bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kif9 is an active kinesin motor required for ciliary beating and proximodistal patterning of motile axonemes
Authors: Konjikusic Mia J. , Lee Chanjae , Yue Yang , Shrestha Bikram D. , Nguimtsop Ange M. , Horani Amjad , Brody Steven , Prakash Vivek N. , Gray Ryan S. , Verhey Kristen J. , Wallingford John B. 
Published: August 2021

AbstractMost motile cilia have a stereotyped structure of nine microtubule outer doublets and a single central pair of microtubules. The central pair microtubules are surrounded by a set of proteins, termed the central pair apparatus. A specific kinesin, Klp1 projects from the central pair and contributes to ciliary motility in Chlamydomonas. The vertebrate orthologue, Kif9 is required for beating in mouse sperm flagella, but the mechanism of Kif9/Klp1 function remains poorly defined. Here, using Xenopus epidermal multiciliated cells, we show that Kif9 is necessary for ciliary motility as well as leads to defects in the distal localization of not only central pair proteins, but also radial spokes and dynein arms. In addition, single-molecule assays in vitro revealed that Xenopus Kif9 is a processive motor, though like axonemal dyneins it displays no processivity in ciliary axonemes in vivo. Thus, our data suggest that Kif9 plays both indirect and direct role in ciliary motility.
NORDIC Increases the Sensitivity and Preserves the Spatiotemporal Precision of fMRI Responses
Authors: Dowdle Logan T. , Vizioli Luca , Moeller Steen , Akçakaya Mehmet , Olman Cheryl , Ghose Geoffrey , Yacoub Essa , Uğurbil Kâmil 
Published: August 2021

AbstractAs the neuroimaging field moves towards detecting smaller effects at higher spatial resolutions, and faster sampling rates, there is increased attention given to the deleterious contribution of unstructured, thermal noise. Here, we critically evaluate the performance of a recently developed reconstruction method, termed NORDIC, for suppressing thermal noise using datasets acquired with various field strengths, voxel sizes, sampling rates, and task designs.Following minimal preprocessing, statistical activation (t-values) of NORDIC processed data was compared to the results obtained with alternative denoising methods. Additionally, we examined the consistency of the estimates of task responses at the single-voxel, single run level, using a finite impulse response (FIR) model. To examine the potential impact on effective image resolution, the overall smoothness of the data processed with different methods was estimated. Finally, to determine if NORDIC alters or removes important temporal information, we employed an exhaustive leave-p-out cross validation approach, using FIR task responses to predict held out timeseries, quantified using R2.After NORDIC, the t-values are increased, an improvement comparable to what could be achieved by 1.5 voxels smoothing, and task events are clearly visible and have less cross-run error. These advantages are achieved in the absence of large changes in estimates of spatial smoothness. Cross-validated R2s based on the FIR models show that NORDIC is not measurably distorting the temporal structure of the data and is the best predictor of non-denoised time courses. The results demonstrate that analyzing 1 run of data after NORDIC produces results equivalent to using 2 to 3 original runs and that NORDIC performs equally well across a diverse array of functional imaging protocols.Significance StatementFor functional neuroimaging, the increasing availability of higher field strengths and ever higher spatiotemporal resolutions has led to concomitant increase in concerns about the deleterious effects of thermal noise. Historically this noise source was suppressed using methods that reduce spatial precision such as image blurring or averaging over a large number of trials or sessions, which necessitates large data collection efforts. Here, we critically evaluate the performance of a recently developed reconstruction method, termed NORDIC. Across datasets varying in field strength, voxel sizes, sampling rates, and task designs, NORDIC produces substantial gains in data quality. Both conventional t-statistics derived from general linear models and coefficients of determination for predicting unseen data are improved, while avoiding meaningful increases in typical estimates of image smoothness or substantial losses of temporal information.
Redesigning the Eterna100 for the Vienna 2 folding engine
Authors: Koodli Rohan V. , Rudolfs Boris , Wayment-Steele Hannah K. ,   Eterna Structure Designers, Das Rhiju 
Published: August 2021

AbstractThe rational design of RNA is becoming important for rapidly developing technologies in medicine and biochemistry. Recent work has led to the development of several RNA secondary structure design algorithms and corresponding benchmarks to evaluate their performance. However, the performance of these algorithms is linked to the nature of the underlying algorithms for predicting secondary structure from sequences. Here, we show that an online community of RNA design experts is capable of modifying an existing RNA secondary structure design benchmark (Eterna100) with minimal alterations to address changes in the folding engine used (Vienna 1.8 updated to Vienna 2.4). We tested this new Eterna100-V2 benchmark with five RNA design algorithms, and found that neural network-based methods exhibited reduced performance in the folding engine they were evaluated on in their respective papers. We investigated this discrepancy, and determined that structural features, previously classified as difficult, may be dependent on parameters inherent to the RNA energy function itself. These findings suggest that for optimal performance, future algorithms should focus on finding strategies capable of solving RNA secondary structure design benchmarks independently of the free energy benchmark used. Eterna100-V1 and Eterna100-V2 benchmarks and example solutions are freely available at https://github.com/eternagame/eterna100-benchmarking.
Wear and Tear of the Intestinal Visceral Musculature by Intrinsic and Extrinsic Factors
Authors: Kim Ho D. , So Eric , Lee Jiae , Wang Yi , Gill Vikram S. , Gorbacheva Anna , Han Hee Jin , Ng Katelyn G.-L. , Ning Ken , Pranoto Inez K.A. , Cabrera Alejandra J.H. , Eom Dae Seok , Kwon Young V. 
Published: August 2021

AbstractThe gut visceral musculature plays essential roles in not only moving substances through the lumen but also maintaining the function and physiology of the gut. Although the development of the visceral musculature has been studied in multiple model organisms, how it degenerates is poorly understood. Here, we employ the Drosophila midgut as a model to demonstrate that the visceral musculature is disrupted by intrinsic and extrinsic factors, such as aging, feeding, chemical-induced tissue damage, and oncogenic transformation in the epithelium. Notably, we define four prominent visceral musculature disruption phenotypes, which we refer as ‘sprout’, ‘discontinuity’, ‘furcation’, and ‘crossover’ of the longitudinal muscle. Given that the occurrence of these phenotypes is increased during aging and under various stresses, we propose that these phenotypes can be used as quantitative readouts of deterioration of the visceral musculature. Intriguingly, administration of a tissue-damaging chemical dextran sulfate sodium (DSS) induced similar visceral musculature disruption phenotypes in zebrafish larvae, indicating that ingestion of a tissue-damaging chemical can disrupt the visceral musculature in a vertebrate as well. Our study provides insights into the deterioration of the gut visceral musculature and lays a groundwork for investigating the underlying mechanisms in Drosophila as well as other animals.
Comparative analysis of mandible morphology in four ant species with different foraging and nesting habits
Authors: Chowdhury Ritabrata , Rastogi Neelkamal 
Published: August 2021

ABSTRACTMandibles of ants can be considered as one of the most vital tools for the survival and success of their colonies since these are extensively utilised for defence, nest maintenance and foraging activities. We hypothesised that mandibular design is strongly dependent on the respective ecological niche and foraging habit of an ant species. In the present study, we compared the external morphology and zinc content in the mandibles of four species of ants by using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The ant mandible morphology varied significantly in accordance with their species-specific foraging and nesting strategies. The sickle-shaped mandibles of the strongly predaceous,Oecophylla smaragdinaworker ants were characterised by a large number of pointed teeth which would be of immense utility for subduing the prey, while the shovel-shaped, highly sclerotized mandibles ofCataglyphus longipedemants appear to be adaptations for the solitary scavenging habit and nest maintenance in arid habitats. The large-sized mandibles ofCamponotus compressusants and the stout mandibles of the predatory,Tetraponera. rufonigraforager ants, have apparently evolved for collection of sugary secretions by the former and for the solitary foraging and arboreal nesting habit of the latter. The mandibular zinc content was highest inT. rufonigraants and the lowest in the mandibles of the sugar-lovingCm. compressusants. The diversity in the arrangement of bristles and the type of mandibular concavities, have also evolved accordingly. Thus, this study might prove to be instrumental in evaluating the various physical mechanisms involved in the evolution of insect mandibles for their defined function.
MRI-Visible Perivascular Space (PVS) Changes with Long-Duration Spaceflight
Authors: Hupfeld Kathleen E. , Richmond Sutton B. , McGregor Heather R. , Schwartz Daniel L. , Luther Madison , Beltran Nichole E. , Kofman Igor S. , De Dios Yiri E. , Riascos Roy F. , Wood Scott J. , Bloomberg Jacob J. , Mulavara Ajitkumar P. , Silbert Lisa , Iliff Jeffrey J. , Seidler Rachael D. , Piantino Juan 
Published: August 2021

AbstractHumans are exposed to extreme environmental stressors during spaceflight and return with alterations in brain structure and shifts in intracranial fluids. To date, no studies have evaluated the effects of spaceflight on perivascular spaces (PVSs) within the brain, which are believed to facilitate fluid drainage and brain homeostasis. Here, we examined how the number and morphology of magnetic resonance imaging (MRI)-visible PVSs are affected by spaceflight, including prior spaceflight experience. Fifteen astronauts underwent sixT1-weighted 3T MRI scans, twice prior to launch and four times following their return to Earth after ∼6-month missions to the International Space Station. White matter MRI-visible PVS number and morphology were calculated using an established automated segmentation algorithm. We found that novice astronauts showed an increase in total PVS volume from pre- to post-flight, whereas experienced crewmembers did not (adjusted for age, sex, and time between landing and first MRI scan). Moreover, experienced astronauts exhibited a significant correlation between more previous flight days and greater PVS median length at baseline, suggesting that experienced astronauts exhibit holdover effects from prior spaceflight(s). There was also a significant positive correlation between pre- to post-flight increases in PVS median length and increases in right lateral ventricular volume. The presence of spaceflight associated neuro-ocular syndrome (SANS) was not associated with PVS number or morphology. Together, these findings demonstrate that spaceflight is associated with PVS morphological changes, and specifically that spaceflight experience is an important factor in determining PVS characteristics.
LESSONS FROM THE COVID-19 THIRD WAVE IN CANADA: THE IMPACT OF VARIANTS OF CONCERN AND SHIFTING DEMOGRAPHICS
Authors: McAlister Finlay A. , Nabipoor Majid , Chu Anna , Lee Douglas S. , Saxinger Lynora , Bakal Jeffrey A. 
Published: August 2021

ABSTRACTImportanceWith the emergence of more transmissible SARS-CoV-2 variants of concern (VOC), there is an urgent need for evidence about disease severity and the health care impacts of VOC in North America, particularly since a substantial proportion of the population have declined vaccination thus far.ObjectiveTo examine 30-day outcomes in Canadians infected with SARS-CoV-2 in the first year of the pandemic and to compare event rates in those with VOC versus wild-type infection.DesignRetrospective cohort study using linked healthcare administrative datasets.SettingAlberta and Ontario, the two Canadian provinces that experienced the largest third wave in the spring of 2021.ParticipantsAll individuals with a positive SARS-CoV-2 reverse transcriptase polymerase chain reaction swab from March 1, 2020 until March 31, 2021, with genomic confirmation of VOC screen-positive tests during February and March 2021 (wave 3).Exposure of InterestVOC versus wild type SARS-CoV-2Main Outcomes and MeasuresAll-cause hospitalizations or death within 30 days after a positive SARS-CoV-2 swab.ResultsCompared to the 372,741 individuals with SARS-CoV-2 infection between March 2020 and January 2021 (waves 1 and 2 in Canada), there was a shift in transmission towards younger patients in the 104,232 COVID-19 cases identified in wave 3. As a result, although third wave patients were more likely to be hospitalized (aOR 1.34 [1.29-1.39] in Ontario and aOR 1.53 [95%CI 1.41-1.65] in Alberta), they had shorter lengths of stay (median 5 vs. 7 days, p<0.001) and were less likely to die within 30 days (aOR 0.66 [0.60-0.71] in Ontario and aOR 0.74 [0.62-0.89] in Alberta). However, within the third wave, patients infected with VOC (91% Alpha) exhibited higher risks of death (aOR 1.52 [1.27-1.81] in Ontario and aOR 1.67 [1.13-2.48] in Alberta) and hospitalization (aOR 1.57 [1.47-1.69] in Ontario and aOR 1.88 [1.74-2.02] in Alberta) than those with wild-type SARS-CoV-2 infections during the same timeframe.Conclusions and RelevanceOn a population basis, the shift towards younger age groups as the COVID-19 pandemic has evolved translates into more hospitalizations but shorter lengths of stay and lower mortality risk than seen in the first 10 months of the pandemic in Canada. However, on an individual basis, infection with a VOC is associated with a higher risk of hospitalization or death than the original wild-type SARS-CoV-2 – this is important information to address vaccine hesitancy given the increasing frequency of VOC infections now.
Host lung environment limits Aspergillus fumigatus germination through a SskA-dependent signaling response
Authors: Kirkland Marina E. , Stannard McKenzie , Kowalski Caitlin H. , Mould Dallas , Caffrey-Carr Alayna , Temple Rachel M. , Ross Brandon S. , Lofgren Lotus A. , Stajich Jason E. , Cramer Robert A. , Obar Joshua J. 
Published: August 2021

ABSTRACTAspergillus fumigatus isolates display significant heterogeneity in growth, virulence, pathology, and inflammatory potential in multiple murine models of invasive aspergillosis. Previous studies have linked the initial germination of a fungal isolate in the airways to the inflammatory and pathological potential; but the mechanism(s) regulating A. fumigatus germination in the airways are unresolved. To explore the genetic basis for divergent germination phenotypes, we utilized a serial passaging strategy in which we cultured a slow germinating strain (AF293) in a murine lung based medium for multiple generations. Through this serial passaging approach, a strain emerged with an increased germination rate that induces more inflammation than the parental strain (herein named Lung Homogenate Evolved (LH-EVOL)). We identified a potential loss of function allele of Afu5g08390 (sskA) in the LH-EVOL strain. The LH-EVOL strain had a decreased ability to induce the SakA-dependent stress pathway, similar to AF293 ΔsskA and CEA10. In support of the whole genome variant analyses, sskA, sakA, or mpkC loss of function strains in the AF293 parental strain increased germination both in vitro and in vivo. Since the airway surface liquid of the lungs contains low glucose levels, the relationship of low glucose concentration on germination of these mutant AF293 strains was examined; interestingly, in low glucose conditions the sakA pathway mutants exhibited an enhanced germination rate. In conclusion, A. fumigatus germination in the airways is regulated by SskA through the SakA MAPK pathway and drives enhanced disease initiation and inflammation in the lungs.IMPORTANCEAspergillus fumigatus is an important human fungal pathogen particularly in immunocompromised individuals. Initiation of growth by A. fumigatus in the lung is important for its pathogenicity in murine models. However, our understanding of what regulates fungal germination in the lung environment is lacking. Through a serial passage experiment using lung-based medium, we identified a new strain of A. fumigatus which has increased germination potential and inflammation in the lungs. Using this serially passaged strain we found it had a decreased ability to mediate signaling through the osmotic stress response pathway. This finding was confirmed using genetic null mutants demonstrating that the osmotic stress response pathway is critical for regulating growth in the murine lungs. Our results contribute to the understanding of A. fumigatus adaptation and growth in the host lung environment.
The STAT5-IRF4-BATF pathway drives heightened epigenetic remodeling in naïve CD4+T cell responses of older adults
Authors: Zhang Huimin , Jadhav Rohit R. , Cao Wenqiang , Goronzy Isabel N. , Jin Jun , Greenleaf William J. , Weyand Cornelia M. , Goronzy Jörg J. 
Published: August 2021

SummaryT cell aging is a complex process combining the emergence of cellular defects with activation of adaptive mechanisms. Generation of T cell memory is impaired, while a low-inflammatory state is induced, in part due to effector T cells. To determine whether age-associated changes in T cell fate decisions occur early after T cell activation, we profiled the longitudinal transcriptional and epigenetic landscape induced by TCR stimulation comparing naïve CD4+T cells from young and older adults. In spite of attenuated TCR signaling, activation-induced remodeling of the epigenome increased with age, culminating in heightened BATF and BLIMP1 activity. Single cell studies, integrating ATAC-seq and RNA-seq data, identified increases in dysfunctional and in effector T cells and a decrease in BACH2-expressing memory cell precursors. STAT5 activation, in part due to a decline in HELIOS and aberrant IL-2 receptor expression, accounted for the induction of transcription factor networks favoring effector cell differentiation.
Advanced Age Has Dissociable Effects on Hippocampal CA1 and CA3 Ripples
Authors: DiCola Nicholas M. , Lacy Alexa L. , Bishr Omar J. , Kimsey Kathryn M. , Whitney Jenna L. , Lovett Sarah D. , Burke Sara N. , Maurer Andrew P. 
Published: August 2021

ABSTRACTSharp-wave/ripples are brief, high-frequency events in hippocampal subregions CA3 and CA1 that occur during rest or pauses in behavior. Ripples detected in CA1 have lower frequency in aged compared to young rats. Although CA1 ripples are theorized to manifest from CA3, ripple dynamics in CA3 have not been examined in aged animals. The current study obtained simultaneous recordings between CA1 and CA3 in young and aged rats to examine sharp-wave/ripple characteristics in both regions in relation to age. While CA1 ripple frequency was reduced with age, there were no age differences in CA3 ripples. In aged, but not young, rats there was also a significant increase in the probability of CA3 and CA1 ripples co-occurring between the pre- and post-behavior rest epochs. Moreover, in both age groups, CA1 ripples that co-occurred with a CA3 ripple had increased frequency, power, and duration. These findings suggest age differences in CA1 are not due to altered afferent input from CA3, but instead reflect distinct mechanisms of ripple generation with age.HIGHLIGHTSCA1 ripple frequency is reduced with age.CA3 ripple characteristics do not change with age.In aged rats only, CA3-CA1 ripple co-occurrence increased following behavior.CA1 ripples that co-occurred with CA3 had greater frequency, power, and duration.
Data-driven, participatory characterization of farmer varieties discloses teff breeding potential under current and future climates
Authors: Woldeyohannes Aemiro B. , Iohannes Sessen D. , Miculan Mara , Caproni Leonardo , Ahmed Jemal S. , de Sousa Kauê , Desta Ermias A. , Fadda Carlo , Pè Mario E. , Dell’Acqua Matteo 
Published: August 2021

AbstractIn smallholder farming systems, traditional farmer varieties of neglected and underutilized species (NUS) support the livelihoods of millions of growers and consumers. NUS combine cultural and agronomic value with local adaptation and transdisciplinary methods are needed to fully evaluate their breeding potential. Here, we assembled and characterized the genetic diversity of a representative collection of 366 Ethiopian teff (Eragrostis tef) farmer varieties and breeding materials, describing their phylogenetic relation and local adaptation on the Ethiopian landscape. We phenotyped the collection for its agronomic performance, involving local farmers expert teff growers in a participatory variety evaluation. Our analyses revealed environmental patterns of teff genetic diversity and allowed us to identify ten genetic clusters associated with climate variation and with uneven spatial distribution. A genome wide association study (GWAS) was used to identify loci and candidate genes related to phenology, yield, local adaptation, and farmers’ appreciation. The estimated teff genomic offset under climate change scenarios highlighted an area around lake Tana where teff cropping may be most vulnerable to climate change. Our results show that transdisciplinary approaches may efficiently propel untapped NUS farmer varieties into modern breeding to foster more resilient and sustainable cropping systems.
Benchmarking Computational Integration Methods for Spatial Transcriptomics Data
Authors: Li Yijun , Stanojevic Stefan , He Bing , Jing Zheng , Huang Qianhui , Kang Jian , Garmire Lana X. 
Published: August 2021

AbstractThe increasing popularity of spatial transcriptomics has allowed researchers to analyze transcriptome data in its tissue sample’s spatial context. Various methods have been developed for detecting SV (spatially variable) genes, with distinct spatial expression patterns. However, the accuracy of using these SV genes in clustering has not been thoroughly studied. On the other hand, in single cell resolution sequencing data without spatial context, clustering analysis is usually done on highly variable (HV) genes. Here we investigate if integrating SV genes and HV genes from spatial transcriptomics data can improve clustering performance beyond using SV genes alone. We examined three methods that detect SV genes, including Giotto, spatialDE, and SPARK, and evaluated six methods that integrate different features measured from the same samples including MOFA+, scVI, Seurat v4, CIMLR, SNF, and the straightforward concatenation approach. We applied these methods on 19 real datasets from three different spatial transcriptomics technologies (merFISH, SeqFISH+, and Visium) as well as 20 simulated datasets of varying spatial expression conditions. Our evaluations show that MOFA+ and simple concatenation have good performances in general, despite the variations among datasets and spatial transcriptomics platforms. This work shows that integrating highly variable and spatially variable genes in the spatial transcriptomics data can improve clustering beyond using spatially variable genes only. It also provides practical guides on the choices of computational methods to accomplish this goal.