Samar , Dagnino Lina , Cecchini Matthew , Loganathan Sampath Kumar , Roth Kathryn , Penuela Silvia 
Published: April 2024

AbstractPannexin (PANX) channels are present in skin and facilitate the movement of signalling molecules during cellular communication. PANX1 and PANX3 function in skin homeostasis and keratinocyte differentiation but were previously reduced in a small cohort of human cutaneous squamous cell carcinoma (cSCC) tumours compared to normal epidermis. In our study, we used SCC-13 cells, limited publicly available RNA-seq data and a larger cohort of cSCC patient-matched samples to analyze PANX1 and PANX3 expression and determine the association between their dysregulation and the malignant properties of cSCC. In a bioinformatics analysis,PANX1transcripts were increased in cSCC and head and neck SCC tumours compared to normal tissues, butPANX3mRNA showed no differences. However, in our own cohort,PANX3transcripts were decreased in cSCC compared to patient-matched aged skin, whereas PANX1 was upregulated in cSCC. PANX1 localized to all regions within the cSCC tumour microenvironment and increased levels were associated with larger tumour dimensions. To investigate PANX1 function in SCC-13 cells, we deletedPANX1via CRISPR/Cas9 and treated with PANX1 inhibitors which markedly reduced cell growth and migration. To assess PANX3 function in cutaneous carcinogenesis, we employed the DMBA/TPA model using our globalPanx3knockout (KO) mice, where 60% of wildtype and 100% of KO mice formed pre-cancerous papillomas. Average papilloma volumes at endpoint were significantly increased in KO mice and showed moderate evidence of increases in KO mice over time. Collectively, these findings suggest PANX1 and PANX3 dysregulation may have potential tumour promoting and suppressive effects for keratinocyte transformation, respectively.Key points summaryPannexin 1 and pannexin 3 are channel-forming proteins which are critical in the normal maintenance and function of keratinocytes in the skin but may become altered in cutaneous squamous cell carcinoma (cSCC) tumours.In this study, we used a combination of culture models, mouse models and patient-derived tissues. We found pannexin 1 levels are increased in cSCC tumours and present in all tumour regions, functioning to promote cSCC cell growth and migration.Conversely, pannexin 3 levels are decreased in cSCC tumours and this protein reduces the incidence and growth of pre-cancerous lesions.Taken together, our data indicates that in cSCC these pannexin family members seem to have opposite effects, where pannexin 1 is pro-tumorigenic and pannexin 3 is anti-tumorigenic.These results help us to better understand the mechanisms of malignant transformation of keratinocytes and offer a new potential therapeutic target for the treatment of advanced cSCC.
Valproic Acid Treatment Enhances Chromosome Flexibility and Electron Transport in MCF7 Breast Cancer Cells
Authors: Agrawal Tanya , Paul Debashish , Mishra Amita , Ganesan Arunkumar , Pal Suchetan , Rakshit Tatini 
Published: April 2024

AbstractThe structural integrity of the chromosomes is essential to every functional process within the eukaryotic nuclei. Chromosomes are DNA-histone complexes essential for the inheritance of genetic information to the offspring and any defect in it is linked to mitotic errors, cancer growth, and cellular aging. Changes in the mechanical properties of a chromosome could lead to its compromised function and stability, leading to chromosome breaks. Here, we studied the changes in chromosome physical properties using metaphase chromosomes isolated from human breast cancer cells (MCF7) exposed to Valproic Acid (VPA), a known epigenetic modifier drug involved in histone hyperacetylation and DNA demethylation. Due to chromosomal structural intricacy, preparative and technical limitations of analytical tools, we employed a label-free atomic force microscopy approach for simultaneously visualizing and mapping single chromosome elasticity. Additionally, we performed electron transport characteristics of metaphase chromosomes to elucidate the effect of VPA. Our multi-parametric strategy of probing physical properties of chromosomes offers a new scope in terms of analytical tools for studying chromosomal structural changes/aberrations and associated structure-function relationships pertinent to cancer.
Drosulfakininsignaling encodes early-life memory for adaptive social plasticity
Authors: Jeong Jiwon , Kwon Kujin , Geisseova Terezia Klaudia , Lee Jongbin , Kwon Taejoon , Lim Chunghun 
Published: April 2024

AbstractDrosophilaestablishes social clusters in groups, yet the underlying principles remain poorly understood. Here we performed a systemic analysis of social network behavior (SNB) that quantifies individual social distance (SD) in a group over time. The SNB assessment in 175 inbred strains from the Drosophila Genetics Reference Panel revealed a tight association of short SD with long developmental time, low food intake, and hypoactivity. The developmental inferiority in short-SD individuals was compensated by their group culturing. By contrast, developmental isolation silenced the beneficial effects of social interactions in adults and blunted the plasticity of SNB under physiological challenges. Transcriptome analyses showed genetic diversity for SD traits, whereas social isolation reprogrammed select genetic pathways, regardless of SD phenotypes. In particular, social deprivation suppressed the expression of the neuropeptide Drosulfakinin (Dsk) in three pairs of adult brain neurons. Male-specific DSK signaling to Cholecystokinin-like receptor 17D1 mediated the SNB plasticity. In fact, transgenic manipulations of the DSK signaling were sufficient to imitate the state of social experience. Given the functional conservation of mammalianDskhomologs, we propose that animals have evolved a dedicated neural mechanism to encode early-life experience and transform group properties adaptively.
MOTOR MODULES ARE LARGELY UNAFFECTED BY PATHOLOGICAL WALKING BIOMECHANICS: A SIMULATION STUDY
Authors: Goloujeh Mohammad Rahimi , Allen Jessica L. 
Published: April 2024

AbstractBackgroundMotor module (a.k.a. muscle synergy) analysis has frequently been used to provide insight into changes in muscle coordination associated with declines in walking performance, to evaluate the effect of different rehabilitation intervention, and more recently, to control exoskeletons and prosthetic devices. However, it remains unclear whether changes in muscle coordination revealed via motor module analysis stem from pathological walking biomechanics or pathological neural control. This distinction has important implications for the use of motor module analysis for rehabilitation interventions and device design. Thus, this study aims to elucidate the extent to which motor modules emerge from pathological walking biomechanics.MethodsWe conducted a series of computer simulations using OpenSim Moco to simulate abnormal biomechanics by manipulating speed, asymmetry, and step width in a three-dimensional musculoskeletal model. We extracted motor modules using nonnegative matrix factorization from the muscle activation from each simulation. We then examined how alterations in walking biomechanics influenced the number and structure of extracted motor modules and compared the findings to previous experimental studies.ResultsThe motor modules identified from our simulations were similar to those identified from previously published experiments of non-pathological walking. Moreover, our findings indicate that the same motor modules can be used to generate a range of pathological-like waking biomechanics by modulating their recruit timing over the gait cycle. These results contrast with experimental studies in which pathological-like walking biomechanics are accompanied by a reduction in motor module number and alterations in their structure.ConclusionsThis study highlights that pathological walking biomechanics do not necessarily require pathological motor modules. In other words, changes in number and structure of motor modules can be a valuable indicator of alterations in neuromuscular control and may therefore be useful for guiding rehabilitation interventions and controlling exoskeletons and prosthetic devices in individuals with pathological walking function.
Automated, image-based quantification of peroxisome characteristics withperox-per-cell
Authors: Neal Maxwell L. , Shukla Nandini , Mast Fred D. , Farré Jean-Claude , Pacio Therese M. , Raney-Plourde Katelyn E. , Prasad Sumedh , Subramani Suresh , Aitchison John D. 
Published: April 2024

ABSTRACTperox-per-cellautomates cumbersome, image-based data collection tasks often encountered in peroxisome research. The software processes microscopy images to quantify peroxisome features in yeast cells. It uses off-the-shelf image processing tools to automatically segment cells and peroxisomes and then outputs quantitative metrics including peroxisome counts per cell and spatial areas. In validation tests, we found thatperox-per-celloutput agrees well with manually-quantified peroxisomal counts and cell instances, thereby enabling high-throughput quantification of peroxisomal characteristics. The software is available athttps://github.com/AitchisonLab/perox-per-cell
RT-Sort: an action potential propagation-based algorithm for real time spike detection and sorting with millisecond latencies
Authors: van der Molen Tjitse , Lim Max , Bartram Julian , Cheng Zhuowei , Robbins Ash , Parks David F. , Petzold Linda R. , Hierlemann Andreas , Haussler David , Hansma Paul K. , Tovar Kenneth R. , Kosik Kenneth S. 
Published: April 2024

AbstractWith the use of high density multi electrode recording devices, electrophysiological signals resulting from action potentials of individual neurons can now be reliably detected on multiple adjacent recording electrodes bothin vivoandin vitro. Spike sorting assigns these signals to putative neural sources. However, until now, spike sorting can only be performed after completion of the recording, preventing true real time usage of spike sorting algorithms. Utilizing the unique propagation patterns of action potentials along axons detected as high fidelity sequential activations on adjacent electrodes, together with a convolutional neural network based spike detection algorithm, we introduce RT-Sort (Real Time Sorting), a spike sorting algorithm that enables the sorted detection of action potentials within 7.5ms±1.5ms (mean±STD) after the waveform trough while the recording remains ongoing. RT-Sort’s true real-time spike sorting capabilities enable closed loop experiments with latencies comparable to synaptic delay times. We show RT-Sort’s performance on both Multi-Electrode Arrays as well as Neuropixels probes to exemplify RT-Sort’s functionality on different types of recording hardware and electrode configurations.
Microevolution toward loss of photosynthesis: Mutations promoting dark-heterotrophic growth and suppressing photosynthetic growth in cyanobacteria
Authors: Hida Shintaro , Nishio Marie , Uesaka Kazuma , Banba Mari , Takatani Nobuyuki , Takaichi Shinichi , Yamamoto Haruki , Ihara Kunio , Fujita Yuichi 
Published: April 2024

SummaryThe prevalence of parasitic plants suggests frequent evolution of photosynthetic capacity loss in the natural environment. However, no studies have observed such evolutionary events as a loss of photosynthetic capacity. Herein, we report mutations that lead to a loss or decrease in photosynthetic growth capacity of dark-adapted variants of the cyanobacteriumLeptolyngbya boryana, which can grow heterotrophically even in the dark. We isolated 28 dark-adapted variants through long-term cultivation (7–49 months) under dark-heterotrophic conditions. All variants showed significantly faster dark-heterotrophic growth than the parental strains, accompanied by the loss of photosynthetic growth capacity in 15 variants. Genome resequencing of the variants revealed that 19 of the 28 variants carried various mutations in a common single gene (LBDG_21500) encoding a protein phosphatase 2C (PP2C) RsbU that is involved in the partner switching system (PSS). Phenotypic and transcriptomic analyses of aLBDG_21500-knockout mutant suggested that the PSS, including LBDG_21500, is involved in the global transcriptional regulation of various genes under both photoautotrophic and dark-heterotrophic conditions. We propose the renaming ofLBDG_21500tophsP(phototrophic–heterotrophic switching phosphatase). Our results imply that mutations in the global transcriptional regulatory system serve as the first evolutionary step leading to the loss of photosynthetic capacity.ImportancePhotosynthetic organisms that grow using minimal resources: light, water, and CO2, support most heterotrophic organisms as producers on the Earth. When photosynthetic organisms thrive over long generations under environments where organic compounds are readily available, they may lose the photosynthetic capacity because of the relief of selective pressure to maintain photosynthesis. The prevalence of parasitic plants in the natural environment supports this idea. However, there have been no actual observations of evolutionary processes leading to a loss of photosynthetic growth capacity. The significance of our research is in observing microevolution of a cyanobacterium through a long-term cultivating under dark heterotrophic conditions. In particular, the high frequency of mutations to a gene involved in the global transcriptional regulatory system suggests that such mutations in regulatory systems are regarded as an example of the initial evolutionary processes toward complete loss of photosynthesis.
Neuronal and non-neuronal functions of the synaptic cell adhesion molecule, neurexin, inNematostella vectensis
Authors: Guzman Christine , Mohri Kurato , Tsuchiya Yuko , Tomii Kentaro , Watanabe Hiroshi 
Published: April 2024

AbstractThe transition from diffusion-mediated cell-cell communication to faster and more targeted synaptic signaling in animal nervous systems has long been of interest to evolutionary biologists. Although genome sequencing of early-diverging metazoans has revealed the broad distribution of synapse-related genes among them, synaptic structures have been observed only in Cnidaria, the sister group to Bilateria. How synaptic machinery evolved remains largely unknown. In this study, we investigated the function of neurexins (Nrxns), a core family of presynaptic cell adhesion molecules with critical roles in bilaterian chemical synapses, using the cnidarian model,Nematostella vectensis. Neural Nrxns, named delta-Nrxns, are expressed mainly in neuronal cell clusters that exhibit both peptidergic and classical neurotransmitter signaling. Knockdown of Nrxnδ genes reduced spontaneous peristalsis ofN. vectensispolyps. Interestingly, gene knockdown and pharmacological studies suggested that Nrxnδ is involved in glutamate- and glycine-mediated signaling rather than peptidergic signaling. Knockdown of the epithelial Nrxn inN. vectensisrevealed a major role in cell adhesion, particularly between ectodermal and endodermal epithelia. Overall, this study provides molecular, functional, and cellular insights into the ancestral, non-neural function of Nrxns, as well as key information for understanding how and why this family of cell adhesion molecules was recruited to synaptic machinery.
scPanel: A tool for automatic identification of sparse gene panels for generalizable patient classification using scRNA-seq datasets
Authors: Xie Yi , Yang Jianfei , Ouyang John F , Petretto Enrico 
Published: April 2024

AbstractSingle-cell RNA sequencing (scRNA-seq) technologies can generate transcriptomic profiles at a single-cell resolution in large patient cohorts, facilitating discovery of gene and cellular biomarkers for disease. Yet, when the number of biomarker genes is large the translation to clinical applications is challenging due to prohibitive sequencing costs. Here we introduce scPanel, a computational framework designed to bridge the gap between biomarker discovery and clinical application by identifying a minimal gene panel for patient classification from the cell population(s) most responsive to perturbations (e.g., diseases/drugs). scPanel incorporates a data-driven way to automatically determine the number of selected genes. Patient-level classification is achieved by aggregating the prediction probabilities of cells associated with a patient using the area under the curve score. Application of scPanel on scleroderma and COVID-19 datasets resulted in high patient classification accuracy using a small number (<20) of genes automatically selected from the entire transcriptome. We demonstrate 100% cross-dataset accuracy to predict COVID-19 disease state on an external dataset, illustrating the generalizability of the predicted genes. scPanel outperforms other state-of-the-art gene selection methods for patient classification and can be used to identify small sets of reliable biomarker candidates for clinical translation.
Modeling Symbiont Dynamics and Coral Regulation under Changing Temperatures*
Authors: Cavailles Jerome , Kuzmics Christoph , Grube Martin 
Published: April 2024

AbstractCorals play an essential role in marine ecosystems by creating protective coastal structures and habitats for marine biodiversity. Their symbiotic relationship with various algal species, where corals supply nitrogen in exchange for carbon products, is vital for their survival. However, with some algal species being temperature sensitive, this vital symbiosis is increasingly threatened by global warming, causing significant symbiont losses, potentially leading to coral bleaching and fatal consequences. Here, we model the optimal regulation of algal populations by corals through nitrogen allocation. Two algal species compete for nitrogen: one is effective in carbon supply and rapid growth, and the other is resilient to temperature increases. Our testable analytical solution identifies the optimal total algal population as a function of the current temperature and symbiont composition. The model also determines the relative abundances of the two algal species based on current and historical temperatures. Our findings are consistent with numerous previous observations and experimental studies. The model clarifies how inter-species competition under varying temperature patterns shapes the composition and dynamics of algal species in coral symbiosis. It also clarifies that bleaching occurs when the relatively efficient algae fail to exchange enough carbon products at high temperatures.
Confirmation of Highly Pathogenic Avian Influenza (HPAI) H5N1 Associated with an Unexpected Mortality Event in South Polar Skuas (Stercorarius maccormicki) during 2023-2024 Surveillance Activities in Antarctica
Authors: Bennett Lazo Benjamín , Berazay Bárbara , Muñoz Gabriela , Ariyama Naomi , Enciso Nikita , Braun Christina , Krüger Lucas , Barták Miloš , González-Aravena Marcelo , Neira Victor 
Published: April 2024

AbstractFrom December 2023 to March 2024, a surveillance program to detect HPAI H5N1 was performed on Antarctica Territory, at Fildes Peninsula (King George Island, Maritime Antarctic), and James Ross Island. At Fildes Peninsula, samples from marine birds and mammals from four sampling locations were collected, based on their accessibility and the presence of animal colonies: Ardley Island, which presents a high concentration of Gentoo penguins (Pygoscelis papua); Ardley Cove were small groups of likely non-reproductive Chinstrap penguins (Pygoscelis antarcticus); Southern elephant (Mirounga leonina) and Weddell (Leptonycotes wedellii) seals haul-out sites; and, a nesting site of Southern giant petrels (Macronectes giganteus). On February 28ththe surveillance group received a request for sample collection, due to the observation of deceased seabirds at James Ross Island in the area neighboring the Lachman lakes (63.7989 S, 57.8105 W). Six samples from five dead South polar skuas (Stercorarius maccormicki) were collected on March 3rd, 2024. All samples were collected adhering to the Antarctic Treaty guidelines. After collecting a total of 943 samples from Fildes Peninsula all results tested negative, and no individuals had clinical signs or behaviors compatible with HPAI. However, all samples from South polar skuas from James Ross Island were confirmed positive for HPAI H5N1 clade 2.3.4.4 by specific real-time RT-PCR reactions. These results confirmed the first mortality event registered in Antarctica (south of 60°S) caused by HPAI H5N1, in this case on South polar skuas. Further studies are needed to genetically characterize the virus and to better understand the role of skuas in the dynamics of viral dissemination in Antarctica.
Verbal semantic expertise is associated with reduced functional connectivity between left and right anterior temporal lobes
Authors: Wu Wei , Hoffman Paul 
Published: April 2024

AbstractThe left and right anterior temporal lobes (ATLs) encode semantic representations. They show graded hemispheric specialisation in function, with the left ATL contributing preferentially to verbal semantic processing. We investigated the underlying causes of this organisation, using resting-state functional connectivity as a measure of functional segregation between ATLs. We analysed two independent resting-state fMRI datasets (N=86 and N=642) in which participants’ verbal semantic expertise was measured using vocabulary tests. In both datasets, people with more advanced verbal semantic knowledge showed weaker functional connectivity between left and right ventral ATLs. This effect was highly specific. It was not observed for within-hemisphere connections between semantic regions (ventral ATL and inferior frontal gyrus; IFG, though it was found for left-right IFG connectivity in one dataset). Effects were not found for tasks probing semantic control, non-semantic cognition or face recognition. Our results suggest that hemispheric specialisation in the ATLs is not an innate property but rather emerges as people develop highly detailed verbal semantic representations. We propose that this effect is a consequence of the left ATL’s greater connectivity with left-lateralised written word recognition regions, which causes it to preferentially represent meaning for advanced vocabulary acquired primarily through reading.