bluuebunny/crossref_metadata_2025_split huggingface dataset:
A genetic screen for temperature-sensitive morphogenesis-defective Caenorhabditis elegans mutants
Authors: Jud Molly C , Lowry Josh , Padilla Thalia , Clifford Erin , Yang Yuqi , Fennell Francesca , Miller Alexander K , Hamill Danielle , Harvey Austin M , Avila-Zavala Martha , Shao Hong , Nguyen Tran Nhan , Bao Zhirong , Bowerman Bruce 
Published: March 2021

Abstract
Morphogenesis involves coordinated cell migrations and cell shape changes that generate tissues and organs, and organize the body plan. Cell adhesion and the cytoskeleton are important for executing morphogenesis, but their regulation remains poorly understood. As genes required for embryonic morphogenesis may have earlier roles in development, temperature-sensitive embryonic-lethal mutations are useful tools for investigating this process. From a collection of ∼200 such Caenorhabditis elegans mutants, we have identified 17 that have highly penetrant embryonic morphogenesis defects after upshifts from the permissive to the restrictive temperature, just prior to the cell shape changes that mediate elongation of the ovoid embryo into a vermiform larva. Using whole genome sequencing, we identified the causal mutations in seven affected genes. These include three genes that have roles in producing the extracellular matrix, which is known to affect the morphogenesis of epithelial tissues in multicellular organisms: the rib-1 and rib-2 genes encode glycosyltransferases, and the emb-9 gene encodes a collagen subunit. We also used live imaging to characterize epidermal cell shape dynamics in one mutant, or1219ts, and observed cell elongation defects during dorsal intercalation and ventral enclosure that may be responsible for the body elongation defects. These results indicate that our screen has identified factors that influence morphogenesis and provides a platform for advancing our understanding of this fundamental biological process.
AC. elegansgenome-wide RNAi screen for altered levamisole sensitivity identifies genes required for muscle function
Authors: Chaya Timothy , Patel Shrey , Smith Erin M , Lam Andy , Miller Elaine N , Clupper Michael , Kervin Kirsten , Tanis Jessica E 
Published: March 2021

AbstractAt the neuromuscular junction (NMJ), postsynaptic ionotropic acetylcholine receptors (AChRs) transduce a chemical signal released from a cholinergic motor neuron into an electrical signal to induce muscle contraction. To identify regulators of postsynaptic function, we conducted a genome-wide RNAi screen for genes required for proper response to levamisole, a pharmacological agonist of ionotropic L-AChRs at the Caenorhabditis elegans NMJ. A total of 117 gene knockdowns were found to cause levamisole hypersensitivity, while 18 resulted in levamisole resistance. Our screen identified conserved genes important for muscle function including some that are mutated in congenital myasthenic syndrome, congenital muscular dystrophy, congenital myopathy, myotonic dystrophy, and mitochondrial myopathy. Of the genes found in the screen, we further investigated those predicted to play a role in endocytosis of cell surface receptors. Loss of the Epsin homolog epn-1 caused levamisole hypersensitivity and had opposing effects on the levels of postsynaptic L-AChRs and GABAA receptors, resulting in increased and decreased abundance, respectively. We also examined other genes that resulted in a levamisole-hypersensitive phenotype when knocked down including gas-1, which functions in Complex I of the mitochondrial electron transport chain. Consistent with altered ATP synthesis impacting levamisole response, treatment of wild-type animals with levamisole resulted in L-AChR–dependent depletion of ATP levels. These results suggest that the paralytic effects of levamisole ultimately lead to metabolic exhaustion.
Methods and tools for spatial mapping of single-cell RNAseq clusters inDrosophila
Authors: Mohr Stephanie E , Tattikota Sudhir Gopal , Xu Jun , Zirin Jonathan , Hu Yanhui , Perrimon Norbert 
Published: March 2021

AbstractSingle-cell RNA sequencing (scRNAseq) experiments provide a powerful means to identify clusters of cells that share common gene expression signatures. A major challenge in scRNAseq studies is to map the clusters to specific anatomical regions along the body and within tissues. Existing data, such as information obtained from large-scale in situ RNA hybridization studies, cell type specific transcriptomics, gene expression reporters, antibody stainings, and fluorescent tagged proteins, can help to map clusters to anatomy. However, in many cases, additional validation is needed to precisely map the spatial location of cells in clusters. Several approaches are available for spatial resolution in Drosophila, including mining of existing datasets, and use of existing or new tools for direct or indirect detection of RNA, or direct detection of proteins. Here, we review available resources and emerging technologies that will facilitate spatial mapping of scRNAseq clusters at high resolution in Drosophila. Importantly, we discuss the need, available approaches, and reagents for multiplexing gene expression detection in situ, as in most cases scRNAseq clusters are defined by the unique coexpression of sets of genes.
A novel allele of SIR2 reveals a heritable intermediate state of gene silencing
Authors: Farris Delaney , Saxton Daniel S , Rine Jasper 
Published: March 2021

Abstract
Genetic information acquires additional meaning through epigenetic regulation, the process by which genetically identical cells can exhibit heritable differences in gene expression and phenotype. Inheritance of epigenetic information is a critical step in maintaining cellular identity and organismal health. In Saccharomyces cerevisiae, one form of epigenetic regulation is the transcriptional silencing of two mating-type loci, HML and HMR, by the SIR-protein complex. To focus on the epigenetic dimension of this gene regulation, we conducted a forward mutagenesis screen to identify mutants exhibiting an epigenetic or metastable silencing defect. We utilized fluorescent reporters at HML and HMR, and screened yeast colonies for epigenetic silencing defects. We uncovered numerous independent sir1 alleles, a gene known to be required for stable epigenetic inheritance. More interestingly, we recovered a missense mutation within SIR2, which encodes a highly conserved histone deacetylase. In contrast to sir1Δ, which exhibits states that are either fully silenced or fully expressed, this sir2 allele exhibited heritable states that were either fully silenced or expressed at an intermediate level. The heritable nature of this unique silencing defect was influenced by, but not completely dependent on, changes in rDNA copy number. Therefore, this study revealed a heritable state of intermediate silencing and linked this state to a central silencing factor, Sir2.
The case for using mapped exonic non-duplicate reads when reporting RNA-sequencing depth: examples from pediatric cancer datasets
Authors: Beale Holly C , Roger Jacquelyn M , Cattle Matthew A , McKay Liam T , Thompson Drew K A , Learned Katrina , Lyle A Geoffrey , Kephart Ellen T , Currie Rob , Lam Du Linh , Sanders Lauren , Pfeil Jacob , Vivian John , Bjork Isabel , Salama Sofie R , Haussler David , Vaske Olena M 
Published: March 2021

Abstract

Background
The reproducibility of gene expression measured by RNA sequencing (RNA-Seq) is dependent on the sequencing depth. While unmapped or non-exonic reads do not contribute to gene expression quantification, duplicate reads contribute to the quantification but are not informative for reproducibility. We show that mapped, exonic, non-duplicate (MEND) reads are a useful measure of reproducibility of RNA-Seq datasets used for gene expression analysis.

Findings
In bulk RNA-Seq datasets from 2,179 tumors in 48 cohorts, the fraction of reads that contribute to the reproducibility of gene expression analysis varies greatly. Unmapped reads constitute 1–77% of all reads (median [IQR], 3% [3–6%]); duplicate reads constitute 3–100% of mapped reads (median [IQR], 27% [13–43%]); and non-exonic reads constitute 4–97% of mapped, non-duplicate reads (median [IQR], 25% [16–37%]). MEND reads constitute 0–79% of total reads (median [IQR], 50% [30–61%]).

Conclusions
Because not all reads in an RNA-Seq dataset are informative for reproducibility of gene expression measurements and the fraction of reads that are informative varies, we propose reporting a dataset's sequencing depth in MEND reads, which definitively inform the reproducibility of gene expression, rather than total, mapped, or exonic reads. We provide a Docker image containing (i) the existing required tools (RSeQC, sambamba, and samblaster) and (ii) a custom script to calculate MEND reads from RNA-Seq data files. We recommend that all RNA-Seq gene expression experiments, sensitivity studies, and depth recommendations use MEND units for sequencing depth.
Perception-Action Integration Is Modulated by the Catecholaminergic System Depending on Learning Experience
Authors: Eggert Elena , Bluschke Annet , Takacs Adam , Kleimaker Maximilian , Münchau Alexander , Roessner Veit , Mückschel Moritz , Beste Christian 
Published: March 2021

Abstract

Background
The process underlying the integration of perception and action is a focal topic in neuroscientific research and cognitive frameworks such as the theory of event coding have been developed to explain the mechanisms of perception-action integration. The neurobiological underpinnings are poorly understood. While it has been suggested that the catecholaminergic system may play a role, there are opposing predictions regarding the effects of catecholamines on perception-action integration.

Methods
Methylphenidate (MPH) is a compound commonly used to modulate the catecholaminergic system. In a double-blind, randomized crossover study design, we examined the effect of MPH (0.25 mg/kg) on perception-action integration using an established “event file coding” paradigm in a group of n = 45 healthy young adults.

Results
The data reveal that, compared with the placebo, MPH attenuates binding effects based on the established associations between stimuli and responses, provided participants are already familiar with the task. However, without prior task experience, MPH did not modulate performance compared with the placebo.

Conclusions
Catecholamines and learning experience interactively modulate perception-action integration, especially when perception-action associations have to be reconfigured. The data suggest there is a gain control–based mechanism underlying the interactive effects of learning/task experience and catecholaminergic activity during perception-action integration.
Out With the Old and in With the New? Factors Involved in Migration of Older and Newer Generation Stereotactic Breast Biopsy Markers
Authors: Stahl Brian , Li Yufeng , Hermecz Brittany , Woodard Stefanie 
Published: March 2021

Abstract

Objective
The purpose of this study was to investigate four commonly used stereotactic biopsy markers, two older and two newer generation, assessing percentage migration and factors influencing migration distance.

Methods
This was an IRB–approved retrospective review of upright stereotactic breast biopsies from May 2018 to May 2020 involving either older (Cork, Hourglass) or newer (Vision, X-shaped) generation markers. Markers were assessed for migration rate by two-sample Z-test and migration distance by analysis of variance. Univariate analysis was used to assess relationships between marker type and generation, patient characteristics, breast composition and thickness, procedure techniques, trainee involvement, and complications, correlating with migration distance. Multivariable analysis was performed for variables with P-value &lt; 0.1 on univariate analysis. Tukey’s test was used to compare groups (P &lt; 0.05).

Results
In total, 732 stereotactic biopsies were performed with 508 using a Cork, Hourglass, Vision, or X-shaped marker. Overall migration rate was 181/508 (35.6%) with no difference between markers. Breast thickness and density were negatively associated with migration distance in univariate analysis. Older marker migration distance was greater than newer (2.6 cm vs 1.9 cm, respectively), which was significant after adjusting for breast thickness and density (P = 0.037). Density was a significant factor in migration distance, comparing fatty to nonfatty breasts (P &lt; 0.05) in univariate analysis.

Conclusion
No difference in migration rate was seen between the four markers. Vision and X-shaped markers demonstrate lower migration distance than Cork and Hourglass in multivariate analysis. There is an inverse relationship between breast density and marker migration distance.
Using Payroll Tax Variation to Unpack the Black Box of Firm-Level Production
Authors: Benzarti Youssef , Harju Jarkko 
Published: March 2021

AbstractThis paper uses quasi-experimental variation in payroll tax rates in Finland to investigate how firms use their input factors. We find that higher payroll tax rates lead to large employment responses and have no effects on employee-level earnings. As payroll taxes increase, firms substitute away from low-skilled, routine, and manual workers. Higher firm-level payroll tax rates also slightly decrease the total output of firms. Our results imply that firm-level production and input factor choices are clearly affected by payroll taxes.
Design of a New Distributed NoSQL Database with Distributed Hash Tables
Authors: San Román Guzmán Agustín , Valdeolmillos Diego , Rivas Alberto , González Arrieta Angélica , Chamoso Pablo 
Published: March 2021

Abstract
Databases play a fundamental role in today’s world, being used by most companies, especially those that offer services through the Internet. Today there is a wide variety of database models, each adapted for use according to the specific requirements of each application. Traditionally, the relational models with centralized architectures have been used mostly due to their simplicity and general-purpose query language, which made relational systems suitable for almost any application. However, with the growth of the Internet in recent decades, both in the number of users and in the amount of information, those centralized models began to suffer availability and scalability issues. To address those issues, the use of decentralized architectures and alternative database models began to arise, eventually replacing relational databases and centralized architectures when the requirements on availability and scalability are high. Those database models alternative to the traditional relational model are grouped under the name of NoSQL (Not only Structured Query Language). In this article, we present a NoSQL database developed as an end of degree work, with a flexible data model based on documents and a fully decentralized architecture based on the Gossip protocol for node discovery and a distributed hash table, in particular the rendezvous hashing algorithm, used to distribute and replicate the data across all the nodes. The main goals of the system are to achieve high availability (the data should be almost always accessible) and high scalability (the system should be able to scale by increasing the number of nodes to increase its capacity both on data and number of users). High availability is achieved thanks to the replication of the data, while high scalability is achieved by its decentralized architecture, which allows multiple entry points from the requests, and the data distribution, effectively increasing the database capacity by increasing the number of nodes.
Climatic factors and population demography in big-eared woodrat,Neotoma macrotis
Authors: Rolland Virginie , Tietje William D , Polyakov Anne Y , Chaudhary Vratika , Oli Madan K 
Published: March 2021

AbstractChanges in temperature and rainfall patterns can have marked impacts on small mammal populations that inhabit environments with highly fluctuating water availability. With projected increases in droughts and fewer but more intense rainfall events in the Southwestern United States, the persistence of many wildlife populations may be threatened. Our goal was to assess how temperature and rainfall during distinct dry and wet seasons influenced the dynamics of a population of big-eared woodrats (Neotoma macrotis) in a mixed oak woodland of coastal central California. We applied Pradel’s temporal symmetry models to our 21-year biannual capture–mark–recapture data set (1993–2014) to determine the effects of climatic factors on the woodrats’ apparent survival (Φ) and recruitment rate (f). Monthly Φ averaged 0.945 ± 0.001 and varied with season. Monthly f was 0.064 ± 0.001 in the wet season (f was fixed to 0 in the dry season). Monthly population growth rate (λ) varied from 0.996 ± 0.001 during the dry season to 1.001 ± 0.001 during the wet season, which indicated a stable population (0.999 ± 0.001). Total rainfall from the previous season and mean temperature during the same season positively influenced Φ and f. By contrast, Φ and f were negatively influenced by mean temperature from the previous season and total rainfall in the same season. The resulting λ fluctuated with total rainfall, particularly in the wet season. Our results suggest that the big-eared woodrat population may not be substantially affected by warm temperatures per se, potentially because of the microclimate provided by its stick houses. We also discuss its adaptability to local food resources and relatively slow life history relative to other cricetids, and propose that the big-eared woodrat population may be equipped to cope with future climate change.
Progression of Frailty in Survivors of Childhood Cancer: A St. Jude Lifetime Cohort Report
Authors: Delaney Angela , Howell Carrie R , Krull Kevin R , Brinkman Tara M , Armstrong Gregory T , Chemaitilly Wassim , Wilson Carmen L , Mulrooney Daniel A , Wang Zhaoming , Lanctot Jennifer Q , Johnson Ruth E , Krull Matthew R , Partin Robyn E , Shelton Kyla C , Srivastava Deo Kumar , Robison Leslie L , Hudson Melissa M , Ness Kirsten K 
Published: March 2021

Abstract

Background
Some adult survivors of childhood cancers develop frailty at higher rates than expected based on their chronological age. This study examined the incidence of frailty among survivors at 10 or more years after diagnosis, frailty prevalence 5 years later, and risk factors for becoming frail.

Methods
Frailty was measured at study entry and 5 years later. Logistic regression tested the associations of several factors with having frailty at 5 years for all participants and separately by sex and by study entry frailty status. Cox models evaluated the hazard of death associated with entry frailty considering covariates.

Results
Cancer survivors (range = 0-22 years at diagnosis, median = 7 years) were ages 18-45 years (median = 30 years) at study entry. Frailty prevalence increased from 6.2% (95% confidence interval [CI] = 5.0% to 7.5%) to 13.6% (95% CI = 11.9% to 15.4%) at 5 years. Risk factors for frailty at follow-up among all survivors included chest radiation 20 Gy or higher (odds ratio [OR] = 1.98, 95% CI = 1.29 to 3.05), cardiac (OR = 1.58, 95% CI = 1.02 to 2.46), and neurological (OR = 2.58, 95% CI = 1.69 to 3.92) conditions; lack of strength training (OR = 1.74, 95% CI = 1.14 to 2.66); sedentary lifestyle (OR = 1.75, 95% CI = 1.18 to 2.59); and frailty at study entry (OR = 11.12, 95% CI = 6.64 to 18.61). The strongest risk factor for death during follow-up was prior frailty (OR = 3.52, 95% CI = 1.95 to 6.32).

Conclusions
Prevalent frailty more than doubled at 5 years after study entry among adult childhood cancer survivors. Frailty at entry was the strongest risk factor for death. Because treatment exposures cannot be changed, mitigation of other risk factors for frailty, including lack of strength training and sedentary lifestyle, may decrease risk of adverse health events and improve longevity in survivors.
Novel Glutamine Antagonist JHU395 Suppresses MYC-Driven Medulloblastoma Growth and Induces Apoptosis
Authors: Pham Khoa , Maxwell Micah J , Sweeney Heather , Alt Jesse , Rais Rana , Eberhart Charles G , Slusher Barbara S , Raabe Eric H 
Published: March 2021

Abstract
Medulloblastoma is the most common malignant pediatric brain tumor. Amplification of c-MYC is a hallmark of a subset of poor-prognosis medulloblastoma. MYC upregulates glutamine metabolism across many types of cancer. We modified the naturally occurring glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) by adding 2 promoeities to increase its lipophilicity and brain penetration creating the prodrug isopropyl 6-diazo-5-oxo-2-(((phenyl (pivaloyloxy) methoxy) - carbonyl) amino) hexanoate, termed JHU395. This prodrug was shown to have a 10-fold improved CSF-to-plasma ratio and brain-to-plasma ratio relative to DON. We hypothesized that JHU395 would have superior cell penetration compared with DON and would effectively and more potently kill MYC-expressing medulloblastoma. JHU395 treatment caused decreased growth and increased apoptosis in multiple human high-MYC medulloblastoma cell lines at lower concentrations than DON. Parenteral administration of JHU395 in Nu/Nu mice led to the accumulation of micromolar concentrations of DON in brain. Treatment of mice bearing orthotopic xenografts of human MYC-amplified medulloblastoma with JHU395 increased median survival from 26 to 45 days compared with vehicle control mice (p &lt; 0.001 by log-rank test). These data provide preclinical justification for the ongoing development and testing of brain-targeted DON prodrugs for use in medulloblastoma.
Predicting photosynthetic capacity in tobacco using shortwave infrared spectral reflectance
Authors: Sexton Thomas , Sankaran Sindhuja , Cousins Asaph B 
Published: March 2021

Abstract
Plateauing yield and stressful environmental conditions necessitate selecting crops for superior physiological traits with untapped potential to enhance crop performance. Plant productivity is often limited by carbon fixation rates that could be improved by increasing maximum photosynthetic carboxylation capacity (Vcmax). However, Vcmax measurements using gas exchange and biochemical assays are slow and laborious, prohibiting selection in breeding programs. Rapid hyperspectral reflectance measurements show potential for predicting Vcmax using regression models. While several hyperspectral models have been developed, contributions from different spectral regions to predictions of Vcmax have not been clearly identified or linked to biochemical variation contributing to Vcmax. In this study, hyperspectral reflectance data from 350–2500 nm were used to build partial least squares regression models predicting in vivo and in vitro Vcmax. Wild-type and transgenic tobacco plants with antisense reductions in Rubisco content were used to alter Vcmax independent from chlorophyll, carbon, and nitrogen content. Different spectral regions were used to independently build partial least squares regression models and identify key regions linked to Vcmax and other leaf traits. The greatest Vcmax prediction accuracy used a portion of the shortwave infrared region from 2070 nm to 2470 nm, where the inclusion of fewer spectral regions resulted in more accurate models.