bluuebunny/crossref_metadata_2025 huggingface dataset:
Coral symbionts exhibit a polycistronic flavodiiron gene leading to functional proteins in photosynthesis
Authors: Shimakawa Ginga , Shoguchi Eiichi , Burlacot Adrien , Ifuku Kentaro , Che Yufen , Kumazawa Minoru , Tanaka Kenya , Nakanishi Shuji
Published: April 2021

Photosynthesis in cyanobacteria, green algae, and basal land plants is protected against excess reducing pressure on the photosynthetic chain by flavodiiron proteins (FLV) that dissipate photosynthetic electrons by reducing O2. In these organisms, the genes encoding FLV are always conserved in the form of a pair of two-type isozymes (FLVA and FLVB) that are believed to function in O2photo-reduction as a heterodimer. While coral symbionts (dinoflagellates of the family Symbiodiniaceae) are the only algae to harbor FLV in photosynthetic red plastid lineage, only one gene is found in transcriptomes and its role and activity remain unknown. Here, we characterized theFLVgenes in Symbiodiniaceae and found that its coding region is composed of tandemly repeated FLV sequences. By measuring the O2-dependent electron flow and P700 oxidation, we suggest that this atypical FLV is activein vivo. Based on the amino-acid sequence alignment and the phylogenetic analysis, we conclude that in coral symbionts, the gene pair for FLVA and FLVB have been fused to construct one coding region for a hybrid enzyme, which presumably occurred when or after both genes were inherited from basal green algae to the dinoflagellate. Immunodetection suggested the FLV polypeptide to be cleaved by a post-translational mechanism, adding it to the rare cases of polycistronic genes in eukaryotes. Our results demonstrate that FLV are active in coral symbionts with genomic arrangement that is unique to these species. The implication of these unique features on their symbiotic living environment is discussed.
Long-Term Persistence of Plasmids Targeted by CRISPR Interference in Bacterial Populations
Authors: Mamontov Viktor , Martynov Alexander , Morozova Natalia , Bukatin Anton , Staroverov Dmitry B. , Lukyanov Konstantin A. , Ispolatov Yaroslav , Semenova Ekaterina , Severinov Konstantin
Published: April 2021

CRISPR-Cas systems provide prokaryotes with an RNA-guided defense against foreign mobile genetic elements (MGEs) such as plasmids and viruses. A common mechanism by which MGEs avoid interference by CRISPR consists of acquisition of escape mutations in regions targeted by CRISPR. Here, using microbiological, live microscopy, and microfluidics analyses we demonstrated that plasmids can persist inEscherichia colicells at conditions of continuous targeting by the type I-E CRISPR-Cas system without acquiring any genetic alterations. We used mathematical modeling to show how plasmid persistence in a subpopulation of cells mounting CRISPR interference is achieved due to the stochastic nature of CRISPR interference and plasmid replication events. We hypothesize that the observed complex dynamics provides bacterial populations with long-term benefits due to the presence of mobile genetic elements in some cells, leading to diversification of phenotypes in the entire community and allowing rapid changes in the population structure to meet the demands of a changing environment.
Integrative physiological, biochemical and transcriptomic analysis of hexaploid wheat roots and shoots provides new insights into the molecular regulatory network during Fe & Zn starvation
Authors: Gupta Om Prakash , Pandey Vanita , Saini Ritu , Khandale Tushar , Singh Ajeet , Malik Vipin Kumar , Narwal Sneh , Ram Sewa , Singh Gyanendra Pratap
Published: April 2021

In plants, iron (Fe) & zinc (Zn) uptake and transportation from the rhizosphere to the grain is a critical process regulated by complex transcriptional regulatory networks. However, understanding the combined effect of Fe & Zn starvation on their uptake and transportation and the molecular regulatory networks that control them lack in wheat. Here, we performed a comprehensive physiological, biochemical and transcriptome analysis in two bread wheat genotypes,i.e.Narmada 195 and PBW 502, differing in inherent Fe & Zn content to understand the mechanism of Fe & Zn homeostasis. Compared to PBW 502, Narmada 195 exhibited increased tolerance to Fe & Zn withdrawal by an increased level of antioxidant enzymes and DPPH radical scavenging activity along with less malondialdehyde (MDA), H2O2level, increased PS accumulation and lower reduction of root and shoot Fe & Zn content and length, leaf chlorosis, and leaf area. By integrating physiological and biochemical data along with co-expression & functional genome annotation and gene expression analysis, we identified 25 core genes associated with four key pathways,i.e.Met cycle (10), PS biosynthesis (4), antioxidant (3) and transport system (8) that were significantly modulated by Fe & Zn withdrawal in both the genotypes. Genes of these four pathways were more considerably up-regulated in Narmada 195, allowing better tolerance to Fe & Zn withdrawal and efficient uptake and transportation of Fe & Zn. Chromosomal distribution and sub-genome wise mapping of these genes showed a contribution from all the chromosomes except group 5 chromosomes with the highest number of genes mapped to chromosome 4 (24%) and sub-genome D (40%). Besides, we also identified 26 miRNAs targeting 14 core genes across the four pathways. Together, our work provides a crucial angle for an in-depth understanding of regulatory cross-talk among physiological, biochemical and transcriptional reprogramming underlying Fe & Zn withdrawal in wheat. Core genes identified can serve as valuable resources for further functional research for genetic improvement of Fe & Zn content in wheat grain.

Highlight

Our work provides a crucial angle for a comprehensive understanding of the regulatory mechanism underlying Fe & Zn withdrawal associated with physiological, biochemical and transcriptional reprogramming in wheat.
Real-time lens-free visualization of strong light scattering by biogenic guanine platelets
Authors: Iwasaka Masakazu
Published: April 2021

Microscopic observation system without lens has a potential to realize ubiquitous sensing network detecting micro/nano biological hazards to modern society because the lens-free imaging device can provide an extremely compact microscope. In addition toin slicomicro-mirrors, liquid injectable organic micro-mirrors should be found and utilized for achieving the ideal imaging device for micro/nano objects. This study demonstrates a high contrast lens-free image of the projection from a biogenic guanine platelet floating in water. The fish guanine platelet generated intense and high directional diffraction as well as regular reflection of incident light. The light projection from guanine platelet individually formed an intense platelet-shaped image in real-time on CMOS image sensor arrays. A dynamic projection movie of the guanine platelet, the size of which was approximately 20 ∼ 40 μm × 5 ∼ 10 μm × 100 nm in thickness, was obtained in a small aqueous droplet whose height was less than 2 mm. The developed new lens-free technology using biogenic tiny platelet has an ability to portably visualize movements of the micro/nano objects interacting with the platelet. The compact lens-free inspection can contribute to keep our society in safe.
Cell layer-specific expression of the homeotic MADS-box transcription factor PhDEF contributes to modular petunia petal morphogenesis
Authors: Chopy M. , Cavallini-Speisser Q. , Chambrier P. , Morel P. , Just J. , Hugouvieux V. , Rodrigues Bento S. , Zubieta C. , Vandenbussche M. , Monniaux M.
Published: April 2021

Floral homeotic MADS-box transcription factors ensure the correct morphogenesis of floral organs, which are organized in different cell layers deriving from the meristematic L1, L2 and L3 layers. How cells from these distinct layers acquire their respective identity and coordinate their growth to ensure normal floral organ morphogenesis is unresolved. Here, we study petunia petals that form a limb and tube through congenital fusion, a complex morphology that coevolved with pollinators. We have identified petunia mutants expressing the B-class MADS-box genePhDEFin the epidermis or in the mesophyll of the petal only, called wico and star respectively. Strikingly, wico flowers form a strongly reduced tube while their limbs are almost normal, while star flowers form a normal tube but very reduced and unpigmented limbs, showing that petunia petal morphogenesis is highly modular. Comparative transcriptome analysis of star, wico and wild-type petals revealed a strong down-regulation of the anthocyanin production pathway in star petals including its major regulatorANTHOCYANIN2 (AN2).We found that PhDEF directly binds toAN2regulatory sequencein vitroby gel shift assay, andin vivoby chromatin immunoprecipitation, suggesting that PhDEF directly activates the petal pigmentation pathway by activatingAN2. Altogether, we show that cell-layer specific homeotic activity in petunia petals differently impacts tube and limb development, revealing the relative importance of the different cell layers in the modular architecture of petunia petals.
Comparison of the Drug Entrapment Efficiency of Almond Gum (Badam Pisin) to Span-60 Niosomes by Folin-Ciocalteu Assay
Authors: Hari Krishnan R
Published: April 2021

Almond gum (Badam Gum/ Badam Pisin) is a natural polymer composed of mainly carbohydrates (>90%) which makes it a potential candidate in targeted drug delivery. It contains 46% L-arabinose which is known to have fluid entrapment capacity. Various methods of drug targeting against tumor have been developed but due to poor solubility in body fluids, the bioavailability of the drug is reduced and so is its effectiveness. Almond gum is known to be water-soluble so the required bioavailability will be achieved and the drug dosage will also be minimal. Since it is of natural origin side effects will be less compared to that of artificially prepared drugs. Studies show that almond gum is known to have various health benefits including increasing immunity and acting as a coolant.Terminalia catappa(Indian almond), the source of almond gum is abundant in the Indian subcontinent hence making it more economical than chemical surfactants. The objective of this study is to determine whether Almond gum has a higher drug entrapment efficiency than that of Niosomes.
A global map of human pressures on tropical coral reefs
Authors: Andrello Marco , Darling Emily , Wenger Amelia , Suárez-Castro Andrés F. , Gelfand Sharla , Ahmadia Gabby N.
Published: April 2021

As human activities on the world’s oceans intensify, mapping human pressures is essential to develop appropriate conservation strategies and prioritize investments with limited resources. Here, we map non-climatic pressures on coral reefs using the latest quantitative data layers on fishing, nitrogen and sediment pollution, coastal and industrial development, and tourism. Across 54,596 coral reef pixels worldwide, we identify the top-ranked local pressure and estimate a cumulative pressure index mapped at 0.05-degree (∼5 km) resolution. Fishing was the most common top-ranked pressure followed by water pollution (nutrients and sediments), although there is substantial variation by regions. We also find that local pressures are similar inside and outside a proposed global portfolio of coral reef climate refugia. We provide the best available information to inform critical conservation strategies and ensure local pressures are effectively managed to increase the likelihood of the persistence of coral reefs to climate change.
Decisions in an Innate Behavioral Sequence
Authors: Cury Kevin M. , Axel Richard
Published: April 2021

Innate behaviors are comprised of ordered sequences of component actions that progress to satisfy drives. We have characterized the structure of egg-laying behavior inDrosophilain detail and observed that the sequence is not merely comprised of motor acts but also acts of sensory exploration that govern the transitions between component actions. We have identified a cluster of internal sensory neurons that provide information about the progression of the egg during ovipositor burrowing, a behavior necessary for the subterraneous deposition of the egg. These neurons impart sensory feedback that allows burrowing to continue to egg deposition or to abort in favor of further exploration. Diminished activity of these neurons upon completed egg expulsion may initiate the transition to the final phase of egg-laying, allowing the cycle to repeat. Sensory feedback therefore plays a critical role at decision points between transitions affording innate behaviors with an adaptive flexibility.
The global ocean size-spectrum from bacteria to whales
Authors: Hatton Ian A. , Heneghan Ryan F. , Bar-On Yinon M. , Galbraith Eric D.
Published: April 2021

It has long been hypothesized that aquatic biomass is evenly distributed among logarithmic body mass size-classes. Although this community structure has been observed locally among plankton groups, its generality has never been formally tested across all marine life, nor have its impacts by humans been broadly assessed. Here, we bring together data at the global scale to test the hypothesis from bacteria to whales. We find that biomass within most order of magnitude size-classes is indeed remarkably constant, near 1 Gt wet weight (1015grams), but that bacteria and whales are markedly above and below this value, respectively. Furthermore, human impacts have significantly truncated the upper one-third of the spectrum. Size-spectrum theory has yet to provide an explanation for what is possibly life’s largest scale regularity.

One Sentence Summary

Human activities have fundamentally altered one of life’s largest scale patterns; a global power law size distribution spanning bacteria to whales.
A daily-updated database and tools for comprehensive SARS-CoV-2 mutation-annotated trees
Authors: McBroome Jakob , Thornlow Bryan , Hinrichs Angie S. , De Maio Nicola , Goldman Nick , Haussler David , Corbett-Detig Russell , Turakhia Yatish
Published: April 2021

The vast scale of SARS-CoV-2 sequencing data has made it increasingly challenging to comprehensively analyze all available data using existing tools and file formats. To address this, we present a database of SARS-CoV-2 phylogenetic trees inferred with unrestricted public sequences, which we update daily to incorporate new sequences. Our database uses the recently-proposed mutation-annotated tree (MAT) format to efficiently encode the tree with branches labeled with parsimony-inferred mutations as well as Nextstrain clade and Pango lineage labels at clade roots. As of June 9, 2021, our SARS-CoV-2 MAT consists of 834,521 sequences and provides a comprehensive view of the virus’ evolutionary history using public data. We also present matUtils – a command-line utility for rapidly querying, interpreting and manipulating the MATs. Our daily-updated SARS-CoV-2 MAT database and matUtils software are available at http://hgdownload.soe.ucsc.edu/goldenPath/wuhCor1/UShER_SARS-CoV-2/ and https://github.com/yatisht/usher, respectively.
Integrative RNA-Seq analysis ofCapsicum annuum L.-Phytophthora capsici L.pathosystem reveals molecular cross-talk and activation of host defence response
Authors: Rabuma Tilahun , Gupta Om Prakash , Yadav Manju , Chhokar Vinod
Published: April 2021

Background

Chili pepper (Capsicum annuumL.) being one of an important member of the Solanaceae family, and its productivity is highly affected by the fungal pathogenPhytophthora capsiciL. Other to CM-344, the unavailability of resistant landraces to all possible strains ofP. capsiciimposes a serious threat to its global production. This is because of our current understanding of the molecular mechanisms associated with the defence response inC. annuum-P. capsicipathosystem is limited. Therefore, the current study used RNA-seq technology to dissect the genes associated with defence response againstP. capsiciinfection in two contrasting landraces,i.e.GojamMecha_9086 (Resistant) and Dabat_80045 (susceptible) exposed toP. capsiciinfection.

Results

The transcriptomes from 4 leaf samples (RC, RI, SC and SI) of chili pepper resulted in a total of 1,18, 879 assembled transcripts (with a mean TL of 813.23bp and N50 of 1,277bp) along with 52,384 pooled unigenes with (mean UL of 1029.36 bp and N50 of 1,403bp). The enrichment analysis of the transcripts indicated 23 different KEGG pathways under five main categories. Further, 774 and 484 differentially expressed genes (DEGs) were obtained from RC vs. RI and SC vs. SI leaf samples, respectively. Of these, 57 DEGs were found to be associated with defence responses againstP. capsiciinfection. The defence-related genes, such asLTPL, defensin J1-2-like, peroxidase 5-like, UGT, and GRP proteins-like, were more significantly upregulated in RC vs. RI. Furthermore, RT-qPCR analysis of six randomly selected genes validated the results of Illumina NextSeq500 sequencing results. Furthermore, a total of 58 TF families (bHLH most abundant) and 2,095 protein families (Protein kinase, PF00069, most abundant) were observed across all the samples with maximum hits in RI and SI samples.

Conclusions

RNA-Seq analysis of chili pepper’s duringP.capsiciinfection revealed differential regulation of genes associated with defence and signaling response with shared coordination of molecular function, cellular component and biological processing. The results presented here would enhance our present understanding of the defence response in chili pepper againstP. capsiciinfection, which could be utilized by the molecular breeders to develop resistant chili genotypes.
Deuterium Magnetic Resonance Spectroscopy of Early Treatment-Induced Changes in Tumour Lactatein vitro
Authors: Tan Josephine L , Djayakarsana Daniel , Wang Hanzhi , Chan Rachel W , Bailey Colleen , Lau Angus Z
Published: April 2021

Elevated production of lactate is a key characteristic of aberrant tumour cell metabolism and can be non-invasively measured as an early marker of tumour response using deuterium (2H) magnetic resonance spectroscopy (MRS). Following treatment, changes in the2H-labeled lactate signal could identify tumour cell death or impaired metabolic function, which precede morphological changes conventionally used to assess tumour response. In this work, the association between apoptotic cell death, extracellular lactate concentration, and early treatment-induced changes in the2H-labeled lactate signal was established in anin vitrotumour model. Experiments were conducted at 7 T on acute myeloid leukemia cells which had been treated with 10 µg/mL of the chemotherapeutic agent cisplatin. At 24 and 48 hours after cisplatin treatment, the cells were injected with 20 mM of [6,6’-2H2]glucose and scanned over two hours using a two-dimensional2H MR spectroscopic imaging sequence. The resulting signals from2H-labeled glucose, lactate, and water were quantified using a spectral fitting algorithm implemented on the OXford Spectroscopy Analysis (OXSA) MATLAB toolbox. After scanning, the cells were processed for histological stains (TUNEL [terminal deoxynucleotidyl transferase UTP nick end labeling] and H&E [hematoxylin and eosin]) to assess apoptotic area fraction and cell morphology respectively, while a colorimetric assay was used to measure extracellular lactate concentrations in the supernatant. Significantly lower levels of2H-labeled lactate were observed in the 48-hour treated cells compared to the untreated and 24-hour treated cells, and these changes were significantly correlated with an increase in apoptotic fraction and a decrease in extracellular lactate. By establishing the biological processes associated with treatment-induced changes in the2H-labeled lactate signal, these findings suggest that2H MRS of lactate may be valuable in evaluating early tumour response.
Differential Effects of endogenous and exogenous attention on sensory tuning
Authors: Fernández Antonio , Okun Sara , Carrasco Marisa
Published: April 2021

Covert spatial attention (without concurrent eye movements) improves performance in many visual tasks (e.g., orientation discrimination and visual search). However, both covert attention systems, endogenous (voluntary) and exogenous (involuntary), exhibit differential effects on performance in tasks mediated by spatial and temporal resolution suggesting an underlying mechanistic difference. We investigated whether these differences manifest in sensory tuning by assessing whether and how endogenous and exogenous attention differentially alter the representation of two basic visual dimensions: orientation and spatial frequency (SF). The same human observers detected a vertical grating embedded in noise in two separate experiments (with cues to elicit either endogenous or exogenous attention) and reverse correlation was used to infer the underlying neural representation from behavioral responses. Both endogenous and exogenous attention similarly improved performance at the attended location by enhancing the gain of all orientations without changing tuning width. In the SF dimension, endogenous attention enhanced the gain of SFs above and below the target SF, whereas exogenous attention only enhanced those above. Additionally, exogenous attention shifted peak sensitivity to SFs above the target SF, whereas endogenous attention did not. Both covert attention systems modulated sensory tuning via the same computation (gain changes). However, there were differences in the strength of the gain. Compared to endogenous attention, exogenous attention had a stronger orientation gain enhancement but a weaker overall SF gain enhancement. These differences in sensory tuning may underlie differential effects of endogenous and exogenous attention on performance.
The fluoride permeation pathway and anion recognition in Fluc family fluoride channels
Authors: McIlwain Benjamin C. , Gundepudi Roja , Koff B. Ben , Stockbridge Randy B.
Published: April 2021

Fluc family fluoride channels protect microbes against ambient environmental fluoride by undermining the cytoplasmic accumulation of this toxic halide. These proteins are structurally idiosyncratic, and thus the permeation pathway and mechanism have no analogy in other known ion channels. Although fluoride binding sites were identified in previous structural studies, it was not evident how these ions access aqueous solution, and the molecular determinants of anion recognition and selectivity have not been elucidated. Using x-ray crystallography, planar bilayer electrophysiology and liposome-based assays, we identify additional binding sites along the permeation pathway. We use this information to develop an oriented system for planar lipid bilayer electrophysiology and observe anion block at one of these sites, revealing insights into the mechanism of anion recognition. We propose a permeation mechanism involving alternating occupancy of anion binding sites that are fully assembled only as the substrate approaches.
Agronomic behavior of four cultivars and 56 F1 tomato populations
Authors: Choque Gonzalo Quispe
Published: April 2021

This research was conducted under a greenhouse at the National Vegetable Seed Production Center located in the municipality of Sipe Sipe, Quillacollo province with the aim of analyzing agronomic behavior in 56 F1 progenies and four hybrid tomato cultivars. The research consisted of 60 genotypes as treatments. Each experimental unit was made up of 6 plants. The variables evaluated were: number of flowers per inflorescence, number of fruits per cluster, weight of fruit, equatorial diameter, polar diameter, heart diameter, thickness of pericarp, number of fruits per plant, weight of fruit per plant, hardness and solids soluble . The data obtained were analyzed with descriptive statistics, correlation, cluster and principal component analysis. Significant correlations were found for the number of fruits per plant and number of flowers per inflorescence with the weight of fruit per plant. The polar dendogram identified four distant groups in the performance and quality components. The principal component analysis identified the degree of association between variables and genotypes, identifying groups correlated to components of fruit yield and quality.
From treadmill to trails: predicting performance of runners
Authors: Crowell B.
Published: April 2021

Previous laboratory studies have measured the energetic costs to humans of running at uphill and downhill slopes on a treadmill. This work investigates the extension of those results to the prediction of relative performance of athletes running on flat, hilly, or very mountainous outdoor courses. Publicly available race results in the Los Angeles area provided a set of 109,000 times, with 2200 runners participating in more than one race, so that their times could be compared under different conditions. I compare with the results of a traditional model in which the only parameters considered are total distance and elevation gain. Both the treadmill-based model and the gain-based model have some shortcomings, leading to the creation of a hybrid model that combines the best features of each.

Author summary

Running a race on a road allows absolute measures of performance. Trail running, however, has traditionally been thought of as a sport in which the only valid comparison is between different runners competing on the same course on the same day. Even the exact measurement of distance is considered to be unimportant, since courses and conditions vary so much.

An extreme example is the relatively new genre of “vertical” races, in which runners race up a mountain. In a typical example, the competitors cover a horizontal distance of 5 km, while climbing about 1000 m. The winner in one such race had a time almost triple that expected for a state-champion high school runner in a 5k road race. Clearly no comparison can be made here without taking into account the amount of climbing.

In noncompetitive contexts, many runners venture onto mountain trails, lightly dressed and with little equipment, so that it becomes important to be able to anticipate whether they will have the endurance needed to be able to safely complete a planned route. Again, this is impossible without some model of the effect of hill climbing.
Deacetylation of IFIT2 mediated by HDAC5 promotes the stemness and progression of glioma
Authors: Liu Ying , Zhang Kun , Peng Xingzhi , Zhou Zhuan , Zhou Peijun , Tang Siyuan , Li Dan , Shen Liangfang , Feng Deyun , Yang Lifang
Published: April 2021

Background

Glioma is the most common primary brain tumor, and the tumor stemness is a major regulatory factor affecting the progression, metastasis and recurrence of glioma. Recent research has shown that, nonhistone acetylation is widely involved in key cellular processes, including stemness regulation. The deacetylase inhibitors are promising new drugs, but their application and molecular mechanism in glioma have not been elucidated.

Methods

CCK8 and colony formation assay were used to detect cell proliferation, transwell assay was used to detect cell migration, flow cytometry was used to analyze cell apoptosis, sphere formation assay and western blot were used to detect the status of stemness. RNA-sequence, quantitative PCR and western blot were performed to screen the key molecules mediating LBH589 function. Immunoprecipitation (IP) and western blot were used to analyze the acetylation level of IFIT2. The SiRNA target HDAC4 or HDAC5, overexpression plasmids of acetyltransferases were used to identify the acetyltransferase and deacetylase regulating IFIT2. The regulatory mechanism was explored by IP and ubiquitination analysis. Finally, the xenograft tumor model in nude mice was constructed and further analyzed in vivo.

Results

The data showed that IFIT2 mediates the HDACi LBH589 inhibition on cell proliferation, migration and stemness, and contribution to autophagy and apoptosis in glioma. And the down-regulation of IFIT2 in glioma was confirmed to be related to its deacetylation by overexpression HDAC5, which promotes the stemness and progression of glioma. Further, deacetylation of IFIT2 by HDAC5 was demonstrated to induce its ubiquitination and subsequent protein instability, which led to loss of anti-tumor activity for IFIT2, and acceleration to glioma stemness and progression. In addition, the results indicated that IFIT2 inhibits PKC pathway, and suppressing of IFIT2 promotes tumor growth in vivo.

Conclusions

These results not only clarify a novel post-transcriptional regulatory mode of IFIT2, but also provide a new sight of molecular mechanism for HDACi in glioma.
Directional reorientation of migrating neutrophils is limited by suppression of receptor input signaling at the cell rear through myosin II activity
Authors: Hadjitheodorou Amalia , Bell George R. R. , Ellett Felix , Shastry Shashank , Irimia Daniel , Collins Sean R. , Theriot Julie A.
Published: April 2021

To migrate efficiently to target locations, cells must integrate receptor inputs while maintaining polarity: a distinct front that leads and a rear that follows. Here we investigate what is necessary to overwrite pre-existing front/rear polarity in neutrophil-like HL60 cells migrating inside straight microfluidic channels. Using subcellular optogenetic receptor activation, we show that receptor inputs can reorient weakly polarized cells, but the rear of strongly polarized cells is refractory to new inputs. Transient stimulation reveals a multi-step repolarization process, confirming that cell rear sensitivity to receptor input is the primary determinant of large-scale directional reversal. We demonstrate that the RhoA/ROCK/myosin II pathway limits the ability of receptor inputs to signal to Cdc42 and reorient migrating neutrophils. We discover that by tuning the phosphorylation of myosin regulatory light chain we can modulate the activity and localization of myosin II and thus the amenability of the cell rear to ‘listen’ to receptor inputs and respond to directional reprogramming.
Computational and Image Processing Methods for Analysis and Automation of Anatomical Alignment and Joint Spacing in Reconstructive Surgery
Authors: Chaudhary Usamah N. , Kelly Cambre N. , Wesorick Benjamin R. , Reese Cameron M. , Gall Ken , Adams Samuel B. , Sapiro Guillermo , Di Martino J. Matias
Published: April 2021

Purpose

Reconstructive surgeries to treat a number of musculoskeletal conditions, from arthritis to severe trauma, involve implant placement and reconstructive planning components. Anatomically matched 3D printed implants are becoming increasingly patient-specific; however the preoperative planning and design process requires several hours of manual effort from highly trained engineers and clinicians. Our work mitigates this problem by proposing algorithms for the automatic re-alignment of unhealthy anatomies, leading to more efficient, affordable, and scalable treatment solutions.

Methods

Our solution combines global alignment techniques such as iterative closest points (ICP) with novel joint space refinement algorithms. The latter is achieved by a low dimensional characterization of the joint space, computed from the distribution of the distance between adjacent points in a joint.

Results

Experimental validation is presented on real clinical data from human subjects. Compared with ground truth healthy anatomies, our algorithms can reduce misalignment errors by 22% in translation and 19% in rotation for the full foot-and-ankle and 37% in translation and 39% in rotation for the hind-foot only, achieving a performance comparable to expert technicians.

Conclusion

Our methods and histogram-based metric allow for automatic and unsupervised alignment of anatomies, a major step toward a fully automated and data driven re-positioning, designing, and diagnosing tool.
Analysis of variability of functionals of recombinant protein production trajectories based on limited data
Authors: Liao Shuting , Macharoen Kantharakorn , McDonald Karen A. , Nandi Somen , Paul Debashis
Published: April 2021

We propose a method for analyzing the variability in smooth, possibly nonlinear, functionals associated with a set of product production trajectories measured under different experimental conditions. The key challenge is to make meaningful inference on these parameters across different experimental conditions when only a limited number of measurements in time are collected for each treatment, and when there are only a few, or no, replicates available. For this purpose we adopt a modeling approach by representing the production trajectories in a B-spline basis, and develop a bootstrap-based inference procedure for the parameters of interest, also accounting for multiple comparisons. The methodology is applied to study two types of quantities of interest – “time to harvest” and “maximal productivity” in the context of an experiment on the production of certain recombinant proteins under laboratory conditions. We complement the findings by extensive numerical experiments that look into the effects of different types of bootstrap procedures and associated schemes for computingp-values for tests of hypotheses.
The response of desert biocrust bacterial communities to hydration-desiccation cycles
Authors: Baubin Capucine , Ran Noya , Siebner Hagar , Gillor Osnat
Published: April 2021

Rain events in arid environments are highly unpredictable, interspersing extended periods of drought. Therefore, following changes in desert soil bacterial communities during hydration-desiccation cycles in the field, was seldom attempted. Here, we assessed rain-mediated dynamics of active community in the Negev Desert biological soil crust (biocrust), and evaluated the changes in bacterial composition, potential function, and photosynthetic activity. We predicted that increased biocrust moisture would resuscitate the phototrophs, while desiccation would inhibit their activity. Our results show that hydration increased chlorophyll content, resuscitated the biocrustCyanobacteria,and induced potential phototrophic functions. However, decrease in the soil water content did not immediately decrease the phototrophs activity, though chlorophyll levels decreased. Moreover, while theCyanobacteriarelative abundance significantly increased,Actinobacteria, the former dominant taxa, significantly decreased in abundance. We propose that, following a rain event biocrust moisture significantly decreased, almost to drought levels, yet the response of the active bacterial community lagged, in contrast to topsoil. Possible explanations to the described rain-mediated bacteria dynamics are discussed.
Ozone Stress Responsive Gene Database (OSRGD ver. 1.1): a literature curated database for crop improvement
Authors: Prachi Yadav , Mina Usha
Published: April 2021

Ozone (O3) is a major abiotic stress which severely affects the growth and development of plants. In order to cope up with ozone stress, plants exhibit a plethora of morphological, physiological and molecular changes. Various molecular studies have been performed and a variety of genes exhibiting expression in response to ozone stress have been identified. However, no existing database has been designed yet to present information on ozone stress responsive genes differentially expressed across different plant species. The lack of a curated database limits the research potential in the area and therefore a cohesive database should be designed as a data repository of the ozone responsive genes. OSRGD ver. 1.1 is a user friendly web interface to explore ozone stress specific transcriptome dataset of different plant species. It allows users to retrieve the ozone stress responsive gene data by keyword based search. Each entry upon keyword query contains detailed information about the specific species, its foliar injury symptoms, pattern of gene expression, and platform used for gene expression analysis with reference literature. This comprehensive biocuration will offer researchers a better biological insight into plants’ response to ozone stress which will focus on development of climate smart crops through crop breeding.
Visual orientation discrimination skills are tightly linked with specific aspects of human intelligence
Authors: Mikellidou Kyriaki , Lambrou Nefeli , Georgiou Ellada , Avraamides Marios
Published: April 2021

We investigate the notion that basic visual information is acting as a building block for more complex cognitive processes in humans. Specifically, we measured individual visual orientation discrimination thresholds to report significant correlations against the total standardised intelligence quotient (IQ), verbal-IQ and non-verbal IQ scores evaluated using the Wechsler Abbreviated Scale of Intelligence Second Edition (WASI-II) test battery comprising Verbal Reasoning, Block Design, Similarities and Matrix Reasoning subtests (N=92). A multiple linear regression analysis showed that participants’ performance in our visual discrimination task, could be explained only by individual scores in Verbal Reasoning which quantifies the ability to comprehend and describe words and Matrix Reasoning, which evaluates general visual processing skills including abstract and spatial perception. Our results demonstrate that low-level visual abilities and high-level cognitive processes are more tightly interwoven together than previously thought and this result could pave the way for further research on how cognition can be defined by basic sensory processes.
An extended admixture pulse model reveals the limitations to Human-Neandertal introgression dating
Authors: Iasi Leonardo N. M. , Ringbauer Harald , Peter Benjamin M.
Published: April 2021

Neandertal DNA makes up 2-3% of the genomes of all non-African individuals. The patterns of Neandertal ancestry in modern humans have been used to estimate that this is the result of gene flow that occurred during the expansion of modern humans into Eurasia, but the precise dates of this event remain largely unknown. Here, we introduce an extended admixture pulse model that allows joint estimation of the timing and duration of gene flow. This model leads to simple expressions for both the admixture segment distribution and the decay curve of ancestry linkage disequilibrium, and we show that these two statistics are closely related. In simulations, we find that estimates of the mean time of admixture are largely robust to details in gene flow models, but that the duration of the gene flow can only be recovered if gene flow is very recent and the exact recombination map is known. These results imply that gene flow from Neandertals into modern humans could have happened over hundreds of generations. Ancient genomes from the time around the admixture event are thus likely required to resolve the question when, where, and for how long humans and Neandertals interacted.
Genetic diversity in facultatively sexual populations and its implications for the origins of self-incompatibility in algae and fungi
Authors: Smith A.S.A. , Penington S. , Letter I. , Wilson D.B. , Constable G.W.A.
Published: April 2021

The evolutionary mechanism that drove the establishment of self-incompatibility in early sexual eukaryotes is still a debated topic. While a number of competing hypotheses have been proposed, many have not received detailed theoretical attention. In particular, the hypothesis that self-incompatibility increases the benefits of genetic recombination in sexual haploids has been comparatively understudied. In this paper we address this topic by mathematically deriving how the probability of mating with a genetically distinct individual changes as a function of the presence or absence of self-incompatible mating type classes. We find that although populations with mating types successfully engage in sexual reproduction less frequently than their self-compatible competitors, they can nevertheless engage in useful sex with genetically distinct partnersmorefrequently. This conclusion holds when the number of sexual reproductive events per generation is low (i.e. in small populations with low rates of facultative sexual reproduction). Finally we demonstrate the potential for frequency-dependent selection in competitive dynamics between self-compatible and self-incompatible types. These analytic results provide a baseline for studying the sex advantage enhancer model for the evolutionary origin of mating types within each specific hypothesis for the evolution of recombination.

PACS

87.23.-n Ecology and evolution, 87.23.Kg Dynamics of evolution, 02.50.Ey Stochastic processes

2000 MSC

37N25: Dynamical systems in biology, 60J70: Applications of diffusion theory (population genetics, absorption problems, etc.)
Heterogeneous non-canonical nucleosomes predominate in yeast cellsin situ
Authors: Tan Zhi Yang , Cai Shujun , Noble Alex J. , Chen Jon K. , Shi Jian , Gan Lu
Published: April 2021

Nuclear processes depend on the organization of chromatin, whose basic units are cylinder-shaped complexes called nucleosomes. A subset of mammalian nucleosomesin situ(inside cells) resembles the canonical structure determinedin vitro25 years ago. Nucleosome structurein situis otherwise poorly understood. Using cryo-ET and 3-D classification analysis of budding yeast cells, here we find that canonical nucleosomes account for less than 10% of total nucleosomes expectedin situ. In a strain in which H2A-GFP is the sole source of histone H2A, class averages that resemble canonical nucleosomes both with and without GFP densities are foundex vivo(in nuclear lysates), but notin situ. These data suggest that the budding yeast intranuclear environment favors multiple non-canonical nucleosome conformations. Using the structural observations here and the results of previous genomics and biochemical studies, we propose a model in which the average budding yeast nucleosome’s DNA is partially detachedin situ.
ANP32A represses Wnt signaling across tissues tissues thereby protecting against joint and heart disease
Authors: Monteagudo Silvia , Cornelis Frederique M. F. , Wang Xiangdong , de Roover Astrid , Peeters Tine , Quintiens Jolien , Sermon An , de Almeida Rodrigo C. , Meulenbelt Ingrid , Lories Rik J.
Published: April 2021

Wnt signaling is key to diverse homeostatic and pathological processes. This cascade is hyper-activated in osteoarthritis, the most common joint disease. Yet, fundamental aspects of Wnt signaling remain undiscovered. Here, we report that ANP32A negatively regulates Wnt signaling across tissues. In cartilage, loss ofAnp32atriggered Wnt hyper-activation. Mechanistically, ANP32A directly interacted with Wnt pathway components and inhibited Wnt target genes via histone acetylation masking. Wnt antagonist treatment reduced severity of osteoarthritis inAnp32a-deficient mice preventing osteophyte formation, contrasting with cartilage-protective effects of ANP32A on oxidative stress. Hence, dual therapy targeting Wnt signaling and oxidative stress inAnp32a-deficient mice ameliorated more osteoarthritis features than individual treatments.Anp32aloss also resulted in Wnt hyper-activation in the heart with cardiac hypertrophy, and in the hippocampus, shedding light on mechanisms for reported links between ANP32A and Alzheimer’s disease. Collectively, this work reveals that ANP32A is a translationally relevant repressor of Wnt signaling, impacting homeostasis and disease across tissues.
A translation control module coordinates germline stem cell differentiation with ribosome biogenesis duringDrosophilaoogenesis
Authors: Martin Elliot T. , Blatt Patrick , Ngyuen Elaine , Lahr Roni , Selvam Sangeetha , Yoon Hyun Ah M. , Pocchiari Tyler , Emtenani Shamsi , Siekhaus Daria E. , Berman Andrea , Fuchs Gabriele , Rangan Prashanth
Published: April 2021

Ribosomal defects perturb stem cell differentiation, causing diseases called ribosomopathies. How ribosome levels control stem cell differentiation is not fully known. Here, we discovered three RNA helicases are required for ribosome biogenesis and forDrosophilaoogenesis. Loss of these helicases, which we named Aramis, Athos and Porthos, lead to aberrant stabilization of p53, cell cycle arrest and stalled GSC differentiation. Unexpectedly, Aramis is required for efficient translation of a cohort of mRNAs containing a 5’-Terminal-Oligo-Pyrimidine (TOP)-motif, including mRNAs that encode ribosomal proteins and a conserved p53 inhibitor,NovelNucleolar protein 1 (Non1). The TOP-motif co-regulates the translation of growth-related mRNAs in mammals. As in mammals, the La-related protein co-regulates the translation of TOP-motif containing RNAs duringDrosophilaoogenesis. Thus, a previously unappreciated TOP-motif inDrosophilaresponds to reduced ribosome biogenesis to co-regulate the translation of ribosomal proteins and a p53 repressor, thus coupling ribosome biogenesis to GSC differentiation.
Hybridization and the Coexistence of Species
Authors: Irwin Darren , Schluter Dolph
Published: April 2021

It is thought that two species can coexist if they use different resources present in the environment, yet this assumes that species are completely reproductively isolated. We model coexistence outcomes for two sympatric species that are ecologically differentiated but have incomplete reproductive isolation. The consequences of interbreeding depend crucially on hybrid fitness. When hybrid fitness is high, just a small rate of hybridization can lead to collapse of two species into one. Low hybrid fitness can cause population declines, making extinction of one or both species likely. High intrinsic growth rates result in higher reproductive rates when populations are below carrying capacity, reducing the probability of extinction and increasing the probability of stable coexistence at moderate levels of assortative mating and hybrid fitness. Very strong but incomplete assortative mating can induce low hybrid fitness via a mating disadvantage to rare genotypes, and this can stabilize coexistence of two species at high but incomplete levels of assortative mating. Given these results and evidence that it may take many millions of years of divergence before related species become sympatric, we postulate that coexistence of closely-related species is more often limited by insufficient assortative mating than by insufficient ecological differentiation.
A Tensegrity-Graph Optimization Framework for Estimating Intracellular Stiffness
Authors: Bhattacharya Raktim
Published: April 2021

In this paper we present a formulation for estimating intracellular stiffness using tensegrity principles. We demonstrate that the new tensegrity model, based on random graphs over dense nodes, can predict well known mechanical characteristics of epithelial and mesenchymal cells.
Sterilizing Effects of Novel Regimens Containing TB47, Clofazimine and Linezolid in a Murine Model of Tuberculosis
Authors: Yu Wei , Buhari Yusuf , Wang Shuai , Tian Xirong , Hameed H. M. Adnan , Lu Zhili , Chiwala Gift , Alam Md Shah , Cook Gregory M. , Maslov Dmitry A. , Zhong Nanshan , Zhang Tianyu
Published: April 2021

Toxicity and inconvenience associated with the use of injectable drug-containing regimens for tuberculosis (TB) have made all-oral regimens a preferred alternative. Widespread resistance to fluoroquinolones and pyrazinamide makes it essential to identify new drug candidates and study their effects on current regimens for TB. TB47 is a pyrazolo[1,5-a]pyridine-3-carboxamide with powerful synergisticin vitroandin vivoactivities against mycobacteria, especially with clofazimine. Here, we investigated the bactericidal and sterilizing activities of novel oral regimens containing TB47 + clofazimine + linezolid, and the potential roles of levofloxacin and/or pyrazinamide in such drug combinations. Using a well-established mouse model, we assessed the effect of these regimens on bacterial burden in the lung during treatment and relapse (4 months after stopping treatment + immunosuppression). Our findings indicate that the TB47 + clofazimine + linezolid + pyrazinamide, with/without levofloxacin, regimens had fast-acting (4 months) sterilizing activity and no relapse was observed. When pyrazinamide was excluded from the regimen, treatment times were longer (5-6 months) to achieve sterilizing conditions. We propose that TB47 + clofazimine + linezolid can form a highly sterilizing block for use as an alternative pan-TB regimen.