bluuebunny/crossref_metadata_2025_split huggingface dataset:
NK cell-induced damage toP.falciparum-infected erythrocytes requires ligand-specific recognition and releases parasitophorous vacuoles that are phagocytosed by monocytes in the presence of immune IgG
Authors: Sekar Padmapriya , Rajagopalan Sumati , Shabani Estela , Kanjee Usheer , Schureck Marc A. , Arora Gunjan , Peterson Mary E. , Traore Boubacar , Crompton Peter D. , Duraisingh Manoj T. , Desai Sanjay A. , Long Eric O. 
Published: August 2023

AbstractNatural killer (NK) cells lyse virus-infected cells and transformed cells through polarized delivery of lytic effector molecules into target cells. We have shown that NK cells lysePlasmodium falciparum-infected red blood cells (iRBC) via antibody-dependent cellular cytotoxicity (ADCC). A high frequency of adaptive NK cells, with elevated intrinsic ADCC activity, in people chronically exposed to malaria transmission is associated with reduced parasitemia and resistance to disease. How NK cells bind to iRBC and the outcome of iRBC lysis by NK cells has not been investigated. We applied gene ablation in inducible erythrocyte precursors and antibody-blocking experiments with iRBC to demonstrate a central role of CD58 and ICAM-4 as ligands for adhesion by NK cells via CD2 and integrin αMβ2, respectively. Adhesion was dependent on opsonization of iRBC by IgG. Live imaging and quantitative flow cytometry of NK-mediated ADCC toward iRBC revealed that damage to the iRBC plasma membrane preceded damage toP. falciparumwithin parasitophorous vacuoles (PV). PV were identified and tracked with aP.falciparumstrain that expresses the PV membrane-associated protein EXP2 tagged with GFP. After NK-mediated ADCC, PV were either found inside iRBC ghosts or released intact and devoid of RBC plasma membrane. Electron microscopy images of ADCC cultures revealed tight NK–iRBC synapses and free GFP+vesicles similar to GFP+PV isolated from iRBC lysates by cell sorting. The titer of IgG in plasma of malaria-exposed individuals that bound PV was two orders of magnitude higher than IgG that bound iRBC. This immune IgG stimulated efficient phagocytosis of PV by primary monocytes. The selective NK-mediated damage to iRBC, resulting in release of PV, and subsequent phagocytosis of PV by monocytes may combine for efficient killing and removal of intra-erythrocyticP.falciparumparasite. This mechanism may mitigate the inflammation and malaria symptoms during blood-stageP. falciparuminfection.
Assessing the impact of binary land cover variables on species distribution models: A North American study on water birds
Authors: Gabor Lukas , Cohen Jeremy , Jetz Walter 
Published: August 2023

AbstractAimSpecies distribution models (SDMs) are an important tool for predicting species occurrences in geographic space and for understanding the drivers of these occurrences. An effect of environmental variable selection on SDM outcomes has been noted, but how the treatment of variables influences models, including model performance and predicted range area, remains largely unclear. For example, although landcover variables included in SDMs in the form of proportions, or relative cover, recent findings suggest that for species associated with uncommon habitats the simple presence or absence of a landcover feature is most informative. Here we investigate the generality of this hypothesis and determine which representation of environmental features produces the best-performing models and how this affects range area estimates. Finally, we document how outcomes are modulated by spatial grain size, which is known to influence model performance and estimated range area.LocationNorth AmericaMethodsWe fit species distribution models (via Random Forest) for 57 water bird species using proportional and binary estimates of water cover in a grid cell using occurrence data from the eBird citizen science initiative. We evaluated four different thresholds of feature prevalence (land cover representations) within the cell (1%, 10%, 20% or 50%) and fit models across both breeding and non-breeding seasons and multiple grain sizes (1, 5, 10, and 50 km cell lengths).ResultsModel performance was not significantly affected by the type of land cover representation. However, when the models were fitted using binary variables, the model-assessed importance of water bodies significantly decreased, especially at coarse grain sizes. In this binary variable-case, models relied more on other land cover variables, and over-or under-predicted the species range by 5-30%. In some cases, differences up to 70% in predicted species ranges were observed.Main conclusionsMethods for summarizing landcover features are often an afterthought in species distribution modelling. Inaccurate range areas resulting from treatment of landcover features as binary or proportional could lead to the prioritization of conservation efforts in areas where the species do not occur or cause the importance of crucial habitats to be missed. Importantly, our results suggest that at finer grain sizes, binary variables might be more useful for accurately measuring species distributions. For studies using relatively coarse grain sizes, we recommend fitting models with proportional land cover variables.
Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer
Authors: Langer Henning Tim , Ramsamooj Shakti , Dantas Ezequiel , Murthy Anirudh , Ahmed Mujmmail , Hwang Seo-Kyoung , Grover Rahul , Pozovskiy Rita , Liang Roger J. , Queiroz Andre Lima , Brown Justin C , White Eileen P. , Janowitz Tobias , Goncalves Marcus D. 
Published: August 2023

AbstractThe cancer associated cachexia syndrome (CACS) is a systemic metabolic disorder resulting in loss of body weight due to skeletal muscle and adipose tissues atrophy. CACS is particularly prominent in lung cancer patients, where it contributes to poor quality of life and excess mortality. Using the Kras/Lkb1 (KL) mouse model, we found that CACS is associated with white adipose tissue (WAT) dysfunction that directly affects skeletal muscle homeostasis. WAT transcriptomes showed evidence of reduced adipogenesis, and, in agreement, we found low levels of circulating adiponectin. To preserve adipogenesis and restore adiponectin levels, we treated mice with the PPAR-γ agonist, rosiglitazone. Rosiglitazone treatment increased serum adiponectin levels, delayed weight loss, and preserved skeletal muscle and adipose tissue mass, as compared to vehicle-treated mice. The preservation of muscle mass with rosiglitazone was associated with increases in AMPK and AKT activity. Similarly, activation of the adiponectin receptors in muscle cells increased AMPK activity, anabolic signaling, and protein synthesis. Our data suggest that PPAR-γ agonists may be a useful adjuvant therapy to preserve tissue mass in lung cancer.Key points- The PPAR-γ agonist, rosiglitazone, restores circulating adiponectin levels in mice with lung cancer.- Rosiglitazone preserves skeletal muscle and adipose tissue mass in mice with lung cancer.- The preservation of muscle mass with rosiglitazone is associated with increases in AMPK and AKT activity.- Stimulation of adiponectin signaling increases AMPK activity, anabolic signaling, and protein synthesis in muscle cell culture.
Electrical Brain Activity during Human Walking with Parametric Variations in Terrain Unevenness and Walking Speed
Authors: Liu Chang , Downey Ryan J. , Salminen Jacob S. , Rojas Sofia Arvelo , Richer Natalie , Pliner Erika M. , Hwang Jungyun , Cruz-Almeida Yenisel , Manini Todd M. , Hass Chris J. , Seidler Rachael D. , Clark David J. , Ferris Daniel P. 
Published: August 2023

AbstractMobile brain imaging with high-density electroencephalography (EEG) can provide insight into the cortical processes involved in complex human walking tasks. While uneven terrain is common in the natural environment and poses challenges to human balance control, there is limited understanding of the supraspinal processes involved with traversing uneven terrain. The primary objective of this study was to quantify electrocortical activity related to parametric variations in terrain unevenness for neurotypical young adults. We used high-density EEG to measure brain activity when thirty-two young adults walked on a novel custom-made uneven terrain treadmill surface with four levels of difficulty at a walking speed tailored to each participant. We identified multiple brain regions associated with uneven terrain walking. Alpha (8 - 13 Hz) and beta (13 - 30 Hz) spectral power decreased in the sensorimotor and posterior parietal areas with increasing terrain unevenness while theta (4 - 8 Hz) power increased in the mid/posterior cingulate area with terrain unevenness. We also found that within stride spectral power fluctuations increased with terrain unevenness. Our secondary goal was to investigate the effect of parametric changes in walking speed (0.25 m/s, 0.5m/s, 0.75 m/s, 1.0 m/s) to differentiate the effects of walking speed from uneven terrain. Our results revealed that electrocortical activities only changed substantially with speed within the sensorimotor area but not in other brain areas. Together, these results indicate there are distinct cortical processes contributing to the control of walking over uneven terrain versus modulation of walking speed on smooth, flat terrain. Our findings increase our understanding of cortical involvement in an ecologically valid walking task and could serve as a benchmark for identifying deficits in cortical dynamics that occur in people with mobility deficits.
The Interferon γ Pathway Enhances Pluripotency and X-Chromosome Reactivation in iPSC reprogramming
Authors: Barrero Mercedes , López-Rubio Anna V. , Lazarenkov Aleksey , Blanco Enrique , Bauer Moritz , Palma Luis G. , Bigas Anna , Di Croce Luciano , Sardina José Luis , Payer Bernhard 
Published: August 2023

AbstractReprogramming somatic cells into induced pluripotent stem cells (iPSCs) requires activation of the pluripotency network and resetting of the epigenome by erasing the epigenetic memory of the somatic state. In female mouse cells, a critical epigenetic reprogramming step is the reactivation of the inactive X chromosome. Despite its importance, a systematic understanding of the regulatory networks linking pluripotency and X-reactivation is missing. Here we reveal the pathways important for iPSC reprogramming and X-reactivation using a genome-wide CRISPR screen. In particular, we discover that activation of the interferon γ (IFNγ) pathway early during reprogramming accelerates pluripotency acquisition and X-reactivation. IFNγ stimulates STAT3 signaling and the pluripotency network and leads to enhanced TET-mediated DNA demethylation, which consequently boosts X-reactivation. We therefore gain a mechanistic understanding of the role of IFNγ in reprogramming and X-reactivation and provide a comprehensive resource of the molecular networks involved in these processes.
Detection of prions from spiked and free-ranging carnivore feces
Authors: Inzalaco H. N. , Brandell E. E. , Wilson S.P. , Hunsaker M. , Stahler D. R. , Woelfel K. , Walsh D. P. , Nordeen T. , Storm D. J. , Lichtenberg S. S. , Turner W. C. 
Published: August 2023

ABSTRACTChronic wasting disease (CWD) is a highly contagious, fatal neurodegenerative disease caused by infectious prions (PrPCWD) affecting wild and captive cervids. Although experimental feeding studies have demonstrated prions in feces of crows (Corvus brachyrhynchos), coyotes (Canis latrans), and cougars (Puma concolor), the role of scavengers and predators in CWD epidemiology remains poorly understood. Here we applied the real-time quaking-induced conversion (RT-QuIC) assay to detect PrPCWDin feces from cervid consumers, to advance surveillance approaches, which could be used to improve disease research and adaptive management of CWD. We assessed recovery and detection of PrPCWDby experimental spiking of PrPCWDinto carnivore feces from 9 species sourced from CWD-free populations or captive facilities. We then applied this technique to detect PrPCWDfrom feces of predators and scavengers in free-ranging populations. Our results demonstrate that spiked PrPCWDis detectable from feces of free-ranging mammalian and avian carnivores using RT-QuIC. Results show that PrPCWDacquired in natural settings is detectable in feces from free-ranging carnivores, and that PrPCWDrates of detection in carnivore feces reflect relative prevalence estimates observed in the corresponding cervid populations. This study adapts an important diagnostic tool for CWD, allowing investigation of the epidemiology of CWD at the community-level.
Genomic DNA extraction optimization and validation for genome sequencing using the marine gastropod Kellet’s whelk
Authors: Daniels Benjamin N , Nurge Jenna , Sleeper Olivia , Lee Andy , López Cataixa , Christie Mark , Toonen Robert J , Davidson Jean , White Crow 
Published: August 2023

ABSTRACTNext-generation sequencing technologies, such as Nanopore MinION, Illumina Hiseq and Novaseq, and PacBio Sequel II, hold immense potential for advancing genomic research on non-model organisms, including the vast majority of marine species. However, application of these technologies to marine invertebrate species is often impeded by challenges in extracting and purifying their genomic DNA due to high polysaccharide content and other secondary metabolites. In this study, we help resolve this issue by developing and testing DNA extraction protocols for Kellet’s whelk (Kelletia kelletii), a subtidal gastropod with ecological and commercial importance, by comparing four DNA extraction methods commonly used in marine invertebrate studies. We identified an optimized protocol that balances efficiency, cost, and DNA extraction quality; the Salting out protocol. We validated the protocol using an independent set of tissue samples, then applied it to extract high-molecular-weight (HMW) DNA from over three thousand Kellet’s whelk tissue samples. The protocol demonstrated scalability and, with added clean-up, suitability for RAD-seq, GT-seq, as well as whole genome sequencing using both long read (ONT MinION) and short read (Illumina Novaseq) sequencing platforms. Our findings offer a robust and versatile DNA extraction and clean-up protocol for supporting genomic research efforts on non-model marine organisms, to help mediate the under-representation of invertebrates in genomic studies.
Multiomics responses to seasonal variations in diel cycles in the marine phytoplanktonic picoeukaryoteOstreococcus tauri
Authors: Romero-Losada Ana B. , Arvanitidou Christina , García-Gómez M. Elena , Morales-Pineda María , Castro-Pérez M. José , García-González Mercedes , Romero-Campero Francisco J. 
Published: August 2023

AbstractEarth tilted rotation and translation around the Sun produce one of the most pervasive periodic environmental signals on our planet giving rise to seasonal variations in diel cycles. Although marine phytoplankton plays a key role on ecosystems and present promising biotechnological applications, multiomics integrative analysis of their response to these rhythms remains largely unexplored. We have chosen the marine picoeukaryoteOstreococcus taurias model organism grown under summer long days, winter short days, constant light and constant dark conditions to characterize these responses in marine phytoplankton. Although 80% of the transcriptome present diel rhythmicity under both seasonal conditions less than 5% maintained oscillations under all constant conditions. A drastic reduction in protein abundance rhythmicity was observed with 55% of the proteome oscillating. Seasonally specific rhythms were found in key physiological processes such as cell cycle progression, photosynthetic efficiency, carotenoid content, starch accumulation and nitrogen assimilation. A global orchestration between transcriptome, proteome and physiological dynamics was observed with specific seasonal temporal offsets between transcript, protein and physiological peaks.
Effects of 4 testing arena sizes and 11 types of embryo media on sensorimotor behaviors in wild-type andchd7mutant zebrafish larvae
Authors: Hodorovich Dana R. , Harris Tiara Fryer , Burton Derek , Neese Katie , Bieler Rachael , Chudasama Vimal , Marsden Kurt. C 
Published: August 2023

AbstractThe larval zebrafish is a highly versatile model across research disciplines, and the expanding use of behavioral analysis has contributed to many advances in neuro-psychiatric, developmental, and toxicological studies, often through large-scale chemical and genetic screens. In the absence of standardized approaches to larval zebrafish behavior analysis, however, it is critical to understand the impact on behavior of experimental variables such as the size of testing arenas and the choice of embryo medium. Using a custom-built, modular high-throughput testing system, we examined the effects of 4 testing arena sizes and 11 types of embryo media on conserved sensorimotor behaviors in zebrafish larvae. Our data show that testing arena size impacts acoustic startle sensitivity and kinematics as well as spontaneous locomotion and thigmotaxis, with fish tested in larger arenas displaying reduced startle sensitivity and increased locomotion. We also find that embryo media can dramatically affect startle sensitivity, kinematics, habituation, and pre-pulse inhibition, as well as spontaneous swimming, turning, and overall activity. Common media components such as methylene blue and high calcium concentration consistently reduced startle sensitivity and locomotion. To further address how the choice of embryo medium can impact phenotype expression in zebrafish models of disease, we rearedchd7mutant larvae, a model of CHARGE syndrome with previously characterized morphological and behavioral phenotypes, in 5 different types of media and observed impacts on all phenotypes. By defining the effects of these key extrinsic factors on larval zebrafish behavior, these data can help researchers select the most appropriate conditions for their specific research questions, particularly for genetic and chemical screens.
Integrated Organ Immunity: Antigen-specific CD4-T cell-derived IFN-γ induced by BCG imprints prolonged lung innate resistance against respiratory viruses
Authors: Lee Audrey , Floyd Katharine , Wu Shengyang , Fang Zhuoqing , Tan Tze Kai , Li Chunfeng , Hui Harold , Scoville David , Ruggiero Alistaire D. , Liang Yan , Pavenko Anna , Lujan Victor , Nolan Garry P. , Arunachalam Prabhu , Suthar Mehul , Pulendran Bali 
Published: August 2023

ABSTRACTBacille Calmette-Guérin (BCG) vaccination can confer non-specific protection against heterologous pathogens. However, the underlying mechanisms remain mysterious. Here, we show that mice immunized intravenously with BCG exhibited reduced weight loss and/or improved viral clearance when challenged with SARS-CoV-2 and influenza. Protection was first evident between 14 - 21 days post vaccination, and lasted for at least 42 days. Remarkably, BCG induced a biphasic innate response in the lung, initially at day 1 and a subsequent prolonged phase starting at ∼15 days post vaccination, and robust antigen-specific Th1 responses. MyD88-dependent TLR signaling was essential for the induction of the innate and Th1 responses, and protection against SARS-CoV-2. Depletion of CD4+T cells or IFN-γ activity prior to infection obliterated innate activation and protection. Single cell and spatial transcriptomics revealed CD4-dependent expression of interferon-stimulated genes (ISGs) in myeloid, type II alveolar and lung epithelial cells. Thus, BCG elicits “integrated organ immunity” where CD4+ T cells act on local myeloid and epithelial cells to imprint prolonged antiviral innate resistance.
Effect of diffusivity of amyloid beta monomers on the formation of senile plaques
Authors: Kuznetsov Andrey V. 
Published: August 2023

AbstractAlzheimer’s disease (AD) presents a perplexing question: why does its development span decades, even though individual amyloid beta (Aβ) deposits (senile plaques) can form rapidly in as little as 24 hours, as recent publications suggest? This study investigated whether the formation of senile plaques can be limited by factors other than polymerization kinetics alone. Instead, their formation may be limited by the diffusion-driven supply of Aβ monomers, along with the rate at which the monomers are produced from amyloid precursor protein (APP) and the rate at which Aβ monomers undergo degradation. A mathematical model incorporating the nucleation and autocatalytic process (via the Finke-Watzky model), as well as Aβ monomer diffusion, was proposed. The obtained system of partial differential equations was solved numerically, and a simplified version was investigated analytically. The computational results predicted that it takes approximately 7 years for Aβ aggregates to reach a neurotoxic concentration of 50 μM. Additionally, a sensitivity analysis was performed to examine how the diffusivity of Aβ monomers and their production rate impact the concentration of Aβ aggregates.
Genomic analysis supports Cape Lion population connectivity prior to colonial eradication and extinction
Authors: de Flamingh A. , Gnoske T.P. , Rivera-Colón A.G. , Simeonovski V.A. , Kerbis Peterhans J.C. , Yamaguchi N. , Witt K.E. , Catchen J. , Roca A.L. , Malhi R.S. 
Published: August 2023

AbstractExtinct Cape lions (Panthera leo melanochaitus) formerly ranged throughout the grassland plains of the “Cape Flats” in what is today known as the Western Cape Province, South Africa. Cape lions were likely eradicated because of overhunting and habitat loss after European colonization. European naturalists originally described Cape lions as “Black-maned lions” and claimed that they were phenotypically distinct. However, other depictions and historical descriptions of lions from the Cape report mixed or light coloration and without black or extensively developed manes. These findings suggest that, rather than forming a distinct population, Cape lions may have had phenotypic and genotypic variation similar to other African lions. Here we investigate extinct Cape lion genome characteristics, population dynamics and genetic distinctiveness prior to their extinction. We generated genomic data from two historic Cape lions to compare to 118 existing high-coverage mitogenomes, and low-coverage nuclear genomes of 53 lions from 13 African countries. We show that, before their eradication, lions from the Cape Flats had diverse mitogenomes and nuclear genomes that clustered with lions from both southern and eastern Africa. Cape lions had high genome-wide heterozygosity and low inbreeding coefficients, indicating that populations in the Cape Flats went extinct so rapidly that genomic effects associated with long-term small population size and isolation were not detectable. Our findings do not support the characterization of Cape lions as phylogeographically distinct, as originally put forth by some European naturalists, but rather highlights how alternative knowledge-systems, e.g., Indigenous perspectives, could potentially further inform interpretations of species’ life histories.