bluuebunny/crossref_metadata_2025_split huggingface dataset:
A ‘through-DNA’ mechanism for metal uptake-vs.-efflux regulation
Authors: Chakraborty Udit Kumar , Park Youngchan , Sengupta Kushal , Jung Won , Joshi Chandra P. , Francis Danielle H. , Chen Peng 
Published: December 2023

AbstractTransition metals like Zn are essential for all organisms including bacteria, but fluctuations of their concentrations in the cell can be lethal. Organisms have thus evolved complex mechanisms for cellular metal homeostasis. One mechanistic paradigm involves pairs of transcription regulators sensing intracellular metal concentrations to regulate metal uptake and efflux. Here we report that Zur and ZntR, a prototypical pair of regulators for Zn uptake and efflux inE. coli, respectively, can coordinate their regulation through DNA, besides sensing cellular Zn2+concentrations. Using a combination of live-cell single-molecule tracking andin vitrosingle-molecule FRET measurements, we show that unmetallated ZntR can enhance the unbinding kinetics of Zur from DNA by directly acting on Zur-DNA complexes, possibly through forming heteromeric ternary and quaternary complexes that involve both protein-DNA and protein-protein interactions. This ‘through-DNA’ mechanism may functionally facilitate the switching in Zn uptake regulation when bacteria encounter changing Zn environments; it could also be relevant for regulating the uptake-vs.-efflux of various metals across different bacterial species and yeast.
Fungi and Bacteria Occupy Distinct Spatial Niches within Carious Dentin
Authors: Sulyanto Rosalyn M. , Beall Clifford J. , Ha Kasey , Montesano Joseph , Juang Jason , Dickson John R. , Hashmi Shahr B. , Bradbury Seth , Leys Eugene J. , Edgerton Mira , Ho Sunita P. , Griffen Ann L. 
Published: December 2023

AbstractThe role of bacteria in the etiology of dental caries is long established, while the role of fungi has only recently gained more attention. The microbial invasion of dentin in advanced caries especially merits additional research. We evaluated the fungal and bacterial community composition and spatial distribution within carious dentin. Amplicon 16S rRNA gene sequencing together with quantitative PCR was used to profile bacterial and fungal species in caries-free children (n=43) and 4 stages of caries progression from children with severe early childhood caries (n=32). Additionally, healthy (n=10) and carious (n=10) primary teeth were decalcified, sectioned, and stained with Grocott’s methenamine silver, periodic acid Schiff (PAS) and calcofluor white (CW) for fungi. Immunolocalization was also performed using antibodies against fungal β-D-glucan, gram-positive bacterial lipoteichoic acid,Streptococcus mutans, andCandida albicans. We also performed field emission scanning electron microscopy (FESEM) to visualize fungi and bacteria within carious dentinal tubules. Bacterial communities observed included a high abundance ofS. mutansand theVeillonella parvulagroup, as expected. There was a higher ratio of fungi to bacteria in dentin-involved lesions compared to less severe lesions with frequent preponderance ofC. albicans,C. dubliniensis, and in one caseC. tropicalis. Grocott’s silver, PAS, CW and immunohistochemistry (IHC) demonstrated the presence of fungi within carious dentinal tubules. Multiplex IHC revealed that fungi and gram-positive bacteria primarily occupied separate dentinal tubules, with rare instances of colocalization. Similar findings were observed with multiplex immunofluorescence using anti-S. mutansand anti-C. albicansantibodies. Electron microscopy showed monomorphic bacterial and fungal biofilms within distinct dentin tubules. We demonstrate a previously unrecognized phenomenon in which fungi and bacteria occupy distinct spatial niches within carious dentin and seldom co-colonize. The potential significance of this phenomenon in caries progression warrants further exploration.
Using Unstructured Crowd-sourced Data to Evaluate Urban Tolerance of Terrestrial Native Species within a California Mega-City
Authors: Curti Joseph N. , Barton Michelle , Flores Rhay G. , Lechner Maren , Lipman Alison , Montgomery Graham A. , Park Albert Y. , Rochel Kirstin , Tingley Morgan W. 
Published: December 2023

ABSTRACTIn response to biodiversity loss and biotic community homogenization in urbanized landscapes, City managers around the world are increasingly working to conserve and increase urban biodiversity. Accordingly, around the world, previously extirpated species are (re)colonizing and otherwise infiltrating urban landscapes, while once abundant species are in various states of decline. Tracking the occurrence of traditionally urban intolerant species and loss of traditionally urban tolerant species should be a management goal of urban areas, but we generally lack tools to study this phenomenon. To address this, we first used species’ occurrences from iNaturalist, a large collaborative dataset of species observations, to measure an urban association index (UAI) for 967 native animal species that occur in the city of Los Angeles. On average, the occurrence of native species was negatively associated with our composite measure of urban intensity, with the exception of snails and slugs, which instead occur more frequently in areas of increased urban intensity. Next, we assessed 8,348 0.25 x 0.25 mile grids across the City of Los Angeles to determine the average grid-level UAI scores (i.e., a summary of the UAIs present in a grid cell, which we term Community Urban Tolerance Index or CUTI). We found that areas of higher urban intensity host more urban tolerant species, but also that taxonomic groups differ in their aggregate tolerance of urban areas, and that spatial patterns of tolerance vary between groups (e.g., mammals are not the same as birds). The framework established here was designed to be iteratively reevaluated by city managers of Los Angeles in order to track the progress of initiatives to preserve and encourage urban biodiversity, but can be rescaled to sample different regions within the city or different cities altogether to provide a valuable tool for city managers globally.
SNPs in genes related to the repair of damage to DNA in clinical isolates ofM. tuberculosis: a transversal and longitudinal approach
Authors: Pérez-Martínez DE. , Zenteno-Cuevas R 
Published: December 2023

AbstractThe presence of SNPs in genes related to DNA damage repair inM. tuberculosiscan trigger hypermutagenic phenotypes with a higher probability of generating drug resistance. The aim of this research was to compare the presence of SNPs in genes related to DNA damage repair between sensitive and DR isolates, as well as to describe the dynamics in the presence of SNPs inM. tuberculosisisolated from recently diagnosed TB patients of the state of Veracruz, Mexico. The presence of SNPs in the coding regions of 65 genes related to DNA damage repair was analyzed. Eighty-six isolates from 67 patients from central Veracruz state, Mexico, were sequenced. The results showed several SNPs in 14 genes that were only present in drug-resistant genomes. In addition, by following of 15 patients, it was possible to describe three different dynamics of appearance and evolution of non-synonymous SNPs in genes related to DNA damage repair: 1) constant fixed SNPs, 2) population substitution, and 3) gain of fixed SNPs. Further research is required to discern the biological significance of each of these pathways and their utility as markers of DR or for treatment prognosis.
Highly Multiplexed Fluorescence Microscopy with Spectrally Tunable Semiconducting Polymer Dots
Authors: Guo Ziyu , Poudel Chetan , Sarfatis Margaret C. , Yu Jiangbo , Wong Madeline , Chiu Daniel T. , Vaughan Joshua C. 
Published: December 2023

AbstractCurrent studies of biological tissues require visualizing diverse cell types and molecular interactions, creating a growing need for versatile techniques to simultaneously probe numerous targets. Traditional multiplexed imaging is limited to around five targets at once. Emerging methods utilizing sequential rounds of staining, imaging, and signal removal can probe tens of targets but require specialized hardware, time-consuming workflows, and face some challenges with sample distortion and artifacts. Here we present a new method for highly-multiplexed fluorescence microscopy using semiconducting polymer dots (Pdots) in a single round of staining and imaging. Pdots are small, bright, and photostable fluorescent probes with a wide range of tunable Stokes shifts (20–450 nm). Multiple series of Pdots with varying excitation wavelengths allow for fast (<1 minute) and single-round imaging of up to 21 targets in brain and kidney. This method is based on a simple immunofluorescence workflow, efficient use of spectral space, standard hardware, and straightforward analysis, making it widely applicable for bioimaging laboratories.
DNDesign: Enhancing Physical Understanding of Protein Inverse Folding Model via Denoising
Authors: Lee Youhan , Kim Jaehoon 
Published: December 2023

AbstractBased on the central dogma that protein structure determines its functionality, an important approach for protein sequence design is to identify promising sequences that fold into pre-designed structures based on domain knowledge. Numerous studies have introduced deep generative model-based inverse-folding, which utilizes various generative models to translate fixed backbones to corresponding sequences. In this work, we reveal that denoising training enables models to deeply capture the protein energy landscape, which previous models do not fully leverage. Based on this, we propose a novel Denoising-enhanced protein fixed backbone design (DNDesign), which combines conventional inverse-folding networks with a novel plug-in module, which learns the physical understanding via denoising training and transfers the knowledge to the entire network. Through extensive experiments, we demonstrate that DNDesign can easily be integrated into state-of-the-art models and improve performance in multiple modes, including auto-regressive, non-auto-regressive, and scaled-up scenarios. Furthermore, we introduce a fixed backbone conservation analysis based on potential energy changes, which confirms that DNDesign ensures more energetically favorable inverse-folding.
EPAS1 Attenuates Atherosclerosis Initiation at Disturbed Flow Sites through Endothelial Fatty Acid Uptake
Authors: Pirri Daniela , Tian Siyu , Tardajos-Ayllon Blanca , Irving Sophie , Donati Francesco , Allen Scott P. , Mammoto Tadanori , Vilahur Gemma , Miller Clint , Schenkel Torsten , Chambers Emily V. , Dunning Mark , Serbanovic-Canic Jovana , Botrè Francesco , Mammoto Akiko , Xu Suowen , Osto Elena , Han Weiping , Fragiadaki Maria , Evans Paul C. 
Published: December 2023

ABSTRACTBackgroundAtherosclerotic plaques form unevenly due to disturbed blood flow, causing localized endothelial cell (EC) dysfunction. Obesity exacerbates this process, but the underlying molecular mechanisms are unclear. The transcription factor EPAS1 (HIF2A) has regulatory roles in endothelium, but its involvement in atherosclerosis remains unexplored. This study investigates the potential interplay between EPAS1, obesity, and atherosclerosis.MethodsResponses to shear stress were analysed using cultured porcine aortic EC exposed to flowin vitrocoupled with metabolic and molecular analyses, and by en face immunostaining of murine aortic EC exposed to disturbed flowin vivo. Obesity and dyslipidemia were induced in mice via exposure to high-fat diet or through Leptin gene deletion. The role of Epas1 in atherosclerosis was evaluated by inducible endothelial Epas1 deletion, followed by hypercholesterolemia induction (AAV-PCSK9; high-fat diet).ResultsEn facestaining revealed EPAS1 enrichment at sites of disturbed blood flow that are prone to atherosclerosis initiation. Obese mice exhibited substantial reduction in endothelial EPAS1 expression, correlating with hyperlipidaemia. Sulforaphane, a compound with known atheroprotective effects, restored EPAS1 expression and concurrently reduced plasma triglyceride levels in obese mice. Consistently, triglyceride derivatives (free fatty acids) suppressed EPAS1 in cultured EC by upregulating the negative regulator PHD3. Clinical observations revealed that reduced plasma EPAS1 correlated with increased endothelial PHD3 in obese individuals. Functionally, endothelial EPAS1 deletion increased lesion formation in hypercholesterolemic mice, indicating an atheroprotective function. Mechanistic insights revealed that EPAS1 protects arteries by maintaining endothelial proliferation by positively regulating CD36 and LIPG expression to increase fatty acid beta-oxidation.ConclusionsEndothelial EPAS1 attenuates atherosclerosis at sites of disturbed flow by maintaining EC proliferative via fatty acid uptake and metabolism. This endothelial repair pathway is inhibited in obesity, suggesting a novel triglyceride-PHD3 modulation pathway suppressing EPAS1 expression. These findings have implications for therapeutic strategies addressing vascular dysfunction in obesity.
Exploratory study of pulsed electric field ablation on atherosclerotic plaque in a rabbit model
Authors: Xuying Ye , Jiashen Hu , Shisheng Cao , Xinyu Xu , Zhixiao Xue , Chengzhi Lu , Huijuan Yin 
Published: December 2023

AbstractNew understanding of the pathogenesis of atherosclerotic diseases has led to the emergence of new therapeutic approaches. We explored the potential therapeutic effects of pulsed field potential ablation (PFA), a non-thermal ablation technique with high tissue selectivity, on atherosclerotic plaques. Carotid arteries of 30 high-fat rabbits were dilated with a balloon to obtain atherosclerotic plaques. PFA was administered on the carotid atherosclerotic plaques with 1000V/cm, 2000V/cm, and 1000V/cm ablation followed by rapamycin infusion. There were no visible changes in blood vessels after acute ablation, but apoptosis and polarity of cells were observed in atherosclerotic plaques. At 7 and 30 days after ablation, the density of lipid deposition in the plaque was significantly reduced, and multiple layers of new arranged anterograde smooth muscle cells appeared, replacing the original atherosclerotic plaque. The residual atherosclerotic structure is sandwiched between the new smooth muscle layer and the original smooth muscle layer, which makes vascular wall thicker and makes vascular wall elasticity increased. Rapamycin delays the vascular remodeling process. Conclusion: PFA ablation can reduce lipid deposition in atherosclerotic plaques, cause vascular remodeling, and enhance vascular elasticity. We believe that it may be a potential method for the treatment of atherosclerotic plaques.
Clinical-grade whole genome sequencing-based haplarithmisis enables all forms of preimplantation genetic testing
Authors: Janssen Anouk E.J. , Koeck Rebekka M. , Essers Rick , van Dijk Wanwisa , Drüsedau Marion , Meekels Jeroen , Yaldiz Burcu , van de Vorst Maartje , Cao Ping , de Koning Bart , Hellebrekers Debby M.E.I. , Stevens Servi J.C. , Sun Su Ming , Heijligers Malou , de Munnik Sonja A. , van Uum Chris M.J. , Achten Jelle , Hamers Lars , Naghdi Marjan , Vissers Lisenka E.L.M. , van Golde Ron J.T. , de Wert Guido , Dreesen Jos C.F.M. , de Die-Smulders Christine , Coonen Edith , Brunner Han G. , van den Wijngaard Arthur , Paulussen Aimee D.C. , Esteki Masoud Zamani 
Published: December 2023

AbstractHigh-throughput sequencing technologies have increasingly led to discovery of disease-causing genetic variants, primarily in postnatal multi-cell DNA samples. However, applying these technologies to preimplantation genetic testing (PGT) in nuclear or mitochondrial DNA from single or few-cells biopsied fromin vitrofertilised (IVF) embryos is challenging. PGT aims to select IVF embryos without genetic abnormalities. Although genotyping-by-sequencing (GBS)-based haplotyping methods enabled PGT for monogenic disorders (PGT-M), structural rearrangements (PGT-SR), and aneuploidies (PGT-A), they are labour intensive, only partially cover the genome and are troublesome for difficult loci and consanguineous couples. Here, we devised a simple, scalable and universal whole genome sequencing haplarithmisis-based approach enabling all forms of PGT in a single assay. In a comparison to state-of-the-art GBS-based PGT for nuclear DNA (37 embryos, 18 families, 25 indications), shallow sequencing-based PGT (10 embryos, 3 families), and PCR-based PGT for mitochondrial DNA (10 embryos, 2 families), our approach alleviates technical limitations by decreasing whole genome amplification artifacts by 68.4%, increasing breadth of coverage by 4-fold, and reducing wet-lab turn-around-time by 2.5-fold. Importantly, this method enables trio-based PGT-A for aneuploidy origin, an approach we coin PGT-AO, detects translocation breakpoints, and nuclear and mitochondrial single nucleotide variants and indels in base-resolution.
LITERATURE REVIEW THE EFFECT OF MINDFULNESS INTERVENTIONS ON BLOOD PRESSURE AND STRESS IN HYPERTENSION PATIENTS
Authors: Mu’afiro Adin , Pandin Moses Glorino Rumambo , Nursalam  
Published: December 2023

ABSTRACTBackgroundHypertension is a significant contributor to both illness and death on a global scale. One method of managing blood pressure is through adopting a healthy lifestyle and implementing blood pressure control measures, with or without the use of medication. The objective of the review paper is to elucidate the impact of mindfulness therapies on both blood pressure and stress levels in individuals diagnosed with hypertension.MethodThe research approach employed is literature observation, wherein relevant papers published between January 2019 and December 2023 are sought by conducting searches in four databases: Scopus and Science Direct. The search criteria include publications written in English, available in open access, and with full text. The study investigates the impact of mindfulness therapies on blood pressure and stress levels in individuals with hypertension, using Proquest and CINAHL as research databasesResultsA total of 14 papers have undergone evaluation. The primary emphasis lies in mindfulness techniques aimed at lowering blood pressure and alleviating stress. A mindfulness intervention was administered in group settings, with a duration of 2 hours per week for a period of 8 weeks. Subsequently, participants engage in physical activity inside the confines of their own homes, dedicating a minimum of 45 minutes per day for a duration of 6 to 10 days per week. They also monitor their blood pressure and stress levels. Blood pressure measurements are derived from the mean of three measurements done thrice day. Following the implementation of the mindfulness intervention, there was a notable reduction in both systolic and diastolic blood pressure among the intervention group, as compared to the first measurement. The investigation revealed substantial disparities between the experimental and control groups in the mean scores of positive stress (P = 0.001) and negative stress (P = 0.001).ConclusionMindfulness can be a straightforward and cost-effective method for enhancing blood pressure and reducing stress.
A novel in vitro tubular model to recapitulate features of distal airways: The bronchioid
Authors: Maurat Elise , Raasch Katharina , Leipold Alexander M. , Henrot Pauline , Zysman Maeva , Prevel Renaud , Trian Thomas , Krammer Tobias , Bergeron Vanessa , Thumerel Matthieu , Nassoy Pierre , Berger Patrick , Saliba Antoine-Emmanuel , Andrique Laetitia , Recher Gaëlle , Dupin Isabelle 
Published: December 2023

AbstractBackgroundAirflow limitation is the hallmark of obstructive pulmonary diseases, with the distal airways representing a major site of obstruction. Although numerousin vitromodels of bronchi already exist, there is currently no culture system for obstructive diseases that reproduces the architecture and function of small airways. Here, we aimed to engineer a model of distal airways to overcome the limitations of current culture systems.MethodsWe developed a so-called bronchioid model by encapsulating human bronchial adult stem cells derived from clinical samples in a tubular scaffold made of alginate gel.ResultsThis template drives the spontaneous self-organization of epithelial cells into a tubular structure. Fine control of the level of contraction is required to establish a model of the bronchiole, which has a physiologically relevant shape and size. 3D imaging, gene expression and single-cell RNA-seq analysis of bronchioids made of bronchial epithelial cells revealed tubular organization, epithelial junction formation and differentiation into ciliated and goblet cells. Ciliary beating is observed, at a decreased frequency in bronchioids made of cells from COPD patients. The bronchioid can be infected by rhinovirus. An air-liquid interface is introduced that modulates gene expression.ConclusionHere, we provide a proof of concept of a perfusable bronchioid with proper mucociliary and contractile functions. The key advantages of our approach, such as the air-liquid interface, lumen accessibility, recapitulation of pathological features and possible assessment of clinically relevant endpoints, will make our pulmonary organoid-like model a powerful tool for preclinical studies.
Rapid modeling of an ultra-rare epilepsy variant in wild-type mice by in utero prime editing
Authors: Robertson Colin D. , Davis Patrick , Richardson Ryan R. , Iffland Philip H. , Vieira Daiana C. O. , Steyert Marilyn , McKeon Paige N. , Romanowski Andrea J. , Crutcher Garrett , Jašarević Eldin , Wolff Steffen B. E. , Mathur Brian N. , Crino Peter B. , Bale Tracy L. , Dick Ivy E. , Poulopoulos Alexandros 
Published: December 2023

AbstractGenerating animal models for individual patients within clinically-useful timeframes holds great potential toward enabling personalized medicine approaches for genetic epilepsies. The ability to rapidly incorporate patient-specific genomic variants into model animals recapitulating elements of the patient’s clinical manifestations would enable applications ranging from validation and characterization of pathogenic variants to personalized models for tailoring pharmacotherapy to individual patients. Here, we demonstrate generation of an animal model of an individual epilepsy patient with an ultra-rare variant of the NMDA receptor subunit GRIN2A, without the need for germline transmission and breeding. Using in utero prime editing in the brain of wild-type mice, our approach yielded high in vivo editing precision and induced frequent, spontaneous seizures which mirrored specific elements of the patient’s clinical presentation. Leveraging the speed and versatility of this approach, we introduce PegAssist, a generalizable workflow to generate bedside-to-bench animal models of individual patients within weeks. The capability to produce individualized animal models rapidly and cost-effectively will reduce barriers to access for precision medicine, and will accelerate drug development by offering versatile in vivo platforms to identify compounds with efficacy against rare neurological conditions.
Blue light irradiation induces pollen tube rupture in various flowering plants
Authors: Sugi Naoya , Susaki Daichi , Mizuta Yoko , Kinoshita Tetsu , Maruyama Daisuke 
Published: December 2023

AbstractPollen tubes exhibit one of the fastest apical growth rates among plant cells. Maintaining the proper balance between turgor pressure and cell wall synthesis at the pollen tube tip is crucial for this rapid growth, and any disruption can result in pollen tube rupture. In our study, we reveal that exposure to short-wavelength visible light, specifically blue light, induces pollen tube rupture. The frequency of pollen tube rupture increases in an intensity-dependent manner. Additionally, we observed Ca2+influx after blue light irradiation, accompanying with either pollen tube rupture or a temporary halt in elongation. These findings offer insights into the interplay between pollen tube integrity maintenance and Ca2+influx at the pollen tube tip, presenting a novel and efficient method to control pollen tube burst.Subject Areas(1) growth and development(11) new methodology