bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor necrosis factor is a necroptosis-associated alarmin
Authors: Pinci Francesca , Gaidt Moritz M. , Jung Christophe , Nagl Dennis , Kuut Gunnar , Hornung Veit 
Published: August 2022

AbstractNecroptosis is a form of regulated cell death that can occur downstream of several immune pathways. While previous studies have shown that dysregulated necroptosis leads to strong inflammatory responses, little is known about the identity of the endogenous molecules that trigger necroptosis-mediated inflammatory responses. Using a reductionist in vitro model, we found that soluble TNF is strongly released in the context of necroptosis. On the one hand, necroptosis promotes TNF translation by inhibiting negative regulatory mechanisms acting at the post-transcriptional level. On the other hand, necroptosis markedly enhances TNF release by activating ADAM proteases. In studying TNF release at single-cell resolution, we found that TNF release triggered by necroptosis is activated in a switch-like manner and exceeds steady-state TNF processing in magnitude and speed. Although this shedding response precedes massive membrane damage, it is closely associated with lytic cell death. In fact, we found that lytic cell death induction using a pore-forming toxin also triggers TNF shedding, indicating that the activation of ADAM proteases is not strictly related to the necroptotic pathway but associated with biophysical changes of the cell membrane upon lytic cell death. These results demonstrate that lytic cell death, particularly necroptosis, is a critical trigger for TNF release and thus qualify TNF as a necroptosis-associated alarmin.
Spatial neglect after stroke is reduced when lying inside a 3T MRI scanner
Authors: Karnath Hans-Otto , Rosenzopf Hannah , Stammler Britta , Smaczny Stefan , Lindner Axel 
Published: August 2022

AbstractRecently, it was discovered that the static magnetic field of an MRI scanner not only causes horizontal vestibular nystagmus in healthy individuals but, in addition, leads to a horizontal bias of spatial orienting and exploration that closely resembles the one observed in stroke patients with spatial neglect (a disorder of spatial attention and exploration). The present study asked whether the behavioral effects of this magnetic vestibular stimulation (MVS) can be inverted and thus be used to reduce the pathological bias of stroke patients with spatial neglect. Indeed, when patients with left-sided spatial neglect entered the scanner with their feet first, i.e., with the magnetic field vector pointing from head to toes, MVS inside the scanner reduced the ipsilesionally biased distribution of overt attention and the corresponding neglect of the left parts of the search-space. Thus, an intervention as simple as lying in a 3T MRI scanner bears the potential to become an integral part of a future strategy for treating spatial neglect.
CTRR-ncRNA: A Translation-oriented Knowledgebase for Cancer Resistance and Recurrence Associated Non-coding RNAs
Authors: Tang Tong , Liu Xingyun , Wu Rongrong , Shen Li , Ren Shumin , Shen Bairong 
Published: August 2022

AbstractCancer therapy resistance and recurrence (CTRR) are the dominant causes of death in cancer patients. Recent studies have indicated that non-coding RNAs (ncRNAs) can not only reverse the resistance to cancer therapy but also are crucial biomarkers for the evaluation and prediction of CTRR. Herein, we developed CTRR-ncRNA, a knowledgebase of CTRR-associated ncRNAs, aiming to provide an accurate and comprehensive resource for research involving association between CTRR and ncRNAs. Compared to most of the existing cancer databases, CTRR-ncRNA is focused on the clinical characterization of cancers, including cancer subtypes, as well as survival outcomes and response to personalized therapy of cancer patients. Information pertaining to biomarker ncRNAs has also been documented for the development of personalized CTRR prediction. A user-friendly interface and several functional modules have been incorporated into the database. Based on the preliminary analysis of genotype–phenotype relationships, universal ncRNAs have been found to be potential biomarkers for CTRR. The CTRR-ncRNA is a translation-oriented knowledgebase and it provides a valuable resource for mechanistic investigations and explainable artificial intelligence-based modelling. CTRR-ncRNA is freely available to the public at http://ctrr.bioinf.org.cn/.
Reduced fibrous capsule elastic fibers from biologic ECM-enveloped CIEDs in minipigs, supported with a novel compression mechanics model
Authors: de Guzman Roche C. , Meer Allison S. , Mathews Aidan A. , Israel Atara R. , Moses Michael T. , Sams Clarence M. , Deegan Daniel B. 
Published: August 2022

AbstractBACKGROUNDFibrous capsules (Fb) in response to cardiovascular implantable electronic devices (CIEDs), including a pacemaker (P) system, can produce patient discomfort and difficulties in revision surgery due partially to their increased compressive strength, previously linked to elevated tissue fibers.OBJECTIVETo quantify structural proteins, determine if biologic extracellular matrix-enveloped CIEDs (PECM) caused differential Fb properties, and to implement a realistic mechanical model.METHODSRetrieved Fb (-P and -PECM) from minipigs were subjected to biomechanical (shear oscillation and uniaxial compression) and histological (collagen I and elastin) analyses.RESULTSFb-PECM showed significant decreases compared to Fb-P in: low strain-loss modulus (390 vs. 541 Pa) across angular frequencies, high strain-compressive elastic modulus (1043 vs. 2042 kPa), and elastic fiber content (1.92 vs. 3.15 μg/mg tissue). Decreases in elastin were particularly noted closer to the implant’s surface (Fb-PECM = 71% vs. Fb-P = 143% relative to dermal elastin at mid-tangential sections) and verified with a solid mechanics hyperelasticity with direction-dependent fiber viscoelasticity compression simulation (r2 ≥ 98.9%).CONCLUSIONSThe biologic envelope composed of decellularized porcine small intestine submucosa ECM for CIEDs promoted fibrous tissues with less elastic fibers. Novel compression modeling analyses directly correlated this singular reduction to more desirable subcutaneous tissue mechanics.
Integration of external biomass reactions into existing metabolic models
Authors: García María Moscardó , Pacheco Maria , Sauter Thomas 
Published: August 2022

SummaryCurrently, seven biomass objective functions have been defined in human metabolic reconstructions. The integration of published biomass reactions into alternative models can contribute to the prediction power of the model. Thus, in this work, we present a workflow to integrate reactions and biomass functions originating from several genome-scale reconstructions into models other than their home models. Additionally, a benchmark to identify the biomass that confers the highest prediction accuracy in terms of gene essentiality and growth predictions is provided.For complete details on the use and execution of this protocol, please refer to Moscardó García et al. (2021).
Whole genome assembly and annotation of the lucerne weevilSitona discoideus
Authors: Katuwal Mandira , Bhattarai Upendra R. , Phillips Craig B. , Gemmell Neil J. , Dowle Eddy 
Published: August 2022

AbstractWeevils are a diverse insect group that includes many economically important invasive pest species. Despite their importance and diversity, only nine weevil genomes have been sequenced, representing a tiny fraction of this heterogeneous taxon. The genusSitonaconsists of over 100 species, includingSitona discoideus(Coleoptera: Curculionidae: Entiminae), commonly known as lucerne (or alfalfa root) weevil.Sitona discoideusis an important pest of forage crops, particularlyMedicagospecies. Using a dual sequencing approach with Oxford Nanopore MinION long-reads and 10x Genomics linked-read sequencing, we generated a high-quality hybrid genome assembly ofS. discoideus. Benchmarks derived from evolutionarily informed expectations of gene content for near-universal single-copy orthologs comparison (BUSCO) scores are above 96% for single-copy orthologs derived from eukaryotes, arthropods, and insects. With ade novorepeat library, Repeatmasker annotated 81.45% of the genome as various repeat elements, of which 22.1% were unclassified. Using the MAKER2 pipeline, we annotated 10,008 protein-coding genes and 13,611 mRNAs. Furthermore, 68.84% of total predicted mRNAs and 67.90% of predicted proteins were functionally annotated to one or more of InterPro, gene ontology, and Pfam databases. This high-quality genome assembly and annotation will enable the development of critical novel genetic pest control technologies and act as an essential reference genome for broader population genetics and weevil comparative genetic studies.
Characterization of the Y Chromosome in Newfoundland and Labrador: Evidence of a Founder Effect
Authors: Zurel Heather , Bhérer Claude , Batten Ryan , MacMillan Margaret E. , Demiriz Sedat , Mirhendi Sadra , Gilbert Edmund , Cavalleri Gianpiero L. , Leach Richard A. , Scott Roderick E. M. , Mugford Gerald , Randhawa Ranjit , Symington Alison L. , Stephens J. Claiborne , Phillips Michael S. 
Published: August 2022

AbstractThe population of Newfoundland and Labrador (NL) is largely derived from settlers who migrated primarily from England and Ireland in the 1700-1800s. Previously described as an isolated founder population, based on historical and demographic studies, data on the genetic ancestry of this population remains fragmentary. Here we describe the largest investigation of patrilineal ancestry in NL. To determine the paternal genetic structure of the population, 1,110 Y chromosomes from an NL based cohort were analyzed using 5,761 Y-specific markers. We identified 160 distinct paternal haplotypes, the majority of which (71.4%) belong to the R1b haplogroup. When NL is compared with global reference populations, the haplotype composition and frequencies of the NL paternal lineages primarily resemble the English and Irish ancestral source populations. There is also evidence for genetic contributions from Basque, French, Portuguese, and Spanish fishermen and early settlers that frequented NL. The population structure shows geographical and religious clustering that can be associated with the settlement of ancestral source populations from England and Ireland. For example, the R1b-M222 haplotype, seen in people of Irish descent, is found clustered in the Irish-settled Southeast region of NL. The clustering and expansion of Y haplotypes in conjunction with the geographical and religious clusters illustrate that limited subsequent in-migration, geographic isolation and societal factors have contributed to the genetic substructure of the NL population and its designation as a founder population.
A Topological Study of a Surface Signaling Network and Possible Implications for Neural Dynamics
Authors: Sen Siddhartha , Ryan Tomás J. , Muldowney David , Stamenov Plamen S. , Pezzoli Maurizio 
Published: August 2022

SUMMARYTheoretical neuroscience is progressing strongly with novel representations of the brain, enhanced by the constant increase of computational power now available. New models suggest new ways to understand how complex brain events are emerging and explore the mechanisms of storing memory. However, there are major conceptual theoretical problems that remain unaddressed. Current theoretical methods are very capable reacting to experimental results and modeling both neural signaling and structure. Yet they still fall short to throw light on how the brain creates its own information code, or relate the variety of brain signals observed, or explain where and how memories are stored. We present here with topology as our main tool, a mathematical structure that demonstrates that circuit architecture and signal can correlate, while preserving information. This concept would imply a possible substrate for memory recording, that despite so far not been observed in biological organisms, has been already demonstrated on solid state physics and is consistent with conventional understandings of neurobiology.
Plantar flexor deficits following Achilles tendon rupture: a novel small animal dynamometer and detailed instructions
Authors: Tang My M. , Nuss Courtney A. , Fogarty Natalie , Baxter Josh R. 
Published: August 2022

AbstractPlantar flexor functional deficits measured using joint dynamometry are associated with poor outcomes in patients following Achilles tendon rupture. In this study, we developed a small animal dynamometer to quantify functional deficits in a rat Achilles tendon rupture model. Like our reported plantar flexor deficits in patients recovering from Achilles tendon ruptures, we found in our small animal model functional deficits across the ankle range of motion, resulting in an average 34% less positive work being done compared to the uninjured contralateral limb. These functional deficits are similar to 38% less plantar flexor work done by patients who were treated non-surgically in our prior research. Further, these deficits were greater in plantar flexion than dorsiflexion, which agree with clinical complaints of limited function during tasks like jumping and hiking. These findings highlight the impact of muscle-tendon loading during early tendon healing on long-term plantar flexor function and serve as compelling evidence that our Sprague Dawley rat model of an Achilles tendon rupture recapitulates the human disease. We provide thorough documentation for other groups to build their own dynamometers, which can be modified to meet unique experimental criteria.SIGNIFIGANCEPreclinical models are critical tools for translating knowledge discovery to clinical decision making. We developed a low-cost and flexible joint dynamometer that quantifies joint function in small animals. Here, we used a rat model to test the implications of Achilles tendon ruptures not surgically repaired on plantar flexor function. We found that Achilles tendon ruptures in a rodent model closely resemble the functional deficits our group has observed in patients.
Temporal Regulation of Cold Transcriptional Response in Switchgrass
Authors: Ranaweera Thilanka , Brown Brianna N.I. , Wang Peipei , Shiu Shin-Han 
Published: August 2022

ABSTRACTSwitchgrass low-land ecotypes have significantly higher biomass but lower cold tolerance compared to up-land ecotypes. Understanding the molecular mechanisms underlying cold response, including the ones at transcriptional level, can contribute to improving tolerance of high-yield switchgrass under chilling and freezing environmental conditions. Here, by analyzing an existing switchgrass transcriptome dataset, the temporalcis-regulatory basis of switchgrass transcriptional response to cold is dissected computationally. We found that the number of cold-responsive genes and enriched Gene Ontology terms increased as duration of cold treatment increased from 30 min to 24 hours, suggesting an amplified response/cascading effect in cold-responsive gene expression. To identify genomic sequences likely important for regulating cold response, machine learning models predictive of cold response were established usingk-mer sequences enriched in the genic and flanking regions of cold-responsive genes but not non-responsive genes. Thesek-mers, referred to as putativecis-regulatory elements (pCREs) are likely regulatory sequences of cold response in switchgrass. There are in total 655 pCREs where 54 are important in all cold treatment time points. Consistent with this, eight of 35 known cold-responsive CREs were similar to top-ranked pCREs in the models and only these eight were important for predicting temporal cold response. More importantly, most of the top-ranked pCREs were novel sequences in cold regulation. Our findings suggest additional sequence elements important for cold-responsive regulation previously not known that warrant further studies.
Uncertain Precision: Neurobiological and Physiological Correlates of Conservative Confidence Bias
Authors: Allen Micah , Hauser Tobias U. , Schwarzkopf Dietrich Samuel , Dolan Raymond J. , Rees Geraint 
Published: August 2022

AbstractCorrectly estimating the influence of uncertainty on our decisions is a critical metacognitive faculty. However, the relationship between sensory uncertainty (or its inverse, precision), decision accuracy, and subjective confidence is currently unclear. Although some findings indicate that healthy adults exhibit an illusion of over-confidence, under-confidence in response to sensory uncertainty has also been reported. One reason for this ambiguity is that stimulus intensity and precision are typically confounded with one another, limiting the ability to assess their independent contribution to metacognitive biases. Here we report four psychophysical experiments controlling these factors, finding that healthy human participants are systematically under-confident when discriminating low-precision stimuli. This bias remains even when decision accuracy and reaction time are accounted for, indicating that a performance-independent computation partially underpins the influence of sensory precision on confidence. We further show that this influence is linked to fluctuations in arousal and individual differences in the neuroanatomy of the left superior parietal lobe and middle insula. These results illuminate the neural and physiological correlates of precision misperception in metacognition.Significance StatementThe ability to recognize the influence of sensory uncertainty on our decisions underpins the veracity of self-monitoring, or metacognition. In the extreme, a systematic confidence bias can undermine decision accuracy and potentially underpin disordered self-insight in neuropsychiatric illness. Previously it was unclear if metacognition accurately reflects changes in sensory precision, in part due to confounding effects of stimulus intensity and precision. Here we overcome these limitations to repeatedly demonstrate a robust precision-related confidence bias. Further, we reveal novel neuroanatomical and physiological markers underlying this metacognitive bias. These results suggest a unique state-based computational mechanism may drive subjective confidence biases and further provide new avenues for investigating maladaptive awareness of uncertainty in neuropsychiatric disorders.
Genome-wide Profiling of Histone Modifications inPlasmodium falciparumusing CUT&RUN
Authors: Morillo Riward Campelo , Harris Chantal T. , Kennedy Kit , Kafsack Björn F.C. 
Published: August 2022

AbstractWe recently adapted a CUT&RUN protocol for genome-wide profiling of chromatin modifications in the human malaria parasitePlasmodium. Using the step-by-step protocol described below, we were able to generate high quality profiles of multiple histone modifications using only a small fraction of the cells required for ChIPseq. Using antibodies against two commonly profiled histone modifications, H3K4me3 and H3K9me3, we show here that CUT&RUN profiling is highly reproducible and closely recapitulates previously published ChIPseq-based abundance profiles of histone marks. Finally, we show that CUT&RUN requires substantially lower sequencing coverage for accurate profiling compared to ChIPseq.
Formulation excipients and their role in insulin stability and association state in formulation
Authors: Maikawa Caitlin L. , Nguyen Leslee T. , Mann Joseph L. , Appel Eric A. 
Published: August 2022

ABSTRACTWhile excipients are often overlooked as the “inactive” ingredients in pharmaceutical formulations, they often play a critical role in protein stability and absorption kinetics. Recent work has identified an ultrafast absorbing insulin formulation that is the result of excipient modifications. Specifically, the insulin monomer can be isolated by replacing zinc and the phenolic preservative metacresol with phenoxyethanol as an antimicrobial agent and an amphiphilic acrylamide copolymer excipient for stability. A greater understanding is needed of the interplay between excipients, insulin association state, and stability in order to optimize this formulation. Here, we formulated insulin with different preservatives and stabilizing excipient concentrations using both insulin lispro and regular human insulin and assessed the insulin association states using analytical ultracentrifugation as well as formulation stability. We determined that phenoxyethanol is required to eliminate hexamers and promote a high monomer content even in a zinc-free lispro formulation. There is also a concentration dependent relationship between the concentration of polyacrylamide-based copolymer excipient and insulin stability, where a concentration greater than 0.1 g/mL copolymer is required for a mostly monomeric zinc-free lispro formulation to achieve stability exceeding that of Humalog in a stressed aging assay. Further, we determined that under the formulation conditions tested zinc-free regular human insulin remains primarily hexameric and is not at this time a promising candidate for rapid-acting formulations.
Effects of fire regime on the bird community in an Amazonian savanna
Authors: Coelho Laís Araújo , Ritter Camila Duarte , Lima Albertina Pimentel , Cintra Renato , Magnusson William E. , Sanaiotti Tânia Margarete 
Published: August 2022

ABSTRACTSavanna ecosystems are maintained by fires with a fire-adapted biota, and savannas occur in Amazonia in patches surrounded by tropical forest. Different fire regimes can generate structurally diverse vegetation, and the composition of savanna bird assemblages is known to be closely related to vegetation structure. However, long-term approaches and interaction of fire with other environmental factors need to be explored for the better understanding of the effects of fire on birds. In an Amazonian landscape composed by savanna and forest, we investigated the effects of different fire regimes in a 12-ha area in three periods through 23 years. We also examined the effects of frequency and extent of fires, tree cover, and distance to forest on bird composition in twelve 3.7- ha savanna plots. Birds were surveyed with mist-nets and species were classified as to their habitat use by comparison of registers in forest and savanna plots through visual/acoustical surveys. After 13 years without fire, many forest species colonized the area and some savanna species were lost. Fire regime affected avifauna assemblages. The avifauna was sensitive to the occurrence of fires. After one fire event in a plot that had not burned for 12 years, some savanna species returned. These results highlight the effects of the fire regime on birds and indicate that many savanna bird species depend on the occurrence of regular fires.