bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precise 3D Localization of Intracerebral Implants with a simple Brain Clearing Method
Authors: Catanese Julien , Murakami Tatsuya , Kenny Paul J. , Ibanez-Tallon Ines 
Published: December 2023

AbstractDetermining the localization of intracerebral implants in rodent brain stands as a critical final step in most physiological and behaviroral studies, especially when targeting deep brain nuclei. Conventional histological approaches, reliant on manual estimation through sectioning and slice examination, are error-prone, potentially complicating data interpretation.Leveraging recent advances in tissue-clearing techniques and light-sheet fluorescence microscopy, we introduce a method enabling virtual brain slicing in any orientation, offering precise implant localization without the limitations of traditional tissue sectioning.To illustrate the method’s utility, we present findings from the implantation of linear silicon probes into the midbrain interpeduncular nucleus (IPN) of anesthetized transgenic mice expressing chanelrhodopsin-2 and enhanced yellow fluorescent protein under the choline acetyltransferase (ChAT) promoter/enhancer regions (ChAT-Chr2-EYFP mice). Utilizing a fluorescent dye applied to the electrode surface, we visualized both the targeted area and the precise localization, enabling enhanced inter-subject comparisons. Three dimensional (3D) brain renderings, presented effortlessly in video format across various orientations, showcase the versatility of this approach.
DNA Nanostar Structures with Tunable Auxetic Properties
Authors: Du Yancheng , Li Ruixin , Madhvacharyula Anirudh S. , Swett Alexander A. , Choi Jong Hyun 
Published: December 2023

ABSTRACTAuxetic structures are unique with a negative Poisson’s ratio. Unlike regular materials, they response to external loading with simultaneous expansion or compression in all directions, rendering powerful properties advantageous in diverse applications from manufacturing to space engineering. The auxetic behaviors are determined by structural design and architecture. Such structures have been discovered in natural crystals and demonstrated synthetically with bulk materials. Recent development of DNA-based structures has pushed the unit cell size to nanometer scale. DNA nanotechnology utilizes sequence complementarity between nucleotides. By combining sequence designs with programmable self-assembly, it is possible to construct complex structures with nanoscale accuracy and to perform dynamic reconfigurations. Herein, we report a novel design of auxetic nanostars with sliding behaviors using DNA origami. Our proposed structure, inspired by an Islamic pattern, demonstrates a unit cell with two distinct reconfigurations by programming directed sliding mechanisms. Compared to previous metamaterials, the DNA nanostars show an architecture with tunable auxetic properties for the first time. We envision that this strategy may form the basis of novel metastructures with adaptability and open new possibilities in bioengineering.
Systematic analysis of cotranscriptional RNA folding using transcription elongation complex display
Authors: Kelly Skyler L. , Strobel Eric J. 
Published: December 2023

AbstractRNA can fold into structures that mediate diverse cellular functions. Understanding how RNA primary sequence directs the formation of functional structures requires methods that can comprehensively assess how changes in an RNA sequence affect its structure and function. Here we have developed a platform for performing high-throughput cotranscriptional RNA biochemical assays, calledTranscriptionElongationComplex display (TECdisplay). TECdisplay measures RNA function by fractionating a TEC library based on the activity of cotranscriptionally displayed nascent RNA. In this way, RNA function is measured as the distribution of template DNA molecules between fractions of the transcription reaction. This approach circumvents typical RNA sequencing library preparation steps that can cause technical bias. We used TECdisplay to characterize the transcription antitermination activity of 32,768 variants of theClostridium beijerinckii pflZTP riboswitch designed to perturb steps within its cotranscriptional folding pathway. Our findings establish TECdisplay as an accessible platform for high-throughput RNA biochemical assays.
Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates
Authors: Amjad Usamma , Choi Jiwon , Gibson Daniel J. , Murray Raymond , Graybiel Ann M. , Schwerdt Helen N. 
Published: December 2023

AbstractMeasuring the dynamic relationship between neuromodulators, such as dopamine, and neuronal action potentials is imperative to understand how these fundamental modes of neural signaling interact to mediate behavior. Here, we developed methods to measure concurrently dopamine and extracellular action potentials (i.e., spikes) and applied these in a monkey performing a behavioral task. Standard fast-scan cyclic voltammetric (FSCV) electrochemical (EChem) and electrophysiological (EPhys) recording systems are combined and used to collect spike and dopamine signals, respectively, from an array of carbon fiber (CF) sensors implanted in the monkey striatum. FSCV requires the application of small voltages at the implanted sensors to measure redox currents generated from target molecules, such as dopamine. These applied voltages create artifacts at neighboring EPhys-measurement sensors, producing signals that may falsely be classified as physiological spikes. Therefore, simple automated temporal interpolation algorithms were designed to remove these artifacts and enable accurate spike extraction. We validated these methods using simulated artifacts and demonstrated an average spike recovery rate of 84.5%. This spike extraction was performed on data collected from concurrent EChem and EPhys recordings made in a task-performing monkey to discriminate cell-type specific striatal units. These identified units were shown to correlate to specific behavioral task parameters related to reward size and eye-movement direction. Synchronous measures of spike and dopamine signals displayed contrasting relations to the behavioral task parameters, as taken from our small set of representative data, suggesting a complex relationship between these two modes of neural signaling. Future application of our methods will help advance our understanding of the interactions between neuromodulator signaling and neuronal activity, to elucidate more detailed mechanisms of neural circuitry and plasticity mediating behaviors in health and in disease.Significance statementWe present a simple method for recording synchronous molecular and neuronal spike signals. Conventional electrophysiological and electrochemical instruments are combined without the need for additional hardware. A custom-designed algorithm was made and validated for extracting neuronal action potential signals with high fidelity. We were able to compute cell-type specific spike activity along with molecular dopamine signals related to reward and movement behaviors from measurements made in the monkey striatum. Such combined measurements of neurochemical and extracellular action potentials may help pave the way to elucidating mechanisms of plasticity, and how neuromodulators and neurons are orchestrated to mediate behavior.
Exogenous mitochondrial transfer increases energy expenditure and attenuates adiposity gains in mice with diet-induced obesity
Authors: Namwanje Maria , Mazumdar Soumi , Stayton Amanda , Patel Prisha S. , Watkins Christine , White Catrina , Brown Chester , Eason James D. , Mozhui Khyobeni , Kuscu Cem , Pabla Navjot , Stephenson Erin J. , Bajwa Amandeep 
Published: December 2023

AbstractObesity is associated with chronic multi-system bioenergetic stress that may be improved by increasing the number of healthy mitochondria available across organ systems. However, treatments capable of increasing mitochondrial content are generally limited to endurance exercise training paradigms, which are not always sustainable long-term, let alone feasible for many patients with obesity. Recent studies have shown that local transfer of exogenous mitochondria from healthy donor tissues can improve bioenergetic outcomes and alleviate the effects of tissue injury in recipients with organ specific disease. Thus, the aim of this project was to determine the feasibility of systemic mitochondrial transfer for improving energy balance regulation in the setting of diet-induced obesity. We found that transplantation of mitochondria from lean mice into mice with diet-induced obesity attenuated adiposity gains by increasing energy expenditure and promoting the mobilization and oxidation of lipids. Additionally, mice that received exogenous mitochondria demonstrated improved glucose uptake, greater insulin responsiveness, and complete reversal of hepatic steatosis. These changes were, in part, driven by adaptations occurring in white adipose tissue. Together, these findings are proof-of-principle that mitochondrial transplantation is an effective therapeutic strategy for limiting the deleterious metabolic effects of diet-induced obesity in mice.
Effect of habitat degradation on hantavirus infection among introduced and endemic small mammals of Madagascar
Authors: Dubrulle Jérémy , Kauffman Kayla , Soarimalala Voahangy , Randriamoria Toky , Goodman Steven M. , Herrera James , Nunn Charles , Tortosa Pablo 
Published: December 2023

AbstractHantaviruses are globally distributed zoonotic pathogens capable of causing fatal disease in humans. Rodents and other small mammals are the typical reservoirs of hantaviruses, though the particular host varies regionally. Addressing the risk of hantavirus spillover from animal reservoirs to humans requires identifying the local mammal reservoirs and the predictors of infection in those animals, such as their population density and habitat characteristics. We screened native and non-native small mammals and bats in northeastern Madagascar for hantavirus infection to investigate the influence of habitat, including effects of human land use on viral prevalence. We trapped 227 bats and 1663 small mammals over 5 successive years in and around Marojejy National Park across a range of habitat types including villages, agricultural fields, regrowth areas, and secondary and semi-intact forests. Animals sampled included endemic tenrecs (Tenrecidae), rodents (Nesomyidae) and bats (6 families), along with non-native rodents (Muridae) and shrews (Soricidae). A hantavirus closely related to the previously described Anjozorobe virus infected 9.5% ofRattus rattussampled. We did not detect hantaviruses in any other species. Habitat degradation had a complex impact on hantavirus prevalence in our study system: more intensive land use increase the abundance ofR. rattus. The average body size of individuals varied between agricultural and non-agricultural land-use types, which in turn affected infection prevalence. SmallerR.rattushad lower probability of infection and were captured more commonly in villages and forests. Thus, infection prevalence was highest in agricultural areas. These findings provide new insights to the gradients of hantavirus exposure risk for humans in areas undergoing rapid land use transformations associated with agricultural practices.
Molecular Group and Correlation Guided Structural Learning for Multi-Phenotype Prediction
Authors: Zhou Xueping , Cai Manqi , Yue Molin , Celedón Juan , Ding Ying , Chen Wei , Li Yanming 
Published: December 2023

AbstractWe propose a supervised learning algorithm to perform feature selection and outcome prediction for genomic data with multi-phenotypic responses. Our algorithm particularly incorporates the genome and/or phenotype grouping structures and phenotype correlation structures in feature selection, effect estimation, and outcome prediction under a penalized multi-response linear regression model. Extensive simulations demonstrate its superior performance over its competing methods. We apply the proposed algorithm to two omics studies. In the first study, we identified novel association signals between multivariate gene expressions and high-dimensional DNA methylation profiles, providing biological insights into how CpG sites regulate gene expressions. The second study is for cell type deconvolution. Using the proposed algorithm, we were able to achieve better cell type fraction predictions using high-dimensional gene expression data.
Discovery of genomic and transcriptomic pleiotropy between kidney function and soluble receptor for advanced glycation end-products using correlated meta-analyses: The Long Life Family Study (LLFS)
Authors: Feitosa Mary F. , Lin Shiow J. , Acharya Sandeep , Thyagarajan Bharat , Wojczynski Mary K. , Kuipers Allison L. , Kulminski Alexander , Christensen Kaare , Zmuda Joseph M. , Brent Michael R. , Province Michael A. 
Published: December 2023

SummaryPatients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end-products (AGE). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole-genome sequencing and correlated meta-analyses on combined genomewide association study (GWAS)p-values in 4,182 individuals (age range: 24-110) from the Long Life Family Study (LLFS). We also conducted transcriptome-wide association studies (TWAS) on whole blood in a subset of 1,209 individuals. We identified 59 pleiotropic GWAS loci (p<5×10-8) and 17 TWAS genes (Bonferroni-p<2.73×10-6) for eGFR traits and sRAGE. TWAS genes,LSP1andMIR23AHG, were associated with eGFR and sRAGE located within GWAS loci, lncRNA-KCNQ1OT1andCACNA1A/CCDC130, respectively. GWAS variants were eQTLs in the kidney glomeruli and tubules, and GWAS genes predicted kidney carcinoma. TWAS genes harbored eQTLs in the kidney, predicted kidney carcinoma, and connected enhancer-promoter variants with kidney function-related phenotypes atp<5×10-8. Additionally, higher allele frequencies of protective variants for eGFR traits were detected in LLFS than in ALFA-Europeans and TOPMed, suggesting better kidney function in healthy-aging LLFS than in general populations. Integrating genomic annotation and transcriptional gene activity revealed the enrichment of genetic elements in kidney function and kidney diseases. The identified pleiotropic loci and gene expressions for eGFR and sRAGE suggest their underlying shared genetic effects and highlight their roles in kidney- and aging-related signaling pathways.
Signatures of transmission in within-hostM. tuberculosisvariation
Authors: Walter Katharine S. , Cohen Ted , Mathema Barun , Colijn Caroline , Sobkowiak Benjamin , Comas Iñaki , Goig Galo A. , Croda Julio , Andrews Jason R. 
Published: December 2023

AbstractBackgroundBecauseM. tuberculosisevolves slowly, transmission clusters often contain multiple individuals with identical consensus genomes, making it difficult to reconstruct transmission chains. Finding additional sources of sharedM. tuberculosisvariation could help overcome this problem. Previous studies have reportedM. tuberculosisdiversity within infected individuals; however, whether within-host variation improves transmission inferences remains unclear.MethodsTo evaluate the transmission information present in within-hostM. tuberculosisvariation, we re-analyzed publicly available sequence data from three household transmission studies, using household membership as a proxy for transmission linkage between donor-recipient pairs.FindingsWe found moderate levels of minority variation present inM. tuberculosissequence data from cultured isolates that varied significantly across studies (mean: 6, 7, and 170 minority variants above a 1% minor allele frequency threshold, outside of PE/PPE genes). Isolates from household members shared more minority variants than did isolates from unlinked individuals in the three studies (mean 98 shared minority variants vs. 10; 0.8 vs. 0.2, and 0.7 vs. 0.2, respectively). Shared within-host variation was significantly associated with household membership (OR: 1.51 [1.30,1.71], for one standard deviation increase in shared minority variants). Models that included shared within-host variation improved the accuracy of predicting household membership in all three studies as compared to models without within-host variation (AUC: 0.95versus0.92, 0.99versus0.95, and 0.93versus0.91).InterpretationWithin-hostM. tuberculosisvariation persists through culture and could enhance the resolution of transmission inferences. The substantial differences in minority variation recovered across studies highlights the need to optimize approaches to recover and incorporate within-host variation into automated phylogenetic and transmission inference.FundingNIAID: 5K01AI173385
Preliminary Analysis of the Melanoma Multimedia Educational programme for general practitioners on behalf of the Italian Melanoma Intergroup
Authors: Zamagni Federica , Falcini Fabio , Magi Serena , Bucchi Lauro , Mancini Silvia , Vattiato Rosa , Crocetti Emanuele , Falcinelli Stefano , Feliciani Claudio , Lombardo Maurizio , Melandri Davide , Re Patrizia , Ricci Francesco , Satta Rosanna Rita , Gandini Sara , Stanganelli Ignazio ,   FAD MelaMEd Working Group
Published: December 2023

ABSTRACTIntroductionAccording to the National Oncological Plan 2023-2027 on the importance of multidisciplinary and interactive e-learning training, the Italian Melanoma Intergroup (IMI) has developed MelaMEd (Melanoma Multimedia Education), a national project for general practitioners (GPs) on the prevention and detection of cutaneous melanoma through an online platform and an online course. MelaMEd enables participants to (1) recognize skin lesions that require specialist dermatological assessment, (2) select patients at high risk of melanoma and (3) be informed of the diagnosis and treatment pathway of patients with melanoma.MethodsA free online platform and online course were developed and launched in June 2022. Before starting the course, enrolled participants fill out a pre-training questionnaire concerning the basic knowledge of the disease and the recognition and management of suspicious lesions. After the course, participants will fill out the same questionnaire again. The online course will end in December 2023. Here we present a preliminary analysis of the pre-training results (January 2023-July 2023). The data have been analyzed descriptively.ResultsSo far, five healthcare centers have participated in the project for a total of 1320 participants. Of these, 298 compiled the pre-training questionnaire. Forty-seven percent of them were aged <40 years. Respondents were almost divided between GPs (47%) and resident GPs (48%). Among the theoretical questions, the “ABCDE” rule and “ugly duckling” sign are well known (96% and 91% of correct answers, respectively), but a lower percentage (68%) of respondents knows the “EFG” rule for the recognition of nodular melanomas and the statement of Breslow thickness (29%).Regarding the series of clinical images of pigmented skin lesions and their management, the percentages rate of accuracy varied from 33% to 87%: melanoma (5 cases) ranges from 36% to 71%, melanocytic nevi (3 cases) from 33% to 84%, whereas the percentages rate of referral for dermatological evaluation varied from 44% to 99%. Melanoma cases referred to dermatologist ranges from 67% to 99%.ConclusionsThis preliminary analysis on pre-training questionnaire mainly showed a lack of knowledge of the two major points of melanoma diagnosis (EFG) and management (Breslow thickness), as well as a low rate of participants. We will compare the proportions of correct answers to the questionnaires before and after the course once available.
Investigations on Clinical Validation of mutated ANKRD36 as a Novel Molecular Biomarker for Monitoring Early Progression and Timely Therapeutic Interventions in Blast Crisis CML
Authors: Alanazi Nawaf , Siyal Abdulaziz , Absar Muhammad , Shammas Masood , Mahmood Amer , Basit Sulman , AlMukhaylid Sarah , Iqbal Zafar 
Published: December 2023

AbstractBackgroundChronic Myeloid Leukemia (CML) is initiated in the bone marrow due to the chromosomal translocation t(9;22), resulting in the fusion oncogene BCR-ABL. Tyrosine kinase inhibitors (TKIs) targeting BCR-ABL have transformed fatal CML into an almost curable disease. However, TKIs lose efficacy during disease progression, and the mechanism of CML progression remains to be fully understood. Additionally, common molecular biomarkers for CML progression are lacking. Our studies previously detected ANKRD36 (c.1183_1184 delGC and c.1187_1188 dupTT) associated exclusively with advanced phase CML. However, clinical validation of this finding was pending. Therefore, this study aimed to clinically validate mutated ANKRD36 as a novel biomarker of CML progression.Materials and MethodsThe study enrolled 124 patients in all phases of CML, recruited from Mayo Hospital and Hameed Latif Hospital in Lahore, Punjab, between January 2020 and September 2023. All response criteria were adopted from the European LeukemiaNet guideline 2020. Informed consent was obtained from all study subjects. The study was approved by scientific and ethical review committees of all participating centers.Sanger sequencing was employed to detect ANKRD36 mutations in CML patients in accelerated phase (AP) (n=11) and blast crisis (BC) (n=10), with chronic-phase CML (CP-CML) patients as controls (n=103). Samples were processed using Big Dye Terminator Cycle Sequencing Ready Reaction kits and sequenced using ABI Prism 3730 Genetic Analyzer, and sequencing using forward and reverse primers for ANKRD36. Data was analyzed using SPSS version 26.ResultsDuring our study, 17% of CML patients progressed to advanced phases AP-CML n= 11 (8.9%) and BC-CML n=10 (8.1%). The chronic- and advanced-phase patients showed significant difference with respect to male-to-female ratio, hemoglobin level, WBC count, and platelet count. Sanger sequencing detected ANKRD36 mutations c.1183_1184 delGC and c.1187_1185 dupTT exclusively in all AP- and BC-CML patients but in none of the CP-CML patients. Nevertheless, mutations status was not associated with male-to-female ratio, hemoglobin level, WBC count, and platelet count, which makes ANKRD32 as an independent predictor of early and terminal disease progression in CML.ConclusionsThe study confirms ANKRD36 as a novel genomic biomarker for early and late CML progression. Further prospective studies should be carried out in this regard. ANKRD36, although fully uncharacterized in humans, shows the highest expression in bone marrow, particularly myeloid cells and correlation with high WBC count. Functional integrated genomic studies are recommended to further explore the role of ANKRD36 in the biology and pathogenesis of CML.