bluuebunny/crossref_metadata_2025_split huggingface dataset:
A translation proofreader of archaeal origin imparts multialdehyde stress tolerance to land plants
Authors: Kumar Pradeep , Roy Ankit , Mukul Shivapura Jagadeesha , Singh Avinash Kumar , Singh Dipesh Kumar , Nalli Aswan , Banerjee Pujaita , Babu Kandhalu Sagadevan Dinesh , Raman Bakthisaran , Kruparani Shobha P. , Siddiqi Imran , Sankaranarayanan Rajan 
Published: October 2023

AbstractAldehydes, being an integral part of carbon metabolism, energy generation and signalling pathways, are ingrained in plant physiology. Land plants have developed intricate metabolic pathways which involve production of reactive aldehydes and its detoxification to survive harsh terrestrial environments. Here, we show that physiologically produced aldehydes i.e., formaldehyde and methylglyoxal in addition to acetaldehyde, generate adducts with aminoacyl-tRNAs, a substrate for protein synthesis. Plants are unique in possessing two distinct chiral proofreading systems, D-aminoacyl-tRNA deacylase1 (DTD1) and DTD2, of bacterial and archaeal origins, respectively. Extensive biochemical analysis revealed that only archaeal DTD2 can remove the stable D-aminoacyl adducts on tRNA thereby shielding archaea and plants from these system-generated aldehydes. Using Arabidopsis as a model system, we have shown that the loss of DTD2 gene renders plants susceptible to these toxic aldehydes as they generate stable alkyl modification on D-aminoacyl-tRNAs, which are recycled only by DTD2. Bioinformatic analysis identifies the expansion of aldehyde metabolising repertoire in land plant ancestors which strongly correlates with the recruitment of archaeal DTD2. Finally, we demonstrate that the overexpression of DTD2 offers better protection against aldehydes than in wild-type Arabidopsis highlighting its role as a multi-aldehyde detoxifier that can be explored as a transgenic crop development strategy.
Depletion of SMN Protein in Mesenchymal Progenitors Impairs the Development of Bone and Neuromuscular Junction in Spinal Muscular Atrophy
Authors: Hann Sang-Hyeon , Kim Seon-Yong , Kim Ye Lynne , Jo Young-Woo , Kang Jong-Seol , Park Hyerim , Choi Se-Young , Kong Young-Yun 
Published: October 2023

AbstractSpinal Muscular Atrophy (SMA) is a neuromuscular disorder characterized by the deficiency of the survival motor neuron (SMN) protein, which leads to motor neuron dysfunction and muscle atrophy. In addition to the requirement for SMN in motor neurons, recent studies suggest that SMN deficiency in peripheral tissues plays a key role in the pathogenesis of SMA. Using limb mesenchymal progenitor cells (MPCs)-specific SMN-depleted mouse models, we reveal that SMN reduction in chondrocytes and fibro-adipogenic progenitors (FAPs) derived from limb MPCs causes defects in the development of bone and neuromuscular junction (NMJ), respectively. We showed that impaired growth plate homeostasis, which causes skeletal growth defects in SMA, is due to reduced IGF signaling from chondrocytes rather than the liver. Furthermore, the reduction of SMN in FAPs resulted in abnormal NMJ maturation, altered release of neurotransmitters, and NMJ morphological defects. Transplantation of healthy FAPs rescued the morphological deterioration. Our findings highlight the significance of mesenchymal SMN in neuromusculoskeletal pathogenesis in SMA and provide insights into potential therapeutic strategies targeting mesenchymal cells for the treatment of SMA.
Delivery of A Jagged1-PEG-MAL hydrogel with Pediatric Human Bone Cells Regenerates Critically-Sized Craniofacial Bone Defects
Authors: Kamalakar Archana , Tobin Brendan , Kaimari Sundus , Robinson M. Hope , Toma Afra I. , Cha Timothy , Chihab Samir , Moriarity Irica , Gautam Surabhi , Bhattaram Pallavi , Abramowicz Shelly , Drissi Hicham , García Andrés J. , Wood Levi B. , Goudy Steven L. 
Published: October 2023

AbstractTreatments for congenital and acquired craniofacial (CF) bone abnormalities are limited and expensive. Current reconstructive methods include surgical correction of injuries, short-term bone stabilization, and long-term use of bone grafting solutions, including implantation of (i) allografts which are prone to implant failure or infection, (ii) autografts which are limited in supply. Current bone regenerative approaches have consistently relied on BMP2 application with or without addition of stem cells. BMP2 treatment can lead to severe bony overgrowth or uncontrolled inflammation, which can accelerate further bone loss. Bone marrow-derived mesenchymal stem cell-based treatments, which do not have the side effects of BMP2, are not currently FDA approved, and are time and resource intensive. There is a critical need for novel bone regenerative therapies to treat CF bone loss that have minimal side effects, are easily available, and are affordable. In this study we investigated novel bone regenerative therapies downstream of JAGGED1 (JAG1).We previously demonstrated that JAG1 induces murine cranial neural crest (CNC) cells towards osteoblast commitment via a NOTCH non-canonical pathway involving JAK2-STAT5 (1) and that JAG1 delivery with CNC cells elicits bone regeneration in vivo. In this study, we hypothesize that delivery of JAG1 and induction of its downstream NOTCH non-canonical signaling inpediatric human osteoblastsconstitute an effective bone regenerative treatment in an in vivo murine bone loss model of a critically-sized cranial defect. Using this CF defect model in vivo, we delivered JAG1 with pediatric human bone-derived osteoblast-like (HBO) cells to demonstrate the osteo-inductive properties of JAG1 in human cells and in vitro we utilized the HBO cells to identify the downstream non-canonical JAG1 signaling intermediates as effective bone regenerative treatments. In vitro, we identified an important mechanism by which JAG1 induces pediatric osteoblast commitment and bone formation involving the phosphorylation of p70 S6K. This discovery enables potential new treatment avenues involving the delivery of tethered JAG1 and the downstream activators of p70 S6K as powerful bone regenerative therapies in pediatric CF bone loss.
Simulating atmospheric drought: Silica gel packets dehumidify mesocosm microclimates
Authors: Varghese S. , Aguirre B.A. , Isbell F. , Wright A.J. 
Published: October 2023

AbstractAs global temperatures rise, droughts are becoming more frequent and severe. To predict how drought might affect plant communities, ecologists have traditionally designed experiments with controlled watering regimes and rainout shelters. Both treatments have proven effective for simulating soil drought. However, neither are designed to directly modify atmospheric drought.Here, we detail the efficacy of a silica gel atmospheric drought treatment in outdoor mesocosms with and without a cooccurring soil drought treatment. At California State University, Los Angeles, we monitored relative humidity (RH), temperature, and vapor pressure deficit (VPD) every 10 minutes for five months in a bare-ground experiment featuring mesocosms treated with soil drought (reduced watering) and/or atmospheric drought (silica packets suspended 12 cm above soil).We found that silica packets dehumidified these microclimates most effectively (-5% RH) when combined with reduced soil water, regardless of the ambient humidity levels of the surrounding air. Further, packets increased microclimate VPD most effectively (+0.4 kPa) when combined with reduced soil water and ambient air temperatures above 20°C. Finally, packets simulated atmospheric drought most consistently when replaced within three days of deployment.Our results demonstrate the use of silica packets as effective dehumidification agents in outdoor drought experiments. We emphasize that incorporating atmospheric drought in existing soil drought experiments can improve our understandings of the ecological impacts of drought.
Diet and chemical defenses of the Sonoran Desert toads
Authors: Luccioni Marina D. , Wyman Jules T. , Espinoza Edgard O. , O’Connell Lauren A. 
Published: October 2023

AbstractThe Sonoran Desert Toad (Incilius alvarius) is the only animal known to secrete the psychedelic compound 5-MeO-DMT as a chemical defense, but the source of 5-MeO-DMT inI. alvariusremains unknown. Some amphibians endogenously produce chemical defenses while others acquire them from specialized diets. In this study we analyzed toxin gland secretions and diet profiles from wildI. alvariusand sympatric anurans from native and urban habitats around Tucson, Arizona to explore possible links between diet and 5-MeO-DMT production. AllI. alvariussecreted high concentrations of 5-MeO-DMT, whereas other sympatric toads did not. The diet ofI. alvariuswas similar to that of sympatric anurans, indicating thatI. alvariusdoes not exhibit relative dietary specialization. Slight dietary differences betweenI. alvariusin native and urbanized habitats were observed. Taken together, these lines of evidence suggest that diet is not directly linked to 5-MeO-DMT production, and support the alternative hypotheses that Sonoran Desert toads synthesize 5-MeO-DMT endogenously or via a microbial symbiont.
Mouse Model of Heart Attack and Stroke Shows Improved Survival with MPO Inhibition
Authors: Shamsuzzaman Sohel , Deaton Rebecca A. , Doviak Heather , Evans Megan A. , Salamon Anita , Karnewar Santosh , Serbulea Vlad , Alencar Gabriel F. , Shankman Laura S. , Walsh Kenneth , Bekiranov Stefan , Kocher Olivier , Krieger Monty , Kull Bengt , Persson Marie , Bergenhem Nils , Heydarkhan-Hagvall Sepideh , Owens Gary K. 
Published: October 2023

AbstractThromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide1. Unfortunately, the lack of a mouse model that develops advanced coronary atherosclerosis and that exhibits a high incidence of spontaneous plaque rupture with MI or stroke has greatly stymied development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Herein, we describe a novel mouse model that develops widespread advanced atherosclerosis including in coronary, brachiocephalic, and carotid arteries. These mice show high mortality following Western Diet feeding with clear evidence of plaque rupture, MI, and stroke. To validate the utility of this model, mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme primarily produced by activated neutrophils and predictive of rupture of human atherosclerotic lesions2–7. AZM198 treatment resulted in marked improvements in survival with a greater than 60% decrease in the incidence of plaque rupture, MI, and stroke. In summary, our work describes a novel mouse model that closely replicates late-stage clinical events of advanced human atherosclerotic disease and evidence that this model can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.
Unifying microorganisms and macrograzers in rocky shore ecological networks
Authors: Arboleda-Baena Clara , Pareja Claudia Belén , Poblete Javiera , Berlow Eric , Sarmento Hugo , Logares Ramiro , De la Iglesia Rodrigo , Navarrete Sergio A. 
Published: October 2023

ABSTRACTOver the past decades, our understanding of the vital role microbes play in ecosystem processes has greatly expanded. However, we still have limited knowledge about how microbial communities interact with larger organisms. Many existing representations of microbial interactions are based on co-occurrence patterns, which do not provide clear insights into trophic or non-trophic relationships. In this study, we untangled trophic and non-trophic interactions between macroscopic and microscopic organisms on a marine rocky shore. Five abundant mollusk grazers were selected, and their consumptive (grazing) and non-consumptive (grazer pedal mucus) interactions with bacteria in biofilms were measured using 16S rRNA amplicon sequencing. While no significant effects on a commonly used measure of biofilm grazing (Chlorophyll-a concentration) were observed, detailed image analysis revealed that all grazers had a detrimental impact on biofilm cover. Moreover, different grazers exhibited distinct effects on various bacterial groups. Some groups, such as Rhodobacteraceae, Saprospiraceae, Flavobacteriaceae, and Halieaceae, experienced positive effects from specific grazers, while others, like Rhizobiaceae, Rhodobacteraceae, and Flavobacteriaceae were negatively affected by certain grazers. This study presents the first attempt to construct an interaction network between macroorganisms and bacteria. It demonstrates that the strength of trophic and non-trophic interactions varies significantly depending on the mollusk grazer or bacterial group involved. Notably, certain bacterial groups exhibited a generalized response, while others showed specialized responses to specific macroorganisms in trophic or non-trophic interactions. Overall, this work highlights the potential for integrating microbes into ecological networks, providing valuable insights and methodologies for quantifying interactions across Domains. This research complements the previous ecological network, showing that mollusk grazers interact not only trophically but also non-trophically with epilithic biofilms. It identifies three drivers affecting microbial community assembly, crucial for understanding macro-microorganism dynamics in intertidal systems.
Isolating structured salient variations in single-cell transcriptomic data with StrastiveVI
Authors: Qiu Wei , Weinberger Ethan , Lee Su-In 
Published: October 2023

AbstractSingle-cell RNA sequencing (scRNA-seq) has provided deeper insights into biological processes by highlighting differences at the cellular level. Within these single-cell omics measurements, researchers are often interested in identifying variations associated with a specific covariate. For instance, in aging research, it becomes vital to differentiate variations related to aging. To address this, we introduce StrastiveVI (Structured Contrastive Variational Inference;https://github.com/suinleelab/StrastiveVI), which effectively separates the variations of interest from other dominant biological signals in scRNA-seq datasets. When deployed on aging and Alzheimer’s disease (AD) datasets, StrastiveVI efficiently isolates aging and AD-associated patterns, distinguishing them from dominant variations linked to sex, tissue, and cell type that are unrelated to aging or AD. In doing so, it underscores both well-known genes and potential novel genes related to aging or AD.
Modulation of Calcium Signaling and Metabolic Pathways in Endothelial Cells with Magnetic Fields
Authors: Gorobets Oksana , Gorobets Svitlana , Polyakova Tatyana , Zablotskii Vitalii 
Published: October 2023

AbstractCalcium signaling plays a crucial role in various physiological processes, including muscle contraction, cell division, and neurotransmitter release. Dysregulation of calcium levels and signaling has been linked to a range of pathological conditions such as neurodegenerative disorders, cardiovascular disease, and cancer. Here, we suggest that in the endothelium, calcium ion channel activity and calcium signaling can be modulated by applying either a time-varying or static gradient magnetic field (MF). This modulation is achieved by exerting magnetic forces or torques on either biogenic or non-biogenic magnetic nanoparticles that are bound to endothelial cell membranes. Since calcium signaling in endothelial cells induces neuromodulation and influences blood flow control, treatment with a magnetic field shows promise for regulating neurovascular coupling and treating vascular dysfunctions associated with aging and neurodegenerative disorders. Furthermore, magnetic treatment can enable control over the decoding of Ca signals, ultimately impacting protein synthesis. The ability to modulate calcium wave frequencies using MFsand the MF-controlled decoding of Ca signaling present promising avenues for treating diseases characterized by calcium dysregulation.
Correlative single-molecule and structured illumination microscopy of fast dynamics at the plasma membrane
Authors: Winkelmann Hauke , Richter Christian P. , Eising Jasper , Piehler Jacob , Kurre Rainer 
Published: October 2023

AbstractTotal internal reflection fluorescence (TIRF) microscopy offers powerful means to uncover the functional organization of proteins in the plasma membrane with very high spatial and temporal resolution. Traditional TIRF illumination, however, shows a Gaussian intensity profile, which is typically deteriorated by overlaying interference fringes hampering precise quantification of intensities – an important requisite for quantitative analyses in single-molecule localization microscopy (SMLM). Here, we combined flat-field illumination by using a standard πShaper with multi-angular TIR illumination by incorporating a spatial light modulator compatible with fast super-resolution structured illumination microscopy (SIM). This unique combination enabled quantitative multi-color SMLM with a highly homogenous illumination. By using a dual camera setup with optimized image splitting optics, we achieved versatile combination of SMLM and SIM with up to three channels. We deployed this setup for establishing robust detection of receptor stoichiometries based on single-molecule intensity analysis and single-molecule Förster resonance energy transfer (smFRET). Homogeneous illumination furthermore enabled long-term tracking and localization microscopy (TALM) of cell surface receptors identifying spatial heterogeneity of mobility and accessibility in the plasma membrane. By combination of TALM and SIM, spatially and molecularly heterogenous diffusion properties could be correlated with nanoscale cytoskeletal organization and dynamics.
A sexually dimorphic hepatic cycle of periportal VLDL generation and subsequent pericentral VLDLR-mediated lipoprotein re-uptake
Authors: Martini Tomaz , Gobet Cedric , Salati Andrea , Blanc Jérôme , Mookhoek Aart , Reinehr Michael , Knott Graham , Sordet-Dessimoz Jessica , Naef Felix 
Published: October 2023

ABSTRACTRecent single-cell transcriptomes revealed spatiotemporal programmes of liver function on the sublobular scale. However, how sexual dimorphism affected this space-time logic remained poorly understood. We addressed this by performing scRNA-seq in the mouse liver, which revealed that sex, space and time together markedly influence xenobiotic detoxification and lipoprotein metabolism. The very low density lipoprotein receptor (VLDLR) exhibits a pericentral expression pattern, with significantly higher mRNA and protein levels in female mice. Conversely, VLDL assembly is periportally biased, suggesting a sexually dimorphic hepatic cycle of periportal formation and pericentral uptake of VLDL. In humans,VLDLRexpression is also pericentral, with higher mRNA and protein levels in premenopausal women compared to similarly aged men. Individuals with low hepaticVLDLRexpression show a high prevalence of atherosis in the coronary artery already at an early age and an increased incidence of heart attack.
Benchmarking whole exome sequencing pipeline for predicting pathogenic variants of significance
Authors: Raju Ranjana Mariyam , Singh Ujjwal Prathap , Suravajhala Prashanth 
Published: October 2023

AbstractBenchmarking whole exome pipelines is crucial for evaluating and comparing their performance in variant calling and clinical significance annotation. It enables researchers and clinicians to assess the accuracy, sensitivity, and specificity of different pipelines and identify the most effective and reliable ones. In this study, we evaluated and compared the performance of our in-house consensus exome pipeline with a widely recognized gold standard Genome Analysis Toolkit (GATK) pipeline. Four datasets were used for evaluation, three 1000 Genome Project (1KGP) datasets and one Prostate cancer (PCa) Sample. The consensus pipeline consistently demonstrated a higher average transition-to-transversion (Ti/Tv) ratio, indicating enhanced precision in identifying single nucleotide variant (SNV) calls. This suggests that the consensus pipeline excels in effectively discerning true genetic variations from sequencing artefacts, particularly in the context of exome sequencing. Additionally, the pipeline exhibited increased sensitivity in detecting pathogenic and likely pathogenic variants in the PCa sample, further highlighting its efficacy in identifying clinically relevant variants. We also conducted a trio exome analysis with the use of two trio pipelines,viz. VarScan Trio and GATK joint calling pipelines on our erstwhile Congenital Pouch Colon (CPC) samples from our rare disease cohort which we published earlier and found that the GATK predicted a significantly higher number of variants compared to VarScan. Our study demonstrates a large potential for trio-variant calling analysis paving the way for precision medicine.
Molecular mechanisms of liposome interactions with bacterial envelopes
Authors: Scheeder Anna , Brockhoff Marius , Ward Edward N. , Kaminski Schierle Gabriele S. , Mela Ioanna , Kaminski Clemens F. 
Published: October 2023

ABSTRACTAlthough fusogenic liposomes offer a promising approach for the delivery of antibiotic payloads across the cell envelope of Gram-negative bacteria, there is still limited understanding of the individual nanocarrier interactions with the bacterial target. Using super-resolution microscopy, we characterize the interaction dynamics of positively charged fusogenic liposomes with Gram-negative (Escherichia coli) and Gram-positive (Bacillus subtilis) bacteria. The liposomes merge with the outer membrane (OM) of Gram-negative bacteria, while attachment or lipid internalization is observed in Gram-positive cells. Employing total internal reflection fluorescence microscopy, we demonstrated liposome fusion with model supported lipid bilayers. For wholeE. colicells, however, we observed heterogeneous membrane integrations, primarily involving liposome attachment and hemifusion events. With increasing lipopolysaccharide length the likelihood of full-fusion events was reduced. The integration of artificial lipids into the OM of Gram-negative cells led to membrane destabilization, resulting in decreased bacterial vitality, membrane detachment, and improved co-delivery of Vancomycin—an effective antibiotic against Gram-positive cells. These findings provide significant insights into the interactions of individual nanocarriers with bacterial envelopes at the single-cell level, uncovering effects that would be missed in bulk measurements. This highlights the importance of conducting single-particle and single-cell investigations to assess the performance of next-generation drug delivery platforms.