bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uncertainty propagation in matrix population models: gaps, importance, and guidelines
Authors: Simmonds Emily G. , Jones Owen R. 
Published: August 2023

AbstractMatrix population models (MPMs), which describe the demographic behaviour of a population based on age or stage through discrete time, are popular in ecology, evolutionary biology, and conservation biology. MPMs provide a tool for guiding management decisions and can give insight into life history trade-offs, patterns of senescence, transient dynamics, and population trajectories. These models are parameterised with estimates of vital rates (e.g. survival and reproduction) and can have multiple layers of underlying statistical analyses, all of which introduce uncertainty. For accurate and transparent results, this uncertainty should be propagated through to quantities derived from the MPMs. However, full propagation is not always achieved, leading to omitted uncertainty, and negative consequences for the reliability of inferences drawn.We summarised the state-of-the-art regarding vital rate uncertainty reporting and propagation, by reviewing papers using MPMs from 2010-2019. We then used reported uncertainties as the basis for a simulation study to explore the impact of uncertainty omission on inferences drawn from the analysis of MPMs. We simulated four scenarios of vital rate propagation and evaluated their impact on population growth rate estimates.Although around 78% of MPM papers report some kind of uncertainty in their findings, only half of those report uncertainty in all aspects. Additionally, only 31% of papers fully propagate uncertainty through to derived quantities. Our simulations demonstrate that, even under a median uncertainty level, incomplete propagation introduces bias. Omitting uncertainty may substantially alter conclusions, particularly for results showing small changes in population size. Biased conclusions were most common when uncertainty in the most influential vital rates for population growth were omitted.We suggest comprehensive guidelines for reporting and propagating uncertainty in MPMs. Standardising methods and reporting will increase the reliability of MPMs and enhance the comparability of different models. These guidelines will improve the accuracy, transparency, and reliability of population projections, increasing our confidence in results that can inform conservation efforts, ultimately contributing to biodiversity preservation.
Loss of NMDA receptor function during development results in decreased KCC2 expression and increased neurons in the zebrafish forebrain
Authors: Napoli Amalia J. , Laderwager Stephanie , Zoodsma Josiah D. , Biju Bismi , Mucollari Olgerta , Schubel Sarah K. , Aprea Christieann , Sayed Aaliya , Morgan Kiele , Napoli Annelysia , Flanagan Stephanie , Wollmuth Lonnie P. , Sirotkin Howard I. 
Published: August 2023

ABSTRACTDevelopmental neurogenesis is a tightly regulated spatiotemporal process with its dysregulation implicated in neurodevelopmental disorders. NMDA receptors are glutamate-gated ion channels that are widely expressed in the early nervous system, yet their contribution to neurogenesis is poorly understood. Notably, a variety of mutations in genes encoding NMDA receptor subunits are associated with neurodevelopmental disorders. To rigorously define the role of NMDA receptors in developmental neurogenesis, we used a mutant zebrafish line (grin1-/-) that lacks all NMDA receptors yet survives to 10 days post-fertilization, offering the opportunity to study post-embryonic neurodevelopment in the absence of NMDA receptors. Focusing on the forebrain, we find that these fish have a progressive supernumerary neuron phenotype confined to the telencephalon at the end of embryonic neurogenesis, but which extends to all forebrain regions during postembryonic neurogenesis. This enhanced neuron population does not arise directly from increased numbers or mitotic activity of radial glia cells, the principal neural stem cells. Rather, it stems from a lack of timely maturation of transit-amplifying neuroblasts into post-mitotic neurons, as indicated by a decrease in expression of the ontogenetically-expressed chloride transporter, KCC2. Pharmacological blockade with MK-801 recapitulates thegrin1-/-supernumerary neuron phenotype, indicating a requirement for ionotropic signaling. Thus, NMDA receptors are required for suppression of indirect, transit amplifying cell-driven neurogenesis by promoting maturational termination of mitosis. Loss of suppression results in neuronal overpopulation that can fundamentally change brain circuitry and may be a key factor in pathogenesis of neurodevelopmental disorders caused by NMDA receptor dysfunction.
Estimating the number of breeders from helminth larvae with genomic data
Authors: Dennis Tristan. P. W. , Sands William , Opoku Millicent , Debrah Alex , Batsa Linda , Pfarr Kenneth , Klarmann-Schulz Ute , Hoerauf Achim , Specht Sabine , Scandale Ivan , Ranford-Cartwright Lisa C. , Lamberton Poppy H. L. 
Published: August 2023

AbstractEffective control of helminth infections requires the application of mathematical models to inform control efforts and policy, the development of product profiles for new drugs, and the monitoring of existing drugs for resistance. Key to the success of these approaches is accurately estimating the number of worms within a host, as well as distinguishing, in drug efficacy trials and monitoring, between adults surviving treatment and adults who have reinfected a host following drug treatment. In practice, observing adult worms is often extremely challenging in a patient, as many adult helminths are embedded deep in host tissues. Genetic approaches to infer kinship between larvae or eggs offer a solution to establish adult worm burdens, and to distinguish between treatment failure or treatment success followed by reinfection. Here, we use low-coverage whole-genome, and mitochondrial sequencing, ofOnchocerca volvuluslarvae to estimate the number of adults contributing to pools of offspring of known and unknown parentage. lcWGS reconstructs full-sibling relationships, resolving the number of unique adult worms contributing to a pool of offspring. Mitochondrial genotyping reconstructs maternal sib-ship, thus estimating the minimum number of adult females within a patient. Further development will improve these techniques for evaluating adult worm burden and trial outcome.
Praziquantel activates a native cation current inSchistosoma mansoni
Authors: Chulkov Evgeny G. , Rohr Claudia M. , Marchant Jonathan S. 
Published: August 2023

Praziquantel (PZQ), an anthelmintic drug discovered in the 1970s, is still used to treat schistosomiasis and various other infections caused by parasitic flatworms. PZQ causes a triad of phenotypic effects on schistosome worms – rapid depolarization, muscle contraction, and damage throughout the worm tegument. The molecular target mediating these effects has been intimated as a Ca2+-permeable ion channel, but native currents evoked by PZQ have not been reported in any schistosome cell type. The properties of the endogenous PZQ activated conductance therefore remain unknown. Here, invasive electrophysiology was used to probe for responses to PZQ from different locales in a living schistosome worm. No direct response was seen in tegument-derived vesicles, or from the sub-tegumental muscle layer despite the presence of voltage-operated currents. However, PZQ rapidly triggered a sustained, non-selective cation current in recordings from neuronal tissue, targeting both the anterior ganglion and the main longitudinal nerve cord. The biophysical signature of this PZQ-evoked current resolved at single channel resolution matched that of a transient receptor potential ion channel named TRPMPZQ, recently proposed as the molecular target of PZQ. The endogenous PZQ-evoked current was also inhibited by a validated TRPMPZQantagonist. PZQ therefore is a neuroactive anthelmintic, effecting a robust, depolarization through ion channels with the characteristics of TRPMPZQ.Key Findings / Scope StatementResponses to the anthelmintic drug, praziquantel (PZQ), were examined using invasive electrophysiology in a living schistosome worm.PZQ evoked a cation current in recordings from neuronal tissueThe biophysical and pharmacological characteristics of the native PZQ current matched the properties of TRPMPZQ.
Reengineering of a flavin-binding fluorescent protein using ProteinMPNN
Authors: Nikolaev Andrey , Kuzmin Alexander , Markeeva Elena , Kuznetsova Elizaveta , Semenov Oleg , Anuchina Arina , Remeeva Alina , Gushchin Ivan 
Published: August 2023

AbstractRecent advances in machine learning techniques have led to development of a number of protein design and engineering approaches. One of them, ProteinMPNN, predicts an amino acid sequence that would fold and match user-defined backbone structure. In this short report, we test whether ProteinMPNN can be used to reengineer a flavin-binding fluorescent protein, CagFbFP. We fixed the native backbone conformation and the identity of 20 amino acids interacting with the chromophore (flavin mononucleotide, FMN), while letting ProteinMPNN predict the rest of the sequence. The software package suggested replacing 36-48 out of the remaining 86 amino acids. The three designs that we tested experimentally displayed different expression levels, yet all were able to bind FMN and displayed fluorescence, thermal stability and other properties similar to those of CagFbFP. Our results demonstrate that ProteinMPNN can be used to generate diverging unnatural variants of fluorescent proteins, and, more generally, to reengineer proteins without losing their ligand-binding capabilities.
Border-forming wound repair astrocytes
Authors: O’Shea Timothy M. , Ao Yan , Wang Shinong , Ren Yilong , Cheng Amy , Kawaguchi Riki , Swarup Vivek , Sofroniew Michael V. 
Published: August 2023

AbstractCentral nervous system (CNS) lesions become surrounded by neuroprotective borders of newly proliferated reactive astrocytes. Fundamental features of these cells are poorly understood. Here, we show that 90% of border-forming astrocytes derive from proliferating Aldh1l1-expressing local astrocytes, and 10% from Pdgfra-expressing oligodendrocyte progenitors in mice. Temporal transcriptome analysis, snRNAseq and immunohistochemistry showed that after CNS injury, local mature astrocytes dedifferentiated, proliferated, and became transcriptionally reprogrammed to permanently altered new functional states, with persisting downregulation of molecules associated with astrocyte-neuron interactions, and upregulation of molecules associated with wound healing, microbial defense, and interactions with stromal and immune cells. Our findings show that at CNS injury sites, local mature astrocytes proliferate and adopt canonical features of essential wound repair cells that persist in adaptive states and are the predominant source of neuroprotective borders that re-establish CNS integrity by separating neural parenchyma from stromal and immune cells as occurs throughout the healthy CNS.
4D Single-Particle Tracking with Asynchronous Read-Out SPAD-Array Detector
Authors: Bucci Andrea , Tortarolo Giorgio , Held Marcus Oliver , Bega Luca , Perego Eleonora , Castagnetti Francesco , Bozzoni Irene , Slenders Eli , Vicidomini Giuseppe 
Published: August 2023

AbstractSingle-particle tracking (SPT) techniques are essential for investigating the com-plex functions and interactions of individual, specifically labelled particles in biological environments. Many SPT techniques exist, each optimised towards a different balance between spatiotemporal resolution and range, technical com-plexity, and information content. This bargain is exemplified by the contrast between wide-field camera-based and real-time SPT approaches, with the latter being generally more advanced but at the cost of high complexity. Further-more, the fluorescence lifetime, a powerful tool for investigating the particle’s interactions and nano-environment, has yet to be measured consistently.To overcome these limitations, we propose a novel real-time three-dimensional SPT technique based on a hybrid approach. In our implementation, we equip a confocal laser-scanning microscope with an asynchronous read-out single-photon avalanche diode (SPAD) array detector and few other optics. Each sensitive detector element acts as a confocal pinhole, and the recorded intensity distribu-tion reflects the particle’s position in three dimensions relative to the excitation volume. This localization is used in a real-time feedback system to keep the par-ticle in the centre of the excitation volume. Importantly, as each pixel is an independent single-photon detector, SPT is combined with fluorescence lifetime measurement.Our system achieves a localization precision of up to 30 nm with 100 photons and microsecond time resolution, while also performing fluorescence lifetime mea-surements. First, we validated the technique by tracking fluorescent particles in artificial environments. Secondly, as further validation, we investigated the move-ment of lysosomes in living SK-N-BE cells and measured the fluorescence lifetime of the GFP marker expressed on a membrane protein. We observed an unprece-dented correlation between the changes in fluorescence lifetime and the motion state of the lysosomes.Thanks to its simplicity and the great momentum of confocal microscopy based on SPAD array detector, we expect that this implementation will open to many information-rich correlative imaging and tracking studies.
SNAP-25, but not SNAP-23, is essential for photoreceptor function and survival in mice
Authors: Huang Mengjia , Chow Chun Hin , Gurdita Akshay , Harada Hidekiyo , Pham Truong Victor Q. B. , Eide Sarah , Sun Hong-Shuo , Feng Zhong-Ping , Monnier Philippe P. , Wallace Valerie A. , Sugita Shuzo 
Published: August 2023

AbstractVesicular transport plays critical roles in photopigment delivery at photoreceptor outer segments and glutamate exocytosis at photoreceptor synapses. Previous studies into the role of photoreceptor SNAP proteins are limited in their characterizations into only gene/protein expression and do not delve further into their functional role. Here, we examine the expression and localization of SNAP-23 and SNAP-25 mRNA and protein. Using SNAP-23 and SNAP-25 conditional knockout mice, we further evaluated the morphological and functional consequences that the absence of these proteins has on vision. Although we found that the ubiquitously expressed SNAP-23 showed weak mRNA expression in photoreceptors, removal of SNAP-23 did not result in any observable phenotype. We found that neuronal SNAP-25 is developmentally regulated and SNAP-25 mRNA undergoes mRNA trafficking to the photoreceptor inner segments coinciding with the development of photoreceptor outer segments. Removal of SNAP-25 in photoreceptor cells led to changes in both outer segment protein trafficking and synaptic integrity, resulting in a complete loss of vision in SNAP-25 cKO mice. Our results conclude that SNAP-25, but not SNAP-23, is the essential isoform for photoreceptor survival and function.
Differential cross-reactivity to the influenza B virus haemagglutinin underpins lineage-specific susceptibility between birth cohorts
Authors: Edler Peta , Schwab Lara S.U. , Aban Malet , Wille Michelle , Spirason Natalie , Deng Yi-Mo , Carlock Michael A. , Ross Ted M. , Juno Jennifer A. , Rockman Steve , Wheatley Adam K. , Kent Stephen J. , Barr Ian G. , Price David J. , Koutsakos Marios 
Published: August 2023

AbstractInfluenza exposures early in life are believed to shape future susceptibility to influenza infections by imprinting immunological biases that engender differential cross-reactivity to future influenza viruses, but direct serological evidence linked to susceptibility is limited. We analysed hemagglutination-inhibition titres in 1451 cross-sectional samples collected between 1992-2020, from individuals born between 1917-2008, against influenza B virus (IBV) isolates from 1940-2021, including ‘future’ isolates that circulated after sample collection. We demonstrate that immunological biases are conferred by early life IBV infection and result in lineage-specific cross-reactivity of a birth cohort towards future IBV isolates. This translates into differential estimates of susceptibility between birth cohorts towards the two IBV antigenic lineages, explaining lineage-specific age distributions of observed medically attended IBV infections. Our data bridge a critical gap between early life exposure, cross-reactivity, and influenza epidemiology and identify a plausible model to further dissect the interplay between host immunity, viral evolution and epidemiology.
Von Willebrand Factor Synergizes with Tumor-Derived Extracellular Vesicles to Promote Gastric Cancer Metastasis
Authors: Wang Chen-yu , Wang Min , Cai Wei , Zhao Chan-yuan , Zhou Quan , Zhang Xiao-yu , Wang Feng-xia , Zhang Chen-li , Dang Yun , Yang Ai-jun , Dong Jing-fei , Li Min 
Published: August 2023

ABSTRACTCells of gastric cancer invade local tissue extensively and also metastasize through the circulation to remote organs. Patients with metastasized gastric cancer have poor outcomes. Cancer cells are known to release extracellular vesicles (EVs) that contribute to cancer progression, but how cancer cell-derived EVs promote cancer growth and metastasis remains poorly understood. We have recently reported that levels of circulating gastric cancer cell-derived EVs (gcEVs) and the adhesive ligand von Willebrand factor (VWF) are associated with cancer metastasis and poor prognosis of patients, but the underlying mechanism of this gcEV-VWF interaction was not known. Here we report results from a study designed to investigate the synergistic action of VWF and gcEVs in vitro and in mouse models. We showed that VWF in cancer-bearing mice was hyperadhesive and became microvesicle-bound. EV-bound VWF mediated the adhesion of gcEVs to the endothelium to disrupt endothelial integrity and facilitate the transendothelial migration of cancer cells and pulmonary metastasis. Reducing VWF adhesive activity by the metalloprotease ADAMTS-13 or promoting gcEV clearance by the scavenging factor lactadherin prevented pulmonary metastasis in mice. These results highlight the synergistic action of gcEVs and VWF in promoting gastric cancer metastasis and identifying new targets for its prevention.Key point: Author contributionsHyperadhesive VWF becomes microvesicle-bound to induce endothelial leakage and promote the pulmonary metastasis of gastric cancer in mice.Reducing VWF activity by ADAMTS-13 and accelerating microvesicle clearance by lactadherin reduces pulmonary metastasis of gastric cancer.
Identification of a subpopulation of highly adherent endothelial cells for seeding synthetic vascular grafts
Authors: Wolfe Jayne T. , Chen Vaya , Chen Yiliang , Tefft Brandon J. 
Published: August 2023

AbstractObjectiveThere is an unmet clinical need for a bypass graft that can be used as an alternative to an autologous vessel graft for the treatment of severe coronary artery disease. Small-diameter (<6mm) synthetic vascular grafts are not suitable because of unacceptable patency rates. This mainly occurs without an endothelial cell (EC) monolayer to prevent platelet activation, thrombosis, and intimal hyperplasia. While numerous studies have explored methods to improve EC adhesion to biomaterials, there are still no reliable methods to endothelialize small-diameter grafts, as most seeded ECs are lost due to exposure to fluid shear stress (SS) after implantation. The goal of this work is to determine if EC loss is a random process or if it is possible to predict which cells are more likely to remain adherent.Approach and ResultsIn initial studies, we sorted ECs using fluid SS and identified a subpopulation of ECs that are more likely to resist detachment. We use RNA-sequencing (RNA-seq) to examine gene expression of adherent ECs compared to the whole population to identify targets for improving adhesion. Fibronectin leucine rich transmembrane protein 2 (FLRT2), which encodes protein FLRT2, emerged as a candidate due to its downregulation in the adherent ECs and known role in cell adhesion. Using fluorescence activated cell sorting (FACS), we sorted ECs based on FLRT2 expression levels and demonstrated that ECs expressing low levels of FLRT2 exhibit greater retention under fluid SS in vitro.ConclusionFor the first time, we show EC detachment is not an entirely random process and we predicted which ECs were more likely to remain adherent on a vascular graft upon exposure to fluid SS. This provides validation for the concept that we can seed a small-diameter vascular graft only with highly adherent ECs to maintain a stable endothelium and improve graft patency rates.Non-standard Abbreviations and Acronymsendothelial cell (EC), shear stress (SS), fibronectin leucine rich transmembrane protein 2 (FLRT2), tissue engineered vascular graft (TEVG), fluorescence activated cell sorting (FACS)
Timing of methamphetamine exposure during adolescence differentially influences parvalbumin and perineuronal net immunoreactivity in the medial prefrontal cortex of female, but not male, rats
Authors: Brinks Amara S. , Carrica Lauren K. , Tagler Dominic J. , Gulley Joshua M. , Juraska Janice M. 
Published: August 2023

AbstractAdolescence involves significant reorganization within the medial prefrontal cortex (mPFC), including modifications to inhibitory neurotransmission mediated through parvalbumin (PV) interneurons and their surrounding perineuronal nets (PNNs). These developmental changes, which result in increased PV neuron activity in adulthood, may be disrupted by drug use resulting in lasting changes in mPFC function and behavior. Methamphetamine (METH), which is a readily available drug used by some adolescents, increases PV neuron activity and could influence the activity-dependent maturational process of these neurons. In the present study, we used male and female Sprague Dawley rats to test the hypothesis that METH exposure influences PV and PNN expression in a sex- and age-specific manner. Rats were injected daily with saline or 3.0 mg/kg METH from early adolescence (EA; 30-38 days old), late adolescence (LA; 40-48 days old), or young adulthood (60-68 days old). One day following exposure, effects of METH on PV cell and PNN expression were assessed using immunofluorescent labeling within the mPFC. METH exposure did not alter male PV neurons or PNNs. Females exposed in early adolescence or adulthood had more PV expressing neurons while those exposed in later adolescence had fewer, suggesting distinct windows of vulnerability to changes induced by METH exposure. In addition, females exposed to METH had more PNNs and more intense PV neuron staining, further suggesting that METH exposure in adolescence uniquely influences development of inhibitory circuits in the female mPFC. This study indicates that the timing of METH exposure, even within adolescence, influences its neural effects in females.