bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human biodistribution and radiation dosimetry of the demyelination tracer [18F]3F4AP
Authors: Brugarolas Pedro , Wilks Moses Q. , Noel Jacqueline , Kaiser Julia-Ann , Vesper Danielle R. , Ramos-Torres Karla M. , Guehl Nicolas J. , Macdonald-Soccorso Marina T. , Rice Peter A. , Yokell Daniel L. , Lim Ruth , Normandin Marc D. , Fakhri Georges El 
Published: May 2022

AbstractPurpose[18F]3F4AP is a novel PET radiotracer that targets voltage-gated potassium (K+) channels and has shown promise for imaging demyelinated lesions in animal models of neurological diseases. This study aimed to evaluate the biodistribution, safety and radiation dosimetry of [18F]3F4AP in healthy human volunteers.MethodsFour healthy volunteers (2 female) underwent a 4-hour dynamic PET scan from cranial vertex to mid-thigh using multiple bed positions after administration of 368 ± 17.9 MBq (9.94 ± 0.48 mCi) of [18F]3F4AP was produced in a cGMP laboratory under IND authorization from the FDA. Volumes of interest for relevant organs were manually drawn guided by the CT and PET images and time-activity curves (TACs) were extracted. Radiation dosimetry was estimated from the integrated TACs using OLINDA software. Safety assessments included measuring vital signs immediately before and after the scan, monitoring for adverse events, as well as obtaining a comprehensive metabolic panel (CMP) and electrocardiogram (ECG) within 30 days before and after the scan. The study was approved by the institutional review board (IRB) and registered at clinicaltrials.gov (NCT04710550) before commencement.Results[18F]3F4AP distributed throughout the body with the highest levels of activity in the kidneys, urinary bladder, stomach, liver, spleen and brain and with low accumulation in muscle and fat. The tracer cleared quickly from circulation and from most organs. The clearance of the tracer was noticeably faster than previously reported clearance in nonhuman primates (NHPs). The average effective dose (ED) across all subjects was 12.1 ± 2.2 µSv/MBq, which is lower than the estimated ED from the NHP studies (21.6 ± 0.6 µSv/MBq) as well as the ED of other fluorine-18 radiotracers such as [18F]FDG (∼20 µSv/MBq). No differences in ED between males and females were observed. No substantial changes in safety assessments or adverse events were recorded.ConclusionThe biodistribution and radiation dosimetry of [18F]3F4AP in humans is reported for the first time. The average total ED across four subjects was lower than most 18F-labeled PET tracers. The tracer and study procedures were well tolerated and no adverse events occurred.
Using a reverse genetics system to generate recombinant SARS-CoV-2 expressing robust levels of reporter genes
Authors: Ye Chengjin , Martinez-Sobrido Luis 
Published: May 2022

ABSTRACTReporter-expressing recombinant virus represents an excellent option and a powerful tool to investigate, among others, viral infection, pathogenicity, and transmission, as well as to identify therapeutic compounds that inhibit viral infection and prophylactic vaccines. To combat the still ongoing coronavirus disease 2019 (COVID-19) pandemic, we have established a robust bacterial artificial chromosome (BAC)-based reverse genetics (RG) system to rapidly generate recombinant severe acute respiratory syndrome coronavirus 2 (rSARS-CoV-2) to study the contribution of viral proteins in viral pathogenesis. In addition, we have also engineered reporter-expressing recombinant viruses in which we place the reporter genes upstream of the viral nucleocapsid (N) gene to promote high levels of reporter gene expression that facilitates the study of SARS-CoV-2 in vitro and in vivo. Although successful, the genetic manipulation of the BAC containing the entire SARS-CoV-2 genome of ∼30,000 nucleotides, is challenging. Herein, we depict the technical details to engineer rSARS-CoV-2 expressing reporter genes using the BAC-based RG approach. We describe i) assembly of the full-length (FL) SARS-CoV-2 genome sequences into the empty pBeloBAC, ii) verification of the pBeloBAC-FL, iii) cloning of a Venus reporter gene into the pBeloBAC-FL, and iv) recovery of the Venus-expressing rSARS-CoV-2. By following this protocol, researchers with basic molecular biology and gene engineering techniques knowledge will be able to generate wild-type and reporter-expressing rSARS-CoV-2.
Alzheimer’s disease rewires gene coexpression networks coupling different brain regions
Authors: Mitra Sanga , B P Kailash , C R Srivatsan , Saikumar Naga Venkata , Philip Philge , Narayanan Manikandan 
Published: May 2022

AbstractConnectome studies have revealed how neurodegenerative diseases like Alzheimer’s disease (AD) disrupt functional and structural connectivity among brain regions, but the molecular basis of such disruptions is less studied, with most genomic studies focusing on within-brain-region molecular analyses. We performed an inter-brain-region differential correlation (DC) analysis of postmortem human brain RNA-seq data available for four brain regions – frontal pole, superior temporal gyrus, parahippocampal gyrus, and inferior frontal gyrus – from Mount Sinai Brain Bank for hundreds of AD vs. control samples. For any two brain regions, our DC analysis identifies all pairs of genes across these regions whose coexpression/correlation strength in the AD group differs significantly from that in the Control group, after adjusting for cell type compositional effects to better capture cell-intrinsic changes. Such DC gene pairs provided information complementary to known differentially expressed genes in AD, and highlighted extensive rewiring of the network of cross-region coexpression-based couplings among genes. The most vulnerable region in AD, parahippocampal gyrus, showed the most rewiring in its coupling with other brain regions. Decomposing the DC network into bipartite (region-region) gene modules revealed enrichment for synaptic signaling and ion transport pathways in several modules, revealing the dominance of five genes (BSN, CACNA1B, GRIN1, IQSEC2, and SYNGAP1). AD cerebrospinal fluid biomarkers (AD-CSF), neurotransmitters, secretory proteins, ligand and receptors were found to be part of the DC network, suggesting how pathways comprising such signaling molecules could mediate region-region communication. A module enriched for AD GWAS (Genome-wide Association Studies) signals is also enriched for NF-κβ signaling pathway, a key mediator of brain inflammation in AD. Beyond modules, we also identified individual genes that act as hubs of AD dysregulation across regions, such as ZKSCAN1 (Zinc Finger with KRAB And SCAN Domains) – this gene is known to be linked to AD in GWAS studies but via unknown mechanisms, and the specific DC interactions of ZKSCAN1 found in this study can be used to dissect these mechanisms. Thus, our inter-region DC framework provides a valuable new perspective to comprehend AD aetiology.
Brain Serotonergic Fibers Suggest Anomalous Diffusion-Based Dropout in Artificial Neural Networks
Authors: Lee Christian , Zhang Zheng , Janušonis Skirmantas 
Published: May 2022

ABSTRACTRandom dropout has become a standard regularization technique in artificial neural networks (ANNs), but it is currently unknown whether an analogous mechanism exists in biological neural networks (BioNNs). If it does, its structure is likely to be optimized by hundreds of millions of years of evolution, which may suggest novel dropout strategies in large-scale ANNs. We propose that the brain serotonergic fibers meet some of the expected criteria because of their ubiquitous presence, stochastic structure, and ability to grow throughout the individual’s lifespan. Since the trajectories of serotonergic fibers can be modeled as paths of anomalous diffusion processes, in this proof-of-concept study we investigated a dropout algorithm based on the superdiffusive fractional Brownian motion (FBM). This research contributes to biologically-inspired regularization in ANNs.
Benchmarking de novo assembly methods on metagenomic sequencing data
Authors: Zhang Zhenmiao , Yang Chao , Fang Xiaodong , Zhang Lu 
Published: May 2022

ABSTRACTMetagenome assembly is an efficient approach to deciphering the “microbial dark matter” in the microbiota based on metagenomic sequencing, due to the technical challenges involved in isolating and culturing all microbes in vitro. Although short-read sequencing has been widely used for metagenome assembly, linked- and long-read sequencing have shown their advancements by providing long-range DNA connectedness in assembly. Many metagenome assembly tools use dedicated algorithms to simplify the assembly graphs and resolve the repetitive sequences in microbial genomes. However, there remains no comprehensive evaluation of the pros and cons of various metagenomic sequencing technologies in metagenome assembly, and there is a lack of practical guidance on selecting the appropriate metagenome assembly tools. Therefore, this paper presents a comprehensive benchmark of 15 de novo assembly tools applied to 32 metagenomic sequencing datasets obtained from simulation, mock communities, or human stool samples. These datasets were generated using mainstream sequencing platforms, such as Illumina and BGISEQ short-read sequencing, 10x Genomics linked-read sequencing, and PacBio and Oxford Nanopore long-read sequencing. The assembly tools were extensively evaluated against many criteria, which revealed that compared with the other sequencing technologies, long-read assemblers generated the highest contig continuity but failed to reveal some medium- and high-quality metagenome-assembled genomes (MAGs). In addition, hybrid assemblers using both short- and long-read sequencing were promising tools to both improve contig continuity and increase the number of near-complete MAGs. This paper also discussed the running time and peak memory consumption of these tools and provided practical guidance on selecting them.
Regression Based Accuracy Estimation for Multiple Sequence Alignment
Authors: Cedillo Luis , Ruiz Hector Richart , DeBlasio Dan 
Published: May 2022

AbstractMultiple sequence alignment plays an important role in many important analyses. However, aligning multiple biological sequences is a complex task, thus many tools have been developed to align sequences under a biologically-inspired objective function. But these tools require a user-defined parameter vector, which if chosen incorrectly, can greatly impact down-stream analysis. Parameter Advising addresses this challenge of selecting input-specific parameter vectors by comparing alignments produced by a carefully constructed set of parameter configurations. In an ideal scenario, we would rank alignments based on their accuracy. However, in practice, we do not have a reference from which to calculate accuracy. Therefore, it becomes necessary toestimatethe accuracy to rank the alignments. One solution involves the use of estimators such asFacet. The accuracy estimatorFacetcomputes an estimate of accuracy as a linear combination of efficiently-computable feature functions. In this work we introduce two new estimators calledLead(short forLearnedaccuracyestimator from largedatasets) which use the same underlying feature functions asFacetbut are built on top of highly efficient machine learning protocols, allowing us to take advantage of a larger training corpus.Note about previous versionsA previous version of this paper was released on bioRxiv and presented the results of our previous study (Facet) with an error. This error has been corrected, and the conclusions made have been updated based on this new data. This corrected version stands as reference for anyone who may have encountered the versions with inaccuracies.
Resilient anatomy and local microplasticity of naïve and stress hematopoiesis
Authors: Wu Qingqing , Zhang Jizhou , Johnson Courtney B. , Slaughter Anastasiya , Weinhaus Benjamin , McKnight Morgan , Sherman Bryan E. , Shao Tzu-Yu , Song Baobao , Filippi Marie Dominique , Grimes H. Leighton , Way Sing Sing , Kofron J. Matthew , Lucas Daniel 
Published: May 2022

ABSTRACTThe bone marrow has an extraordinary capacity to adjust blood cell production to meet physiological demands in response to insults. The spatial organization of normal and stress responses is largely unknown due to the lack of methods to visualize most steps of blood production. Here we develop strategies to image multipotent hematopoiesis, megakaryopoiesis, erythropoiesis, and lymphopoiesis in mice. We combine these with imaging of myelopoiesis1 to define the anatomy of hematopoiesis in homeostasis, after acute insults, and during geriatric age. Blood production takes place via long-range migration of multipotent progenitors away from stem cells. Lineage-committed progenitors are then serially recruited to blood vessels where they contribute to lineage-specific microanatomical structures, composed of progenitors and immature cells, which function as production lines for mature blood cells. This anatomy is durable and resilient to insults as it was maintained after hemorrhage, acute bacterial infection, and with aging. Production lines enable hematopoietic plasticity as they differentially -and selectively-modulate their numbers and output in response to acute insults and then return to homeostasis. In geriatric mice the number of production lines is maintained, but their microanatomy becomes permanently remodeled in a cell- and lineage-specific manner indicating chronic anatomical adaptations to hematopoietic aging. Our studies uncover the sophisticated and durable anatomy of blood production -defined by distinct migratory behaviors depending on the maturation stage- and identify discrete microanatomical production lines that confer plasticity to hematopoiesis.
PEG-Free Polyion Complex Nanocarriers for Brain Derived Neurotrophic Factor
Authors: Fay James M. , Lim Chaemin , Finkelstein Anna , Batrakova Elena , Kabanov Alexander V. 
Published: May 2022

AbstractMany therapeutic formulations incorporate poly(ethylene glycol) (PEG) as a stealth component to minimize early clearance. However, PEG is immunogenic and susceptible to accelerated clearance after multiple administrations. Here, we present two novel reformulations of a polyion complex (PIC), originally comprised of poly(ethylene glycol)113-b-poly(glutamic acid)50 (PEG-PLE) and brain derived neurotrophic factor (BDNF), termed Nano-BDNF (Nano-BDNF PEG-PLE). We replace the PEG based block copolymer with two new polymers, poly(sarcosine)127-b-poly(glutamic acid)50 (PSR-PLE) and poly(methyl-2-oxazolines)38-b-poly(oxazolepropanoic acid)27-b-(poly(methyl-2-oxazoline)38 (PMeOx-PPaOx-PMeOx) which are driven to association with BDNF via electrostatic interactions and hydrogen bonding to form a PIC. Formulation using a microfluidic mixer yields small and narrowly disperse nanoparticles which associate following similar principles. Additionally, we demonstrate that encapsulation does not inhibit access by the receptor kinase, which effects BDNF’s physiologic benefits. Finally, we investigate the formation of nascent nanoparticles through a series of characterization experiments and isothermal titration experiments which show the effects of pH in the context of particle self-assembly. Our findings indicate that thoughtful reformulation of PEG based, therapeutic PICs with non-PEG alternatives can be accomplished without compromising the self-assembly of the PIC.
Tristetraproline in breast cancer: treat or trick?
Authors: Serhii Kropyvko , Anastasiia Hubiernatorova , Oksana Mankovska , Liubov Syvak , Nataliia Verovkina , Sergii Lyalkin , Kyrylo Lavrynenko , Iryna Ivasechko , Rostyslav Stoika , Alla Rynditch 
Published: May 2022

AbstractBreast cancer is one of the most common types of cancer. It is very heterogeneous, hence still complicated to diagnose despite of decades of research. Post-transcriptional regulation of gene expression is crucial for modulation of cell networking and is performed via different regulatory molecules. Tristetraproline (TTP) is RNA-binding protein which binds to AU-rich elements within its target mRNAs and negatively regulates multiple transcripts, including pro-inflammatory and pro-oncogenic. Its expression level correlates with patient outcomes in different types of cancer and is considered as a potential molecular marker. Here we examined TTPs expression level in different molecular subtypes of breast cancer. Our findings show that TTP expression is significantly higher in HER2-enriched breast cancer compared to other types and adjacent tissues. We also investigated changes in the TTPs methylation status under temozolomide and doxorubicin treatment in MCF-7 cell line and found that temozolomide decreased TTPs methylation, which can potentially improve patient prognosis. In contrast, another well-known anticancer agent, doxorubicin, promoted TTPs methylation, which may impair an expected therapeutic effect of this drug.
Rates and spectra of de novo structural mutation in Chlamydomonas reinhardtii
Authors: López-Cortegano Eugenio , Craig Rory J. , Chebib Jobran , Balogun Eniolaye J. , Keightley Peter D. 
Published: May 2022

AbstractGenetic variation originates from several types of spontaneous mutation, including single nucleotide substitutions, short insertions and deletions (INDELs), and larger structural changes. Structural mutations (SMs) drive genome evolution and are thought to play major roles in evolutionary adaptation, speciation and genetic disease, including cancers. Sequencing of mutation accumulation (MA) lines has provided estimates of rates and spectra of single nucleotide and INDEL mutations in many species, yet the rate of new SMs is largely unknown. Here, we use long-read sequencing to determine the full mutation spectrum in MA lines derived from two strains (CC-1952 and CC-2931) of the green alga Chlamydomonas reinhardtii. The SM rate is highly variable between strains and MA lines, and SMs represent a substantial proportion of all mutations in both strains (CC-1952 6%; CC-2931 12%). The SM spectra also differs considerably between the two strains, with almost all inversions and translocations occurring in CC-2931 MA lines. This variation is associated with heterogeneity in the number and type of active transposable elements (TEs), which comprise major proportions of SMs in both strains (CC-1952 22% and CC-2931 38% of SMs). In CC-2931, a Crypton and a previously undescribed type of DNA element caused 71% of chromosomal rearrangements, while in CC-1952 a Dualen LINE was associated with 87% of duplications. Other SMs, notably many large duplications in CC-2931, were likely products of various double-strand break repair pathways. Our results demonstrate that diverse types of SMs occur at substantial rates and support prominent roles for SMs and TEs in evolution.
DocumentingBombus nevadensisin Minnesota, with some notes on discerning it fromB. auricomus(Hymenoptera: Apidae)
Authors: Portman Zachary M. , Dolan Chan 
Published: May 2022

AbstractIn the face of well-documented declines in multiple bumblebee species, it is important to accurately identify species and properly delineate species ranges. Here, we document the range ofBombus auricomus(Robertson) andB. nevadensisCresson in Minnesota, with particular reference to the unexpected discovery ofB. nevadensisin St. Paul. We clarify the relative ranges of these two species and provide additional information on how to reliably identify them in Minnesota using color patterns and morphology, including differences in male genitalia. Our results support the consensus thatB. auricomusandB. nevadensisare distinct species. Community science records were integral to fully documenting the range ofB. nevadensisin Minnesota. Our findings demonstrate the value of community science data, though it highlights the need for experts to check the data and to be mindful of biases in observations around population centers.
In vivo selection reveals long non-coding RNAs implicated in colon to liver metastasis
Authors: Soroosh Artin , Padua David M. , Videlock Elizabeth , Bui Diane , Patel Ami , Pothoulakis Charalabos , Rankin Carl Robert 
Published: May 2022

AbstractColorectal cancer (CRC) is the third most common malignancy in both American men and women. Most of the deaths attributed to CRC are a result of metastatic spread to the liver. In this study, colon cancer cells that highly metastasized to liver in vivo were compared to less metastatic parental cells to investigate the role for long non-coding RNAs (lncRNAs) in CRC metastasis. The highly metastatic daughter cells (LS-3B) were found to be 63-fold more metastatic than the parental cell line (LS-PAR) in vivo. A lncRNA microarray comparing LS-PAR and LS-3B cells revealed that 104 lncRNAs had fold changes > 2.0 and an FDR < 0.05. Real time PCR mediated validation revealed many lncRNAs exhibited high fold changes such as a 60-fold increase in LOC101448202, a 20-fold increase in MRPL23-AS1 and 50-fold decreases in GNAS-AS1 and LOC101928131. In vivo metastasis differences could be recapitulated in vitro as LS-3B cells closed wounds faster than their parental LS-PAR cells. However, intestinal epithelial cancer cells with robust downregulation of MRPL23-AS1, C1QTNF1-AS1, GNAS-AS1, LINCR-0002 and LOC101448202 failed to display differences in comparison to controls in in vitro migration assays. Three of the five lncRNAs with microarray probes for currently available GEO-datasets were significantly altered in liver CRC-associated tumor biopsies as compared to the primary tumor of non-metastatic CRC. Further studies on the lncRNAs identified will better define their roles in metastasis and how they might be useful if targeted therapeutically.
Finding meaning in our everyday moments: testing a novel intervention to increase employee well-being
Authors: Nichols Austin Lee , Klussman Kristine , Langer Julia 
Published: May 2022

PurposeThe benefits of meaning in the workplace are abundant. However, few opportunities exist to increase meaning among employees in ways that result in desired organizational impacts. The current study developed two new mindfulness-based interventions designed to ultimately increase both job and life satisfaction.Design/methodology/approachOver five days, 67 participants either: (1) Reported their daily activities, (2) Additionally rated the meaningfulness of each hour, or (3) Additionally planned to increase the meaning of the least meaningful activities. At the beginning and end of the week, they also reported their job satisfaction and life satisfaction.FindingsResults suggested that listing daily activities and rating the meaningfulness of each hour was most beneficial. Compared to only listing daily activities, this group experienced greater job and life satisfaction. In contrast, the group that additionally attempted to increase the meaningfulness of their daily activities did not perform better on either of these measures.Practical implicationsSpending only a few minutes focusing on recognizing the meaning in one's daily activities can improve one's job and life satisfaction. As such, organizations may consider encouraging engagement in such a task either at the end of the workday or at home. Doing so may result in an increase in both how satisfied they are at home and at work.Originality/valueThis provides initial evidence for a short intervention that may greatly increase the well-being of employees at work and home.