bluuebunny/crossref_metadata_2025 huggingface dataset:
A Long-Amplicon Viability-qPCR Test for Quantifying Living Pathogens that Cause Bacterial Spot in Tomato Seed
Authors: Wang Hehe , Wagnon Rieanna , Moreno Daniela , Timilsina Sujan , Jones Jeffery , Vallad Gary , Turechek William W.
Published: December 2021

Bacterial spot is one of the most serious diseases of tomato. It is caused by four species of Xanthomonas: X. euvesicatoria, X. gardneri, X. perforans, and X. vesicatoria. Contaminated or infected seed can be a major source of inoculum for this disease. The use of certified pathogen-free seed is one of the primary management practices to reduce the inoculum load in commercial production. Current seed testing protocols rely mainly on plating the seed extract and conventional PCR; however, the plating method cannot detect viable but nonculturable cells, and the conventional PCR assay has limited capability to differentiate DNA extracted from viable or dead bacterial cells. To improve the sensitivity and specificity of the tomato seed testing method for bacterial spot pathogens, a long-amplicon quantitative PCR (qPCR) assay coupled with propidium monoazide (PMA-qPCR) was developed to quantify selectively the four pathogenic Xanthomonas species in tomato seed. The optimized PMA-qPCR procedure was evaluated on pure bacterial suspensions, bacteria-spiked seed extracts, and seed extracts of inoculated and naturally infected seed. A crude DNA extraction protocol also was developed, and PMA-qPCR with crude bacterial DNA extracts resulted in accurate quantification of 104 to 108 CFU/ml of viable bacteria when mixed with dead cells at concentrations as high as 107 CFU/ml in the seed extracts. With DNA purified from concentrated seed extracts, the PMA-qPCR assay was able to detect DNA of the target pathogens in seed samples spiked with ≥75 CFU/ml (about 0.5 CFU/seed) of the viable pathogens. Latent class analysis of the inoculated and naturally infected seed samples showed that the PMA-qPCR assay had greater sensitivity than plating the seed extracts on the semiselective modified Tween Medium B and CKTM media for all four target species. Being much faster and more sensitive than dilution plating, the PMA-qPCR assay has potential to be used as a standalone tool or in combination with the plating method to improve tomato seed testing and advance the production of clean seed.
A Method for Estimating the Deposition Density of Fallout on the Ground and on Vegetation from a Low-yield, Low-altitude Nuclear Detonation
Authors: Beck Harold L. , Bouville André , Simon Steven L. , Anspaugh Lynn R. , Thiessen Kathleen M. , Shinkarev Sergey , Gordeev Konstantin
Published: December 2021

This paper describes a relatively simple model developed from observations of local fallout from US and USSR nuclear tests that allows reasonable estimates to be made of the deposition density (activity per unit area) on both the ground and on vegetation for each radionuclide of interest produced in a nuclear fission detonation as a function of location and time after the explosion. In addition to accounting for decay rate and in-growth of radionuclides, the model accounts for the fractionation (modification of the relative activity of various fission and activation products in fallout relative to that produced in the explosion) that results from differences in the condensation temperatures of the various fission and activation products produced in the explosion. The proposed methodology can be used to estimate the deposition density of all fallout radionuclides produced in a low yield, low altitude fission detonation that contribute significantly to dose. The method requires only data from post-detonation measurements of exposure rate (or beta or a specific nuclide activity) and fallout time-of-arrival. These deposition-density estimates allow retrospective as well as rapid prospective estimates to be made of both external and internal radiation exposure to downwind populations living within a few hundred kilometers of ground zero, as described in the companion papers in this volume.
Dose Coefficients for Internal Dose Assessments for Exposure to Radioactive Fallout
Authors: Melo Dunstana R. , Bertelli Luiz , Ibrahim Shawki A. , Anspaugh Lynn R. , Bouville André , Simon Steven L.
Published: December 2021

This paper presents values as well as the bases for calculating internal dose coefficients suitable for estimating organ doses from the exposure to radioactive fallout that could result from the detonation of a nuclear fission device. The 34 radionuclides discussed are the same as those given in a priority list of radionuclides for fallout dose assessments presented in a companion overview paper. The radionuclides discussed are those that are believed to account for a preponderance of the organ doses that might be received by intake by persons of all ages (including in utero and via breast feeding for infants) following exposure to radioactive fallout. The presented dose coefficients for ingestion account for age and include modifications for variations in solubility with distance as discussed previously in the literature, and those for inhalation similarly account for age, solubility, and particle sizes that would be relevant at various distances of exposure as discussed in a companion paper on ingestion dose methods. The proposed modifications peculiar to radioactive fallout account for systematic changes in solubility and particle sizes with distance from the site of detonation, termed here as the region of “local fallout” and the region “beyond local fallout.” Brief definitions of these regions are provided here with more detailed discussion in a companion paper on estimating deposition of fallout radionuclides. This paper provides the dose coefficients for ingestion and inhalation (for particle sizes of 1 μm, 5 μm, 10 μm, and 20 μm) for the region “local fallout.” These dose coefficients for “local fallout” are specific for particles formed in a nuclear explosion that can be large and have radionuclides, particularly the more refractory ones, distributed throughout the volume where the radionuclide has reduced solubility. The dose coefficients for the region “beyond local fallout” are assumed to be the ones published by the International Commission on Radiological Protection (ICRP) in 1995. Comparisons of the presented dose coefficients are made with values published by the ICRP.
Speech Development in Cleft Palate with and without Robin Sequence
Authors: Naros Andreas , Bartel Sylva , Bacher Margit , Koos Bernd , Blumenstock Gunnar , Wiechers Cornelia , Poets Christian F. , Reinert Siegmar , Krimmel Michael
Published: December 2021

Background:

Robin sequence is defined as the triad of micrognathia, glossoptosis, and upper airway obstruction. In up to 85 percent, it is associated with cleft palate. Many studies have reported worse speech development in Robin sequence children after cleft palate repair. The authors investigated speech development in isolated Robin sequence with cleft palate versus children with cleft palate only at the age of 5 to 6 years.

Methods:

All Robin sequence children were treated with the Tübingen palatal plate after birth. Data were collected using the German version of the Great Ormond Street Speech Assessment. Audio and video recordings were reviewed and analyzed separately by two blinded senior phoniatricians based on the German version of the Universal Reporting Parameters for Cleft Palate Speech, and scored to enable comparability of speech outcomes.

Results:

Forty-four children (Robin sequence, n = 22; cleft palate only, n = 22) were included. Robin sequence children were significantly older at surgery (11.8 months versus 7.1 months; p < 0.001) but younger at study (70.5 months versus 75.2 months; p = 0.035). They also had more severe cleft of the palate (p = 0.006). All children studied showed good to very good speech development without serious impairment. None of the reported parameters on the German version of the Universal Reporting Parameters for Cleft Palate Speech showed significant group differences; the median total score in the Robin sequence group was 23 (interquartile range, 16.5 to 27.5) versus 19 (interquartile range, 17 to 23) in the cleft palate–only group. Statistical analysis revealed no significant effect of group (Z = −1.47; p = 0.14).

Conclusions:

No group differences in speech development were found at age 5 to 6 years. Isolated Robin sequence does not necessarily represent a risk for impaired speech development.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Risk, II.
Use of Erythropoietin and Fibrin Glue Mixture for Peripheral Nerve Repair
Authors: Erdal Ayhan Işik , Findikçioğlu Kemal , Karasu Oğuzhan , Özkoçer Süheyla Esra , Elmas Çiğdem
Published: December 2021

Background:

Erythropoietin has neuroregenerative effects. Fibrin glue may be used for nerve repair and controlled release of substances. In this study, the authors investigated the effects of erythropoietin-containing fibrin glue on nerve repair, based on the hypothesis that erythropoietin-containing fibrin glue would positively affect nerve regeneration.

Methods:

Thirty-six Long-Evans rats were used. The animals were divided into six groups. Their left sciatic nerves were isolated, transected, and repaired with saline-containing fibrin glue in group 1, with erythropoietin-containing fibrin glue in group 2, with saline-containing fibrin glue and two sutures in group 3, with erythropoietin-containing fibrin glue and two sutures in group 4, with two sutures in group 5, and with four sutures in group 6. Sciatic Functional Index calculation, pin-prick test, and toe-spread test were performed on days 21, 42, and 63. All animals were killed on day 63. The nerve sections were analyzed histologically.

Results:

The Sciatic Functional Index, pin-prick test, and toe-spread test results were the best in group 4 and the worst in group 5. Group 4 showed superior Schwann cell proliferation (p < 0.05). Groups with epineural suture use (groups 3, 4, 5, and 6) had higher endoneurial collagen synthesis scores than the groups without suture use (groups 1 and 2) (p < 0.05). The myelin protein zero immunostaining results were significantly higher in the erythropoietin-treated groups (groups 2 and 4) (p < 0.05).

Conclusion:

The combined use of erythropoietin-containing fibrin glue and two epineural sutures (group 4) showed a statistically significant improvement in many parameters.

Clinical Relevance Statement:

Fibrin glue is already used in nerve repair. Adding erythropoietin to fibrin glue could be a safe and easy option to improve nerve regeneration.
Collective minds: social network topology shapes collective cognition
Authors: Momennejad Ida
Published: December 2021

Human cognition is not solitary, it is shaped by collective learning and memory. Unlike swarms or herds, human social networks have diverse topologies, serving diverse modes of collective cognition and behaviour. Here, we review research that combines network structure with psychological and neural experiments and modelling to understand how the topology of social networks shapes collective cognition. First, we review graph-theoretical approaches to behavioural experiments on collective memory, belief propagation and problem solving. These results show that different topologies of communication networks synchronize or integrate knowledge differently, serving diverse collective goals. Second, we discuss neuroimaging studies showing that human brains encode the topology of one's larger social network and show similar neural patterns to neural patterns of our friends and community ties (e.g. when watching movies). Third, we discuss cognitive similarities between learning social and non-social topologies, e.g. in spatial and associative learning, as well as common brain regions involved in processing social and non-social topologies. Finally, we discuss recent machine learning approaches to collective communication and cooperation in multi-agent artificial networks. Combining network science with cognitive, neural and computational approaches empowers investigating how social structures shape collective cognition, which can in turn help design goal-directed social network topologies.

This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.
Collective knowledge and the dynamics of culture in chimpanzees
Authors: Whiten Andrew , Harrison Rachel A. , McGuigan Nicola , Vale Gillian L. , Watson Stuart K.
Published: December 2021

Social learning in non-human primates has been studied experimentally for over 120 years, yet until the present century this was limited to what one individual learns from a single other. Evidence of group-wide traditions in the wild then highlighted the collective context for social learning, and broader ‘diffusion experiments’ have since demonstrated transmission at the community level. In the present article, we describe and set in comparative perspective three strands of our recent research that further explore the collective dimensions of culture and cumulative culture in chimpanzees. First, exposing small communities of chimpanzees to contexts incorporating increasingly challenging, but more rewarding tool use opportunities revealed solutions arising through the combination of different individuals' discoveries, spreading to become shared innovations. The second series of experiments yielded evidence of conformist changes from habitual techniques to alternatives displayed by a unanimous majority of others but implicating a form of quorum decision-making. Third, we found that between-group differences in social tolerance were associated with differential success in developing more complex tool use to exploit an increasingly inaccessible resource. We discuss the implications of this array of findings in the wider context of related studies of humans, other primates and non-primate species.

This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.
Artificial evolution of robot bodies and control: on the interaction between evolution, learning and culture
Authors: Hart Emma , Le Goff Léni K.
Published: December 2021

We survey and reflect on how learning (in the form of individual learning and/or culture) can augment evolutionary approaches to the joint optimization of the body and control of a robot. We focus on a class of applications where the goal is to evolve the body and brain of a single robot to optimize performance on a specified task. The review is grounded in a general framework for evolution which permits the interaction of artificial evolution acting on a population with individual and cultural learning mechanisms. We discuss examples of variations of the general scheme of ‘evolution plus learning’ from a broad range of robotic systems, and reflect on how the interaction of the two paradigms influences diversity, performance and rate of improvement. Finally, we suggest a number of avenues for future work as a result of the insights that arise from the review.

This article is part of a discussion meeting issue ‘The emergence of collective knowledge and cumulative culture in animals, humans and machines’.
Unique roles of vaginal Megasphaera phylotypes in reproductive health
Authors: Glascock Abigail L. , Jimenez Nicole R. , Boundy Sam , Koparde Vishal N. , Brooks J. Paul , Edwards David J. , Strauss III Jerome F. , Jefferson Kimberly K. , Serrano Myrna G. , Buck Gregory A. , Fettweis Jennifer M.
Published: December 2021

The composition of the human vaginal microbiome has been extensively studied and is known to influence reproductive health. However, the functional roles of individual taxa and their contributions to negative health outcomes have yet to be well characterized. Here, we examine two vaginal bacterial taxa grouped within the genus

Megasphaera

that have been previously associated with bacterial vaginosis (BV) and pregnancy complications. Phylogenetic analyses support the classification of these taxa as two distinct species. These two phylotypes,

Megasphaera

phylotype 1 (MP1) and

Megasphaera

phylotype 2 (MP2), differ in genomic structure and metabolic potential, suggestive of differential roles within the vaginal environment. Further, these vaginal taxa show evidence of genome reduction and changes in DNA base composition, which may be common features of host dependence and/or adaptation to the vaginal environment. In a cohort of 3870 women, we observed that MP1 has a stronger positive association with bacterial vaginosis whereas MP2 was positively associated with trichomoniasis. MP1, in contrast to MP2 and other common BV-associated organisms, was not significantly excluded in pregnancy. In a cohort of 52 pregnant women, MP1 was both present and transcriptionally active in 75.4 % of vaginal samples. Conversely, MP2 was largely absent in the pregnant cohort. This study provides insight into the evolutionary history, genomic potential and predicted functional role of two clinically relevant vaginal microbial taxa.
Genetic differentiation of Xylella fastidiosa following the introduction into Taiwan
Authors: Castillo Andreina I. , Tsai Chi-Wei , Su Chiou-Chu , Weng Ling-Wei , Lin Yu-Chen , Cho Shu-Ting , Almeida Rodrigo P. P. , Kuo Chih-Horng
Published: December 2021

The economically important plant pathogen

Xylella fastidiosa

has been reported in multiple regions of the globe during the last two decades, threatening a growing list of plants. Particularly,

X. fastidiosa

subspecies

fastidiosa

causes Pierce’s disease (PD) of grapevines, which is a problem in the USA, Spain, and Taiwan. In this work, we studied PD-causing subsp. fastidiosa populations and compared the genome sequences of 33 isolates found in Central Taiwan with 171 isolates from the USA and two from Spain. Phylogenetic relationships, haplotype networks, and genetic diversity analyses confirmed that subsp. fastidiosa was recently introduced into Taiwan from the Southeast USA (i.e. the PD-I lineage). Recent core-genome recombination events were detected among introduced subsp. fastidiosa isolates in Taiwan and contributed to the development of genetic diversity. The genetic diversity observed includes contributions through recombination from unknown donors, suggesting that higher genetic diversity exists in the region. Nevertheless, no recombination event was detected between

X. fastidiosa

subsp.

fastidiosa

and the endemic sister species

Xylella taiwanensis

, which is the causative agent of pear leaf scorch disease. In summary, this study improved our understanding of the genetic diversity of an important plant pathogenic bacterium after its invasion to a new region.
Identification of a shared, common haplotype cosegregating with an SGCB c.544A>C mutation in Indian patients affected with sarcoglycanopathy
Authors: Sanga Shamita , Chakraborty Sudipta , Bardhan Mainak , Nalini Atchayaram , Acharya Moulinath
Published: December 2021

Background

Sarcoglycanopathies (SG) is the most frequent form of autosomal recessive limb-girdle muscular dystrophies (LGMD) leading to progressive muscle wasting and weakness, predominantly characterized by limb-girdle weakness. LGMDR4 is caused by mutations in SGCB encoding for the beta-sarcoglycan proteins. In this study, we describe a shared, common haplotype cosegregating in 14 SG cases from 13 unrelated families with the likely pathogenic homozygous mutation c.544A>C (p.Thr182Pro) in SGCB.

Methods

The genotypes of five selected markers (rs10009426, rs6824707, rs2271046, rs35414474 and rs17611952) surrounding the c.544A>C (p.Thr182Pro) were extracted from the variant call format (VCF) generated from whole-exome sequencing (WES) of 14 cases and 14 related family members as controls. The linkage data file was constructed and linkage disequilibrium (LD) plots were generated using HaploView to visualize patterns of LD. Further, haplotype reconstructions based on the 6 markers were conducted using PLINK1.9. using the expectation-maximization (EM) algorithm, an iterative method to find maximum likelihood. Subsequently, the R programming language was used to determine and compare plots of the haplotype frequencies and percentages for both groups to infer the risk haplotypes.

Results

Four strong LD blocks were identified in control group: rs10009426 to rs6824707 (0.27□kb), rs6824707 to rs2271046 (41.6 kb), rs10009426 to rs2271046 (41.8 kb) and rs35414474 to rs17611952 (0.17 kb) which were absent in the case group. Similarly, a total of nine haplotypes were estimated in cases and controls of which haplotype H1= G, A, T, G, G, T showed significant statistical difference in the frequency between cases and controls. H1 is also observed to cosegregate with c.544A>C (p.Thr182Pro) in the pedigrees of all the cases.

Conclusion

The identification of c.544A>C (p.Thr182Pro) mutation in 14 cases from India indicates a probable event of founder effect. Further, the H1 haplotype, cosegregating with this mutation, convincingly sheds light on the recent developments in population genetics allowing insights into demographic and population history. This haplotype can also be used as a genetic marker to screen individuals with genetic susceptibility as carriers and provide genetically informed risk stratification and management in the prevention of SG.
Clinical implementation and initial experience with a 1.5 Tesla MR-linac for MR-guided radiotherapy for gynecologic cancer: An R-IDEAL stage 1/2a first in humans/feasibility study of new technology implementation
Authors: Lakomy David S. , Yang Jinzhong , Vedam Sastry , Wang Jihong , Lee Belinda , Sobremonte Angela , Castillo Pamela , Hughes Neil , Mohammadsaid Mustefa , Jhingran Anuja , Klopp Ann H. , Choi Seungtaek , Fuller C. David , Lin Lilie L.
Published: December 2021

Purpose

Magnetic resonance imaging–guided linear accelerator systems (MR-linacs) can facilitate the daily adaptation of radiotherapy plans. Here, we report our early clinical experience using an MR-linac for adaptive radiotherapy of gynecologic malignancies.

Methods and Materials

Treatments were planned with an Elekta Monaco v5.4.01 and delivered by a 1.5 Tesla Elekta Unity MR-linac. The system offers a choice of daily adaptation based on either position (ATP) or shape (ATS) of the tumor and surrounding normal structures. The ATS approach has the option of manually editing the contours of tumors and surrounding normal structures before the plan is adapted. Here we documented the duration of each treatment fraction; set-up variability (assessed by isocenter shifts in each plan) between fractions; and, for quality assurance, calculated the percentage of plans meeting the y-criterion of 3%/3-mm distance to agreement. Deformable accumulated dose calculations were used to compare ATP plans with reference dose plans.

Results

Of the 10 patients treated with 90 fractions on the MR-linac, most received boost doses to recurrence in nodes or isolated tumors. Each treatment fraction lasted a median 32 minutes; fractions were shorter with ATP than with ATS (30 min vs 42 min, P<0.0001). The y criterion for all fraction plans exceeded >90% (median 99.9%, range 92.4%–100%), i.e., all plans passed quality assurance testing. The average extent of isocenter shift was <0.5 cm in each axis. The accumulated dose to the gross tumor volume was within 10% of the reference plan for all ATP cases. Accumulated doses for lesions in the pelvic periphery were within 1% of the reference plan as opposed to –5.8% to –9.6% for central tumors.

Conclusions

The MR-linac is a reliable and clinically feasible tool for treating patients with gynecologic cancer.
Genome, proteome, and immunome data explain why 6 month controlled human malaria infection with sporozoites of the Pf7G8 clone of Plasmodium falciparum is a rigorous predictor of the efficacy of the PfNF54-based PfSPZ Vaccine in Africa
Authors: Silva Joana C. , Dwivedi Ankit , Moser Kara A. , Sissoko Mahamadou S. , Epstein Judith E. , Healy Sara A. , Lyke Kirsten E. , Mordmüller Benjamin , Kremsner Peter G. , Duffy Patrick E. , Murshedkar Tooba , Lee Sim B. Kim , Richie Thomas L. , Hoffman Stephen L.
Published: December 2021

Controlled human malaria infection (CHMI) has supported Plasmodium falciparum (Pf) malaria vaccine development by providing preliminary estimates of vaccine efficacy (VE). Because CHMIs generally use Pf strains similar to vaccine strains, VE against antigenically heterogeneous Pf in the field has been required to establish VE. We increased the stringency of CHMI by selecting a Brazilian isolate, Pf7G8, which is genetically distant from the West African parasite (PfNF54) in our PfSPZ vaccines. Using two regimens to identically immunize US and Malian adults, VE over 24 weeks in the field was as good as or better than against CHMI at 24 weeks in the US. To explain this finding, we quantified differences in the genome, proteome and predicted CD8 T cell epitopes of PfNF54 relative to 709 Pf isolates from Africa and Pf7G8. Pf7G8 is more distant from PfNF54 than any African isolates tested. We propose VE against Pf7G8 CHMI for providing pivotal data for malaria vaccine licensure for travelers to Africa, and potentially for endemic populations, because the genetic distance of Pf7G8 from the Pf vaccine strain makes it a stringent surrogate for Pf parasites in Africa.
Patients with benign breast disease and breast cancer need more COVID-19 vaccines
Authors: Wu Huai-liang , He Zong-lin , Gong Yue , Mo Miao , Liu Guang-yu
Published: December 2021

Albeit the efficacy of COVID-19 vaccines in immunocompromised patients is undermined, it is still found beneficial. Patients with cancer have a much lower COVID-19 vaccination rate globally, and the vaccination coverage in breast cancer patients in China remains elusive. A total of 23029 patients with benign breast diseases and breast cancers were included in the study, and the vaccination rates of patients with benign breast tumors and other benign breast diseases, nonmetastatic and metastatic breast cancer were 44.0%, 54.7%, 19.2% and 9.6%, respectively. Breast cancer in situ patients had a similar vaccination rate with patients with benign breast tumors (45.9% vs 44.0%) while those with invasive breast cancer had much lower vaccination rates. The overall vaccination rate remains meager in breast cancer patients, and gap was found in patients with lower clinical stage. Hence vaccination should be further promoted among patients with benign breast diseases and breast cancer.
ClusTRace, a bioinformatic pipeline for analyzing clusters in virus phylogenies
Authors: Plyusnin Ilya , Nguyen Phuoc Thien Truong , Sironen Tarja , Vapalahti Olli , Smura Teemu , Kant Ravi
Published: December 2021

SARS-CoV-2 is the highly transmissible etiologic agent of coronavirus disease 2019 (COVID-19) and has become a global scientific and public health challenge since December 2019. Several new variants of SARS-CoV-2 have emerged globally raising concern about prevention and treatment of COVID-19. Early detection and in depth analysis of the emerging variants allowing pre-emptive alert and mitigation efforts are thus of paramount importance.

Here we present ClusTRace, a novel bioinformatic pipeline for a fast and scalable analysis of sequence clusters or clades in large viral phylogenies. ClusTRace offers several high level functionalities including outlier filtering, aligning, phylogenetic tree reconstruction, cluster or clade extraction, variant calling, visualization and reporting. ClusTRace was developed as an aid for COVID-19 transmission chain tracing in Finland and the main emphasis has been on fast and unsupervised screening of phylogenies for markers of super-spreading events and other features of concern, such as high rates of cluster growth and/or accumulation of novel mutations.

Availability

All code is freely available fromhttps://bitbucket.org/plyusnin/clustrace/
robustica: customizable robust independent component analysis
Authors: Anglada-Girotto Miquel , Miravet-Verde Samuel , Serrano Luis , Head Sarah A.
Published: December 2021

Background

Independent Component Analysis (ICA) allows the dissection of omic datasets into modules that help to interpret global molecular signatures. The inherent randomness of this algorithm can be overcome by clustering many iterations of ICA together to obtain robust components. Existing algorithms for robust ICA are dependent on the choice of clustering method and on computing a potentially biased and large Pearson distance matrix.

Results

We presentrobustica, a Python-based package to compute robust independent components with a fully customizable clustering algorithm and distance metric. Here, we exploited its customizability to revisit and optimize robust ICA systematically. From the 6 popular clustering algorithms considered,DBSCANperformed the best at clustering independent components across ICA iterations. After confirming the bias introduced with Pearson distances, we created a subroutine that infers and corrects the components’ signs across ICA iterations to enable using Euclidean distance. Our subroutine effectively corrected the bias while simultaneously increasing the precision, robustness, and memory efficiency of the algorithm. Finally, we show the applicability ofrobusticaby dissecting over 500 tumor samples from low-grade glioma (LGG) patients, where we define a new gene expression module with the key modulators of tumor aggressiveness downregulated uponIDH1mutation.

Conclusion

robusticabrings precise, efficient, and customizable robust ICA into the Python toolbox. Through its customizability, we explored how different clustering algorithms and distance metrics can further optimize robust ICA. Then, we showcased howrobusticacan be used to discover gene modules associated with combinations of features of biological interest. Taken together, given the broad applicability of ICA for omic data analysis, we envisionrobusticawill facilitate the seamless computation and integration of robust independent components in large pipelines.

Contact

miquel.anglada@crg.eu
Plant morphometry matches beetle diversity: effects of natural adjacent vegetation on grain Amaranth crop under small-holder conditions
Authors: Álvarez Hugo Alejandro , Clemente-Orta Gemma , Carrillo-Ruiz Hortensia , López-Olguín Jesús F. , Jiménez-García Daniel , Morón Miguel A.
Published: December 2021

Grain Amaranth, Amaranthus hypochondriacus L., is an emerging arable crop cultivated worldwide. One way to obtain resources from the crop, other than grain, is to grow Amaranths in the dry season and harvest only the leaves. In this environmental condition the response of an Amaranth agroecosystem to the presence of natural and semi-natural habitats or other crops has not been studied yet. We analysed the response of (1) Amaranth morphometry and (2) alpha and beta diversity of beetles to the nearness of adjacent vegetation and natural habitats (such as deciduous forest) at the small-holder conditions. Our results showed that A. hypochondriacus crop plants responded positively to the presence of an ecotone (adjacent vegetation) and the natural habitat (deciduous forest), i.e., A. hypochondriacus plants grew bigger in the section nearest to adjacent vegetation, which was a pattern consistent in time. Moreover, for beetles (considered as a bioindicator group), richness was different amongst the study areas and negatively followed the gradient of perturbation. These results suggest that Amaranth crop is sensitive to the presence of natural and semi-natural habitats but not to other crops in the dry season. In addition, beetles match the response of Amaranth plants. This is the first time that this type of data is recorded in grain Amaranth agroecosystem and it will help to understand the interaction amongst grain Amaranth agroecosystems, biodiversity, and natural adjacent vegetation to boost ecosystem services.
High-speed, multi-Z confocal microscopy for voltage imaging in densely labeled neuronal populations
Authors: Weber Timothy D. , Moya Maria V. , Mertz Jerome , Economo Michael N.
Published: December 2021

Genetically encoded voltage indicators (GEVIs) hold great promise for monitoring neuronal population activity, but GEVI imaging in dense neuronal populations remains difficult due to a lack of contrast and/or speed. To address this challenge, we developed a novel confocal microscope that allows simultaneous multiplane imaging with high-contrast at near-kHz rates. This approach enables high signal-to-noise ratio voltage imaging in densely labeled populations and minimizes optical crosstalk during concurrent optogenetic photostimulation.
Predicting proprioceptive cortical anatomy and neural coding with topographic autoencoders
Authors: Grogan Max , Blum Kyle P. , Wu Yufei , Harston J. Alex , Miller Lee E. , Aldo Faisal A.
Published: December 2021

Proprioception is one of the least understood senses, yet fundamental for the control of movement. Even basic questions of how limb pose is represented in the somatosensory cortex are unclear. We developed a topographic variational autoencoder with lateral connectivity (topo-VAE) to compute a putative cortical map from a large set of natural movement data. Although not fitted to neural data, our model reproduces two sets of observations from monkey centre-out reaching: 1. The shape and velocity dependence of proprioceptive receptive fields in hand-centered coordinates despite the model having no knowledge of arm kinematics or hand coordinate systems. 2. The distribution of neuronal preferred directions (PDs) recorded from multi-electrode arrays. The model makes several testable predictions: 1. Encoding across the cortex has a blob-and-pinwheel-type geometry of PDs. 2. Few neurons will encode just a single joint. Our model provides a principled basis for understanding of sensorimotor representations, and the theoretical basis of neural manifolds, with applications to the restoration of sensory feedback in brain-computer interfaces and the control of humanoid robots.

Author Summary

It is well established that proprioception is essential for effective for motor control, yet our understanding of proprioceptive coding in somatosensory cortex is far behind that of more established sensory modalities such as vision and touch. Here, we use unsupervised learning of a deep neural network imposed with biological constraints to reproduce coding properties of proprioceptive neurons in area 2 of primary somatosensory cortex. With this model, we demonstrate that the tendency for area 2 neurons in close physical proximity to share similar directional tuning can be explained by local topographic organisation driven by Mexican hat lateral effects, a phenomenon that is otherwise unobservable with the spatial resolution of available electrode microarray recordings. This provides, to the best of our knowledge, the first evidence of local topographic organisation in area 2 proprioceptive neurons. We also predict that the structure of proprioceptive receptive fields are typically multi-joint rather than single-joint in nature and provide, to the best of our knowledge, and find that our model best reproduces the tuning properties of neural data when training on natural kinematic recordings, rather than those from a stereotyped task, underlining the importance of training on data that reflect the natural distribution of sensory stimuli.
Cell Surface SARS-CoV-2 Nucleocapsid Protein Modulates Innate and Adaptive Immunity
Authors: López-Muñoz Alberto Domingo , Kosik Ivan , Holly Jaroslav , Yewdell Jonathan W.
Published: December 2021

SARS-CoV-2 nucleocapsid protein (N) induces strong antibody and T cell responses. Although considered to be localized in the cytosol, we readily detect N on the surface of live cells. N released by SARS-CoV-2 infected cells or N-expressing transfected cells binds to neighboring cells by electrostatic high-affinity binding to heparan sulfate and heparin, but not other sulfated glycosaminoglycans. N binds with high affinity to 11 human chemokines, including CXCL12β, whose chemotaxis of leukocytes is inhibited by N from SARS-CoV-2, SARS-CoV-1, and MERS CoV. Anti-N Abs bound to the surface of N expressing cells activate Fc receptor-expressing cells. Our findings indicate that cell surface N manipulates innate immunity by sequestering chemokines and can be targeted by Fc expressing innate immune cells. This, in combination with its conserved antigenicity among human CoVs, advances its candidacy for vaccines that induce cross-reactive B and T cell immunity to SARS-CoV-2 variants and other human CoVs, including novel zoonotic strains.
Elastin degradation markers are elevated in never-smokers with past history of prolonged exposure to secondhand tobacco smoke and are inversely associated with their lung function
Authors: Rakic Jelena Mustra , Zeng Siyang , Rohdin-Bibby Linnea , Van Blarigan Erin L , Liu Xingjian , Ma Shuren , Kane John P , Redberg Rita , Turino Gerard M. , Stock Eveline Oestreicher , Arjomandi Mehrdad
Published: December 2021

Background

Prolonged past exposure to secondhand tobacco smoke (SHS) in never-smokers is associated with occult obstructive lung disease and abnormal lung function, in particular reduced diffusing capacity. Previous studies have shown ongoing SHS exposure to be associated with increased elastin degradation markers (EDM) desmosine and isodesmosine.

Research Question

Are EDM levels elevated in persons with remote history of SHS exposure, and are those levels associated with reduced lung function?

Study Design and Methods

We measured the plasma levels of EDM from 193 never-smoking flight attendants with history of remote but prolonged SHS exposure in aircraft cabin and 103 nonsmoking flight attendants or sea-level control participants without history of cabin SHS exposure, and examined those levels versus their lung function with adjustment for covariates. The cabin SHS exposure was estimated based on airline employment history and dates of smoking ban enactment. EDM plasma levels were quantified by high-performance liquid chromatography and tandem mass spectrometry.

Results

The median [interquartile range; IQR] plasma EDM level for all participants was 0.30 [0.24 to 0.36] ng/mL with a total range of 0.16 to 0.65 ng/mL. Plasma EDM levels were elevated in those with history of exposure to cabin SHS compared to those not exposed (0.33±0.08 vs. 0.26±0.06 ng/mL; age- and sex-adjusted P<0.001). In those with history of cabin SHS-exposure, higher EDM levels were associated with lower diffusing capacity (parameter estimate (PE) [95%CI]=4.2 [0.4 to 8.0] %predicted decrease per 0.1 ng/mL increase in EDM; P=0.030). Furthermore, EDM levels were inversely associated with FEV1, FEV1/FVC, and FEF25-75 (PE [95%CI]=5.8 [2.1 to 9.4], 4.0 [2.2 to 5.7], and 12.5 [5.8 to 19.2]% predicted decrease per 0.1 ng/mL increase in EDM, respectively) (P<0.001).

Interpretation

Prolonged past exposure to SHS, even when remote, is associated with higher systemic elastin degradation markers that in turn is associated with lower lung function and in particular reduced diffusing capacity.
Buffering of transcription rate by mRNA half-life is a conserved feature of Rett syndrome models
Authors: Rodrigues Deivid C. , Mufteev Marat , Yuki Kyoko E. , Narula Ashrut , Wei Wei , Piekna Alina , Liu Jiajie , Pasceri Peter , Rissland Olivia S. , Wilson Michael D. , Ellis James
Published: December 2021

Models of MECP2 dysfunction in Rett syndrome (RTT) assume that transcription rate changes directly correlate with altered steady-state mRNA levels. However, limited evidence suggests that transcription rate changes are buffered by poorly understood compensatory post-transcriptional mechanisms. Here we measure transcription rate and mRNA half-life changes in RTT patient neurons using RATE-seq, and reinterpret nuclear and whole-cell RNAseq from Mecp2 mice. Genes are dysregulated by changing transcription rate only or half-life only and are buffered when both are changed. We utilized classifier models to understand the direction of transcription rate changes based on gene-body DNA sequence, and combined frequencies of three dinucleotides were better predictors than contributions by CA and CG. MicroRNA and RNA-Binding Protein (RBP) motifs were enriched in 3’UTRs of genes with half-life changes. Motifs for nuclear localized RBPs were enriched on buffered genes with increased transcription rate. Our findings identify post-transcriptional mechanisms in humans and mice that alter half-life only or buffer transcription rate changes when a transcriptional modulator gene is mutated in a neurodevelopmental disorder.
Idea paper: An envelope model of ecological disturbance
Authors: Friedman Nicholas R.
Published: December 2021

Disturbance is common in natural ecosystems, but increasingly defines them. While there are many descriptions for the dynamics of an ecosystem’s response to disturbance, there are few descriptions for the dynamics of the disturbance itself. I describe a novel application of a model based on the production of amplitude envelopes in acoustics and electronic music synthesis, with varying parameters Attack, Decay, Sustain, and Release (ADSR). I show that varying the parameters of the ADSR model is sufficient to produce and vary the qualitative disturbance regimes described by previous authors, and is capable of producing dynamics not previously considered. I tested the utility of the ADSR model by applying it to a logistic growth model. I found that manipulating the attack and release parameters of the ADSR model changes the population dynamics estimated by these models. This implies that responses to disturbance are determined not only by the resilience and resistance of the ecological system, but also the dynamics of the disturbance itself. My hope is that the ADSR model will prove useful to researchers in either describing disturbances in long-term ecological data, or in producing disturbances for simulations or experiments.
Acetyltransferases GCN5 and PCAF are required for B lymphocyte maturation in mice
Authors: Oksenych Valentyn , Su Dan , Daniel Jeremy A.
Published: December 2021

B lymphocyte development has two DNA recombination processes: V(D)J recombination of the immunoglobulin (Igh) gene variable region and class switching of theIghconstant regions from IgM to IgG, IgA, or IgE. V(D)J recombination is required for successful maturation of B cells from pro-B to pre-B to immature-B and then to mature B cells in the bone marrow. CSR occurs outside of the bone marrow when mature B cells migrate to peripheral lymphoid organs, such as spleen and lymph nodes. Both V(D)J recombination and CSR depend on an open chromatin state that makes DNA accessible to specific enzymes, recombination activating gene (RAG), and activation-induced cytidine deaminase (AID). Acetyltransferases GCN5 and PCAF possess redundant functions acetylating histone H3 lysine 9 (H3K9). Here, we generated a mouse model that lacks both GCN5 and PCAF in B cells. We found that double-deficient mice possess low levels of mature B cells in the bone marrow and peripheral organs, an accumulation of pro-B cells in bone marrow, and reduced CSR levels. We conclude that both GCN5 and PCAF are required for B cell developmentin vivo.
Transcriptional and Cytotoxic Responses of Human Intestinal Organoids to Interferon Types I, II, and III
Authors: Constant David A. , Van Winkle Jacob A. , VanderHoek Eden , Dekker Simone E. , Sofia M. Anthony , Regner Emilie , Modiano Nir , Tsikitis V. Liana , Nice Timothy J.
Published: December 2021

The three types of interferon (IFN) have roles in antimicrobial immunity and inflammation that must be properly balanced to maintain tissue homeostasis. For example, IFNs are elevated in the context of inflammatory bowel disease and may synergize with inflammatory cytokines such as tumor necrosis factor alpha (TNFα) to promote tissue damage. Prior studies suggest that in mouse intestinal epithelial cells (IECs), type III IFNs are preferentially produced during viral infections and are less cytotoxic than type I IFN. Here, we generated human IEC organoid lines from biopsies of ileum, ascending colon, and sigmoid colon of three healthy subjects to establish the baseline responses of normal human IECs to types I, II, and III IFN. We found that all IFN types elicited responses that were qualitatively consistent across intestinal biopsy sites. However, IFN types differed in magnitude of STAT1 phosphorylation and identity of genes in their downstream transcriptional programs. Specifically, there was a core transcriptional module shared by IFN types, but types I and II IFN stimulated unique transcriptional modules beyond this core gene signature. The transcriptional modules of type I and II IFN included pro-apoptotic genes, and expression of these genes correlated with potentiation of TNFα cytotoxicity. These data define the response profiles of healthy human IEC organoids across IFN types, and suggest that cytotoxic effects mediated by TNFα in inflamed tissues may be amplified by a simultaneous high-magnitude IFN response.
Translation rescue by targeting Ppp1r15a upstream open reading frame in vivo
Authors: Kidwell Ashley , Yadav Shiv Pratap Singh , Maier Bernhard , Zollman Amy , Ni Kevin , Halim Arvin , Janosevic Danielle , Myslinski Jered , Syed Farooq , Zeng Lifan , Waffo Alain Bopda , Banno Kimihiko , Xuei Xiaoling , Doud Emma H. , Dagher Pierre C. , Hato Takashi
Published: December 2021

The eIF2 initiation complex is central to maintaining a functional translation machinery. Extreme stress such as life-threatening sepsis exposes vulnerabilities in this tightly regulated system, resulting in an imbalance between the opposing actions of kinases and phosphatases on the main regulatory subunit eIF2α. Here, we report that translation shutdown is a hallmark of established sepsis-induced kidney injury brought about by excessive eIF2α phosphorylation and sustained by blunted expression of the counterregulatory phosphatase subunit Ppp1r15a. We determined that the blunted Ppp1r15a expression persists because of the presence of an upstream open reading frame (uORF). Overcoming this barrier with genetic approaches enabled the derepression of Ppp1r15a, salvaged translation and improved kidney function in an endotoxemia model. We also found that the loss of this uORF has broad effects on the composition and phosphorylation status of the immunopeptidome that extended beyond the eIF2α axis. Collectively, our findings define the breath and potency of the highly conserved Ppp1r15a uORF and provide a paradigm for the design of uORF-based translation rheostat strategies. The ability to accurately control the dynamics of translation during sepsis will open new paths for the development of therapies at codon level precision.