bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics and Practice Patterns of Non-Certified Surgeons Treating Medicare Patients
Authors: Moreci Rebecca , Gates Rebecca S. , Luckoski John , Marcotte Kayla , Mullens Cody L. , Yee Chia Chye , Gupta Tanvi , Kendrick Daniel , Thelen Angela , Krumm Andrew E. , George Brian C.
Published: April 2024

Objective:

The objective of this study is to explore the patient characteristics and practice patterns of non-certified surgeons who treat Medicare patients in the United States.

Background:

Although most surgeons in the United States are board-certified, non-certified surgeons are permitted to practice in many locations. At the same time, surgical workforce shortages threaten access to surgical care for many patients. It is possible that noncertified surgeons may be able to help fill these access gaps. However, little is known about the practice patterns of non-certified surgeons.

Methods:

A 100% sample of Medicare claims data from 2014 to 2019 was used to identify practicing general surgeons. Surgeons were categorized as certified or non-certified in general surgery​​ based on data from the American Board of Surgery. Surgeon practice patterns and patient characteristics were analyzed.

Results:

A total of 2,097,206 patient cases were included in the study. These patients were treated by 16,076 surgeons, of which 6% were identified as non-certified surgeons. Compared with certified surgeons, non-certified surgeons were less frequently fellowship-trained (20.5% vs 24.2%, P=0.008) and more likely to be foreign medical graduates (14.5% vs 9.2%, P<0.001). Non-certified surgeons were more frequently practicing in for-profit hospitals (21.2% vs 14.2%, P<0.001) and critical access hospitals (2.2% vs 1.3%, P<0.001) and were less likely to practice in a teaching hospital (63.2% vs 72.4%, P<0.001). Compared with certified surgeons, non-certified surgeons treated more non-White patients (19.6% vs 14%, P<0.001) as well as a higher percentage of patients in the 2 lowest SES quintiles (36.2% vs 29.2%, P<0.001). Operations related to emergency admissions were more common amongst non-certified surgeons (68.8% vs 55.7%, P<0.001). There were no differences in sex or age of the patients treated by certified and non-certified surgeons.

Conclusions:

For Medicare patients, non-certified surgeons treated more patients who are non-White, of lower socioeconomic status, and in more rural, critical-access hospitals.
Reanimating Pancreatic Grafts Subjected to Prolonged Cold Ischemic Injury Using Normothermic Ex Vivo Perfusion
Authors: Ray Samrat , Parmentier Catherine , Kawamura Masataka , Ganesh Sujani , Nogueira Emmanuel , Novoa Francisco Calderon , Hobeika Christian , Chu Tunpang , Kalimuthu Sangeetha N. , Selzner Markus , Reichman Trevor W.
Published: April 2024

Background.

Pancreas transplant volumes are limited because of poor utilization of “extended criteria grafts.” Prolonged cold ischemia is a risk factor associated with poor allograft survival. We aimed to establish the feasibility of transplantation using grafts subjected to prolonged cold ischemia and determine whether these grafts could be optimized using normothermic ex vivo perfusion (NEVP) in a porcine model.

Methods.

The study population consisted of 35 to 40 kg male Yorkshire pigs in an allotransplantation model with a 3-d survival plan for recipients. Control grafts were subjected to cold storage (CS) in a University of Wisconsin solution for 21 to 24 h (n = 6), whereas the test group received an additional 3 h NEVP after CS of 21 h (n = 5).

Results.

The 3-d survival was 60% in the NEVP arm versus 0% in the control arm (P = 0.008; log rank). Graft parenchyma was 60% to 70% preserved in the NEVP arm at necropsy on gross appearance. In addition, the islet function was well preserved, and both the pancreas (including the islets) and the duodenal morphology were maintained histologically. The intravenous glucose tolerance test on the day of euthanasia was in the normoglycemic range for 80% of cases in the NEVP arm.

Conclusions.

Optimization of pancreas grafts exposed to extended CS with NEVP seems promising at rescuing and reanimating these grafts for transplantation, resulting in significantly improved survival in a porcine pancreas transplant model.
Angiotensin-(1-5) is a Potent Endogenous Angiotensin AT2-Receptor Agonist
Authors: Souza-Silva Igor M. , Peluso A. Augusto , Elsaafien Khalid , Nazarova Antonina L , Assersen Kasper B. , Rodrigues-Ribeiro Lucas , Mohammed Mazher , Rodrigues André F. , Nawrocki Arkadiusz , Jakobsen Lene Andrup , Jensen Pia , de Kloet Annette D. , Krause Eric G. , Borgo Mark Del , Maslov Ivan , Widdop Robert , Santos Robson A. , Bader Michael , Larsen Martin , Verano-Braga Thiago , Katritch Vsevolod , Sumners Colin , Steckelings U. Muscha
Published: April 2024

Background

The renin-angiotensin system involves many more enzymes, receptors and biologically active peptides than originally thought. With this study, we investigated whether angiotensin-(1-5) [Ang-(1-5)], a 5-amino acid fragment of angiotensin II, has biological activity, and through which receptor it elicits effects.

Methods

The effect of Ang-(1-5) (1µM) on nitric oxide release was measured by DAF-FM staining in human aortic endothelial cells (HAEC), or Chinese Hamster Ovary (CHO) cells stably transfected with the angiotensin AT2-receptor (AT2R) or the receptor Mas. A potential vasodilatory effect of Ang-(1-5) was tested in mouse mesenteric and human renal arteries by wire myography; the effect on blood pressure was evaluated in normotensive C57BL/6 mice by Millar catheter. These experiments were performed in the presence or absence of a range of antagonists or inhibitors or in AT2R-knockout mice. Binding of Ang-(1-5) to the AT2R was confirmed and the preferred conformations determined byin silicodocking simulations. The signaling network of Ang-(1-5) was mapped by quantitative phosphoproteomics.

Results

Key findings included: (1) Ang-(1-5) induced activation of eNOS by changes in phosphorylation atSer1177eNOS andTyr657eNOS and thereby (2) increased NO release from HAEC and AT2R-transfected CHO cells, but not from Mas-transfected or non-transfected CHO cells. (3) Ang-(1-5) induced relaxation of preconstricted mouse mesenteric and human renal arteries and (4) lowered blood pressure in normotensive mice – effects which were respectively absent in arteries from AT2R-KO or in PD123319-treated mice and which were more potent than effects of the established AT2R-agonist C21. (5) According toin silicomodelling, Ang-(1-5) binds to the AT2R in two preferred conformations, one differing substantially from where the first five amino acids within angiotensin II bind to the AT2R. (6) Ang-(1-5) modifies signaling pathways in a protective RAS-typical way and with relevance for endothelial cell physiology and disease.

Conclusions

Ang-(1-5) is a potent, endogenous AT2R-agonist.
DCLK1-Mediated Regulation of Invadopodia Dynamics and Matrix Metalloproteinase Trafficking Drives Invasive Progression in Head and Neck Squamous Cell Carcinoma
Authors: Arnold Levi , Yap Marion , Jackson Laura , Barry Michael , Ly Thuc , Morrison Austin , Gomez Juan P. , Washburn Michael P. , Standing David , Yellapu Nanda Kumar , Li Linheng , Umar Shahid , Anant Shrikant , Thomas Sufi Mary
Published: April 2024

Head and neck squamous cell carcinoma (HNSCC) is a major health concern due to its high mortality from poor treatment responses and locoregional tumor invasion into life sustaining structures in the head and neck. A deeper comprehension of HNSCC invasion mechanisms holds the potential to inform targeted therapies that may enhance patient survival. We previously reported that doublecortin like kinase 1 (DCLK1) regulates invasion of HNSCC cells. Here, we tested the hypothesis that DCLK1 regulates proteins within invadopodia to facilitate HNSCC invasion. Invadopodia are specialized subcellular protrusions secreting matrix metalloproteinases that degrade the extracellular matrix (ECM). Through a comprehensive proteome analysis comparing DCLK1 control and shDCLK1 conditions, our findings reveal that DCLK1 plays a pivotal role in regulating proteins that orchestrate cytoskeletal and ECM remodeling, contributing to cell invasion. Further, we demonstrate in TCGA datasets that DCLK1 levels correlate with increasing histological grade and lymph node metastasis. We identified higher expression of DCLK1 in the leading edge of HNSCC tissue. Knockdown of DCLK1 in HNSCC reduced the number of invadopodia, cell adhesion and colony formation. Using super resolution microscopy, we demonstrate localization of DCLK1 in invadopodia and colocalization with mature invadopodia markers TKS4, TKS5, cortactin and MT1-MMP. We carried out phosphoproteomics and validated using immunofluorescence and proximity ligation assays, the interaction between DCLK1 and motor protein KIF16B. Pharmacological inhibition or knockdown of DCLK1 reduced interaction with KIF16B, secretion of MMPs, and cell invasion. This research unveils a novel function of DCLK1 within invadopodia to regulate the trafficking of matrix degrading cargo. The work highlights the impact of targeting DCLK1 to inhibit locoregional invasion, a life-threatening attribute of HNSCC.
Repeated LPS induces training and tolerance of microglial responses across brain regions
Authors: Kim Jennifer , Sullivan Olivia , Lee Kristen , Jao Justin , Tamayo Juan , Madany Abdullah Muhammad , Wong Brandon , Ashwood Paul , Ciernia Annie Vogel
Published: April 2024

Background

Neuroinflammation is involved in the pathogenesis of almost every central nervous system disorder. As the brain’s innate immune cells, microglia fine tune their activity to a dynamic brain environment. Previous studies have shown that repeated bouts of peripheral inflammation can trigger long-term changes in microglial gene expression and function, a form of innate immune memory.

Methods and Results

In this study, we used multiple low-dose lipopolysaccharide (LPS) injections in adult mice to study the acute cytokine, transcriptomic, and microglia morphological changes that contribute to the formation of immune memory in the frontal cortex, hippocampus, and striatum, as well as the long-term effects of these changes on behavior. Training and tolerance of gene expression was shared across regions, and we identified 3 unique clusters of DEGs (2xLPS-sensitive, 4xLPS-sensitive, LPS-decreased) with different biological functions. 2xLPS-sensitive DEG promoters were enriched for binding sites for IRF and NFkB family transcription factors, two key regulators of innate immune memory. We quantified shifts in microglia morphological populations and found that while the proportion of ramified and rod-like microglia mostly remained consistent within brain regions and sexes with LPS treatment, there was a shift from ameboid towards hypertrophic morphological states across immune memory states and a dynamic emergence and resolution of trains of rod-like microglia with repeated LPS.

Conclusions

Together, findings support the dynamic regulation of microglia during the formation of immune memories in the brain and support future work to exploit this model in brain disease contexts.
scRCA: a Siamese network-based pipeline for the annotation of cell types using imperfect single-cell RNA-seq reference data
Authors: Liu Yan , Li Chen , Shen Long-Chen , Yan He , Wei Guo , Gasser Robin B. , Hu Xiaohua , Song Jiangning , Yu Dong-Jun
Published: April 2024

A critical step in the analysis of single-cell transcriptomic (scRNA-seq) data is the accurate identification and annotation of cell types. Such annotation is usually conducted by comparative analysis with known (reference) data sets – which assumes an accurate representation of cell types within the reference sample. However, this assumption is often incorrect, because factors, such as human errors in the laboratory or in silico, and methodological limitations, can ultimately lead to annotation errors in a reference dataset. As current pipelines for single-cell transcriptomic analysis do not adequately consider this challenge, there is a major demand for a computational pipeline that achieves high-quality cell type annotation using imperfect reference datasets that contain inherent errors (often referred to as “noise”). Here, we built a Siamese network-based pipeline, termed scRCA, that achieves an accurate annotation of cell types employing imperfect reference data. For researchers to decide whether to trust the scRCA annotations, an interpreter was developed to explore the factors on which the scRCA model makes its predictions. We also implemented 3 noise-robust losses-based cell type methods to improve the accuracy using imperfect dataset. Benchmarking experiments showed that scRCA outperforms the proposed noise-robust loss-based methods and methods commonly in use for cell type annotation using imperfect reference data. Importantly, we demonstrate that scRCA can overcome batch effects induced by distinctive single cell RNA-seq techniques. We anticipate that scRCA (https://github.com/LMC0705/scRCA) will serve as a practical tool for the annotation of cell types, employing a reference dataset-based approach.
A single cell atlas of the mouse seminal vesicle
Authors: Sun Fengyun , Desevin Kathleen , Fu Yu , Parameswaran Shanmathi , Mayall Jemma , Rinaldi Vera , Krietenstein Nils , Manukyan Artur , Yin Qiangzong , Galan Carolina , Yang Chih-Hsiang , Shindyapina Anastasia V. , Gladyshev Vadim N. , Garber Manuel , Schjenken John E. , Rando Oliver J.
Published: April 2024

During mammalian reproduction, sperm are delivered to the female reproductive tract bathed in a complex medium known as seminal fluid, which plays key roles in signaling to the female reproductive tract and in nourishing sperm for their onwards journey. Along with minor contributions from the prostate and the epididymis, the majority of seminal fluid is produced by a somewhat understudied organ known as the seminal vesicle. Here, we report the first single-cell RNA-seq atlas of the mouse seminal vesicle, generated using tissues obtained from 23 mice of varying ages, exposed to a range of dietary challenges. We define the transcriptome of the secretory cells in this tissue, identifying a relatively homogeneous population of the epithelial cells which are responsible for producing the majority of seminal fluid. We also define the immune cell populations – including large populations of macrophages, dendritic cells, T cells, and NKT cells – which have the potential to play roles in producing various immune mediators present in seminal plasma. Together, our data provide a resource for understanding the composition of an understudied reproductive tissue with potential implications for paternal control of offspring development and metabolism.
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

Pannexin (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 summary

Pannexin 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

The 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

Drosophilaestablishes 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

Background

Motor 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.

Methods

We 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.

Results

The 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.

Conclusions

This 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

perox-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

With 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

The 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.

Importance

Photosynthetic 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

The 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

Single-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

Corals 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

From 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.
Genomics and synthetic community experiments uncover the key metabolic roles of acetic acid bacteria in sourdough starter microbiomes
Authors: Rappaport H. B. , Senewiratne Nimshika P. J. , Lucas Sarah K , Wolfe Benjamin E. , Oliverio Angela M
Published: April 2024

While research on the sourdough microbiome has primarily focused on lactic acid bacteria (LAB) and yeast, recent studies have found that acetic acid bacteria (AAB) are also common members. However, the ecology, genomic diversity, and functional contributions of AAB in sourdough remain unknown. To address this gap, we sequenced 29 AAB genomes, including three that represent putatively novel species, from a collection of over 500 sourdough starters surveyed globally from community scientists. We found variation in metabolic traits related to carbohydrate utilization, nitrogen metabolism, and alcohol production, as well as in genes related to mobile elements and defense mechanisms. Sourdough AAB genomes did not cluster when compared to AAB isolated from other environments, although a subset of gene functions were enriched in sourdough isolates. The lack of a sourdough-specific genomic cluster may reflect a nomadic lifestyle of AAB. To assess the consequences of AAB on the emergent function of sourdough starter microbiomes, we constructed synthetic starter microbiomes, varying only the AAB strain included. All AAB strains increased acidification of synthetic sourdough starters relative to yeast and LAB by 18.5% on average. Different strains of AAB had distinct effects on the profile of synthetic starter volatiles. Taken together, our results begin to define the key ways in which AAB shape emergent properties of starters and suggest that differences in gene content resulting from intraspecies diversification can have community-wide consequences on emergent function.
A defining member of the new cysteine-cradle family is an aECM protein signalling skin damage inC. elegans
Authors: Sonntag Thomas , Omi Shizue , Andreeva Antonina , Eichelbrenner Jeanne , Chisholm Andrew D , Ward Jordan D , Pujol Nathalie
Published: April 2024

Apical extracellular matrices (aECMs) act as crucial barriers, and communicate with the epidermis to trigger protective responses following injury or infection. In Caenorhabditis elegans, the skin aECM, the cuticle, is produced by the epidermis and decorated with circumferential furrows. We previously showed that mutants lacking cuticle furrows exhibit persistent immune activation (PIA). In a genetic suppressor screen, we identified spia-1 as a key gene downstream of furrow collagens and upstream of immune signalling. spia-1 expression oscillates during larval development, peaking between each moult together with patterning cuticular components. It encodes a secreted protein that localises to furrows. SPIA-1 shares a novel cysteine-cradle domain with other aECM proteins. SPIA-1 mediates immune activation in response to furrow loss and is proposed to act as a sensor of cuticle damage. This research provides the first molecular insight into an intricate interplay between cuticle integrity and epidermal immune activation inC. elegans.
Verbal semantic expertise is associated with reduced functional connectivity between left and right anterior temporal lobes
Authors: Wu Wei , Hoffman Paul
Published: April 2024

The 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.
BEYOND UNIFORMITY: Pyomelanin’s structural complexity impacts on UV shielding inPseudomonasspecies with different lifestyles
Authors: Diaz Appella Mateo N. , Kolender Adriana , Oppezzo Oscar J. , López Nancy I. , Tribelli Paula M.
Published: April 2024

Melanin, a polymeric pigment synthesized by various organisms, confers advantageous traits, including heightened resistance to stress agents. InPseudomonas, disruption of the tyrosine degradation pathway leads to pyomelanin production. Despite a shared synthetic pathway, the chemical structure of pyomelanin remains elusive due to its heterogeneous polymeric nature, suggesting composition variations even among closely related species. Our objective was to analyze pyomelanin structural features acrossPseudomonasstrains: CRISPR/nCas9-engineeredhmgAmutants of PAO1 and PA14, reference strains of the human opportunist pathogenP. aeruginosa; a natural melanogenic mutant (PAM) from a patient; and a Tn5 mutant of the extremophile bacteriumP. extremaustralis(PexM). Structural analysis revealed strain-specific differences. UV spectra exhibited dual peaks for PAO1 and PA14 mutants, while PAM and PexM displayed a single peak. FTIR indicated changes in the alcohol content ratio, with PAO1 and PA14hmgAmutants having a near 1:1 ratio, PexM a dominant phenol band, and PAM a predominance of the alcohol band. Complex NMR spectra suggested non-linear polymers composed by substituted phenolic rings, carboxylic acids, and alkyl chains, highlighting inter-pigment disparities. UVC (254 nm) susceptibility assessment showed increased survival with pyomelanin addition, correlating with the attenuation of the incoming radiation due to absorption in the culture medium. Moreover, survival to UVC ofP. extremaustraliswas different depending on the melanin source being the most protective pyomelanin obtained from PAO1. These findings reveal distinct pyomelanin subgroups based on structure among strains, elucidating varied physiological effects.
Microtubule networks in zebrafish hair cells facilitate presynapse transport and fusion during development
Authors: Hussain Saman , Pinter Katherine , Uhl Mara , Wong Hiu-Tung , Kindt Katie
Published: April 2024

Sensory cells in the retina and inner ear rely on specialized ribbon synapses for neurotransmission. Disruption of these synapses is linked to visual and auditory dysfunction, but it is unclear how these unique synapses are formed. Ribbon synapses are defined by a presynaptic density called a ribbon. Using live-imaging approaches in zebrafish, we find that early in hair-cell development, many small ribbon precursors are present throughout the cell. Later in development, fewer and larger ribbons remain, and localize at the presynaptic active zone (AZ). Using tracking analyses, we show that ribbon precursors exhibit directed motion along an organized microtubule network towards the presynaptic AZ. In addition, we show that ribbon precursors can fuse together on microtubules to form larger ribbons. Using pharmacology, we find that microtubule disruption interferes with ribbon motion, fusion, and normal synapse formation. Overall, this work demonstrates a dynamic series of events that underlies formation of a critical synapse required for sensory function.
Beam gas curtain monitor: Vacuum studies for LHC integration and operation
Authors: Castro Sequeiro C. , Ady M. , Bregliozzi G. , Chatzigeorgiou N. , Churchman A. R. , Kersevan R. , Lefevre T. , Mazzoni S. , Pigny G. , Rossi A. , Sameed M. , Schneider G. , Sedlacek O. , Sidorowski K. , Vazquez Pelaez C. , Veness R. , Zygaropoulos L. , Stringer O. , Webber-Date A. , Welsch C. P. , Zhang H. , Forck P. , Udrea S.
Published: April 2024

A beam gas curtain (BGC) monitor has been designed to obtain information about the relative position between the LHC proton beam and the hollow electron lens electron beam through a minimally invasive process. Its working principle relies on intersecting the path of both beams with a supersonic gas curtain, introduced transversely into the LHC beamline, to produce a fluorescence signal. As an intermediate project stage (phase II), a preliminary version of the BGC monitor has been installed into the LHC beamline. To ensure the successful integration of the monitor and subsequent operation under LHC ultrahigh vacuum conditions, a series of vacuum studies have been performed. These can be classified as follows: An off-line laboratory test campaign, to assess BGC behavior during pump down and gas injections; simulations and analytical calculations, to evaluate BGC behavior and estimate the impact of its installation and operation in the LHC. This document will briefly present the off-line tests campaign, followed by a more extensive description of the simulations performed.

Published by the American Physical Society
2024
Experimental observation of a mode-1 instability driven by Landau cavities in a storage ring
Authors: Cullinan F. J. , Andersson Å. , Breunlin J. , Brosi M. , Tavares P. F.
Published: April 2024

Landau cavities used to lengthen the bunches in storage rings necessarily constitute a significant impedance. Because of the particular phase of the field required for bunch lengthening, they are often detuned quite considerably from resonance, more so than the main cavities. As a result, their impedance can excite the first coupled-bunch mode such that it becomes unstable. This phenomenon has previously been predicted [M. Venturini, ] and characterized in simulations [T. He, ] but experimental observation is yet to be documented. In this paper, the experimental observation of coupled-bunch modes-±1 excited by the Landau and main cavities in a fourth-generation light-source storage ring is presented. Features of the instability such as amplitude and coherent frequency at saturation have been measured and its dependency on the main rf voltage has been explored. The impact of a parked main cavity has also been investigated.

Published by the American Physical Society
2024
Nonlocal Elasticity Yields Equilibrium Patterns in Phase Separating Systems
Authors: Qiang Yicheng , Luo Chengjie , Zwicker David
Published: April 2024

Recent experiments demonstrated the emergence of regular mesoscopic patterns when liquid droplets form in an elastic gel after cooling. These patterns appeared via a continuous transition and were smaller in stiffer systems. We capture these observations with a phenomenological equilibrium model describing the density field of the elastic component to account for phase separation. We show that local elasticity theories are insufficient, even if they allow large shear deformations. Instead, we can account for key observations using a nonlocal elasticity theory to capture the gel’s structure. Analytical approximations unveil that the pattern period is determined by the geometric mean between the elastocapillary length and a nonlocality scale. Our theory highlights the importance of nonlocal elasticity in soft matter systems, reveals the mechanism of this mesoscopic pattern, and will improve the engineering of such systems.

Published by the American Physical Society
2024