bluuebunny/crossref_metadata_2025 huggingface dataset:
Light-dependent phosphorylation of THRUMIN1 regulates its association with actin filaments and 14-3-3 proteins
Authors: Dwyer Matthew E , Hangarter Roger P
Published: August 2021

Light-dependent chloroplast movements in leaf cells contribute to the optimization of photosynthesis. Low-light conditions induce chloroplast accumulation along periclinal cell surfaces, providing greater access to available light, whereas high light induces movement of chloroplasts to anticlinal cell surfaces, providing photodamage protection and allowing more light to reach underlying cell layers. The THRUMIN1 protein is required for normal chloroplast movements in Arabidopsis (Arabidopsis thaliana) and has been shown to localize at the plasma membrane and to undergo rapid light-dependent interactions with actin filaments through the N-terminal intrinsically disordered region (IDR). A predicted WASP-Homology 2 domain was found in the IDR but mutations in this domain did not disrupt localization of THRUMIN1:YFP to actin filaments. A series of other protein truncations and site-directed mutations of known and putative phosphorylation sites indicated that a phosphomimetic mutation (serine to aspartic acid) at position 170 disrupted localization of THRUMIN1 to actin filaments. However, the phosphomimetic mutant rescued the thrumin1-2 mutant phenotype for chloroplast movement and raises questions about the role of THRUMIN1’s interaction with actin. Mutation of serine 146 to aspartic acid also resulted in cytoplasmic localization of THRUMIN1:YFP in Nicotiana benthamiana. Mutations to a group of putative zinc-binding cysteine clusters implicate the C-terminus of THRUMIN1 in chloroplast movement. Phosphorylation-dependent association of THRUMIN1 with 14-3-3 KAPPA and OMEGA were also identified. Together, these studies provide insights into the mechanistic role of THRUMIN1 in light-dependent chloroplast movements.
COMPARISON OF RADIATION DOSE AND IMAGE QUALITY IN HEAD CT SCANS AMONG MULTIDETECTOR CT SCANNERS
Authors: Abuzaid Mohamed M , Elshami Wiam , Tekin H O , Sulieman Abdelmoneim , Bradley D A
Published: August 2021

The present study compares three different multidetector CT (MDCT) scanners for routine brain imaging in terms of image quality and radiation doses. The volume CT dose index (CTDIvol), dose-length product (DLP), and effective dose (E) were calculated. Subjective image assessment was obtained based on a scale ranging from 1 (unacceptable) to 5 (optimum). All images scored 3.5 or over, with the 160-slice MDCT images being favoured. For the 4-, 16- and 160-slice MDCT scanners, the respective median values for CTDIvol were 57 mGy, 41 mGy, and 28 mGy; DLP values were 901 mGy.cm, 680 mGy.cm, and 551 mGy.cm; and effective doses were 2 mSv, 1.5 mSv, and 1 mSv, respectively. Compared to the 160-slice MDCT, the dose values for the 4- and 16-slice units were significantly greater. In practice, the CT modality used must be carefully selected to avoid elevated radiation doses and maintain image quality.
Researchers’ institutional mobility: bibliometric evidence on academic inbreeding and internationalization
Authors: Macháček Vít , Srholec Martin , Ferreira Márcia R , Robinson-Garcia Nicolas , Costas Rodrigo
Published: August 2021

We propose institutional mobility indicators based on researchers’ mobility flows in 22 major fields of science across 1,130 Leiden Ranking institutions from 64 countries. We base our indicators on data from the Dimensions database and Global Research Identifier Database. We use researchers’ first and last affiliations to estimate the extent authors have moved across institutions as well as countries. For each institution, we quantify the shares of researchers with the same affiliation (insiders), those who came from another institution within the country (domestic outsiders), and those coming from a different country (foreign outsiders). Institutions in Central, Eastern, and Southern Europe have the highest share of insiders, whereas institutions in Northern America and Western and Northern Europe have a higher share of foreign outsiders. Foreign outsiders are most common in small and wealthy countries. No disciplinary differences are observed, as captured by the field classification scheme of Dimensions.
High-yield ‘one-pot’ biosynthesis of raspberry ketone, a high-value fine chemical
Authors: Moore Simon J , Tosi Tommaso , Bell David , Hleba Yonek B , Polizzi Karen M , Freemont Paul S
Published: August 2021

Cell-free extract and purified enzyme-based systems provide an attractive solution to study biosynthetic strategies towards a range of chemicals. 4-(4-hydroxyphenyl)-butan-2-one, also known as raspberry ketone, is the major fragrance component of raspberry fruit and is used as a natural additive in the food and sports industry. Current industrial processing of the natural form of raspberry ketone involves chemical extraction from a yield of ∼1–4 mg kg−1 of fruit. Due to toxicity, microbial production provides only low yields of up to 5–100 mg L−1. Herein, we report an efficient cell-free strategy to probe into a synthetic enzyme pathway that converts either L-tyrosine or the precursor, 4-(4-hydroxyphenyl)-buten-2-one, into raspberry ketone at up to 100% conversion. As part of this strategy, it is essential to recycle inexpensive cofactors. Specifically, the final enzyme step in the pathway is catalyzed by raspberry ketone/zingerone synthase (RZS1), an NADPH-dependent double bond reductase. To relax cofactor specificity towards NADH, the preferred cofactor for cell-free biosynthesis, we identify a variant (G191D) with strong activity with NADH. We implement the RZS1 G191D variant within a ‘one-pot’ cell-free reaction to produce raspberry ketone at high-yield (61 mg L−1), which provides an alternative route to traditional microbial production. In conclusion, our cell-free strategy complements the growing interest in engineering synthetic enzyme cascades towards industrially relevant value-added chemicals.
Occurrence of Mummy Berry Associated with Huckleberry (Vaccinium membranaceum) Caused by Monilinia spp. in Oregon
Authors: Hagerty Christina , Gardner Sarah , Kroese Duncan R. , Yin Chuntao , Paulitz Timothy Carl , Pscheidt Jay W.
Published: August 2021

In this Short Communication we describe the occurrence of mummy berry associated with huckleberry (Vaccinium membranaceum) caused by Monilinia spp. in Oregon. To our knowledge, this is the first report of a Monilinia spp. associated with mummy berry of huckleberry in Oregon. Sequence data from our specimens reveal the closest identity was Monilinia vaccinii-corymbosi, a pathogen of commercial blueberry (Vaccinium corymbosum). This may be a new species of Monilinia, not previously reported on huckleberry, and further investigation is needed. Of specific importance, the huckleberry holds cultural importance as a sacred First Food of the Confederated Tribes of the Umatilla Indian Reservation and other Pacific Northwest tribes. Although plant pathogen management in natural landscapes presents unique challenges, we will work with tribal authorities to determine whether cultural management techniques may mitigate yield loss due to Monilinia spp.
Genetic Diversity and Population Structure of the Rice False Smut Pathogen Ustilaginoidea virens in the Sichuan–Chongqing Region
Authors: Fang Anfei , Fu Zhuangyuan , Wang Zexiong , Fu Yuhang , Qin Yubao , Bai Zhenxu , Tan Ze , Cai Junsong , Yang Yuheng , Yu Yang , Sun Wenxian , Bi Chaowei
Published: August 2021

Rice false smut caused by Ustilaginoidea virens is one of the most devastating fungal diseases of rice panicles worldwide. In this study, two novel molecular markers derived from single nucleotide polymorphism-rich genomic DNA fragments and a previously reported molecular marker were used for analyzing the genetic diversity and population structure of 167 U. virens isolates collected from nine areas in the Sichuan–Chongqing region, China. A total of 62 haplotypes were identified, and a few haplotypes with high frequency were found and distributed in two to three areas, suggesting gene flow among different geographical populations. All isolates were divided into six genetic groups. Groups I and VI were the largest, with 61 and 48 isolates, respectively. The pairwise FST values showed significant genetic differentiation among all compared geographical populations. Analysis of molecular variance showed that intergroup genetic variation accounted for 40.17% of the total genetic variation, while 59.83% of genetic variation came from intragroup genetic variation. The unweighted pair-group method with arithmetic means dendrogram and population structure revealed that the genetic composition of isolates collected from Santai, Nanchong, Yongchuan, and Wansheng dominated by the same genetic subgroup was different from those collected from other areas. In addition, genetic recombination was found in a few isolates. These findings will help to improve the strategies for rice false smut management and resistance breeding, such as evaluating breeding lines with different isolates or haplotypes at different elevations and landforms.
Pairing automated mark–recapture and social network models to explore the effects of landscape configuration on hummingbird foraging patterns
Authors: Gannon D. G. , Hadley A. S. , Frey S. J. K.
Published: August 2021

Landscape changes can alter pollinator movement and foraging patterns which can in turn influence the demographic processes of plant populations. We leveraged social network models and four fixed arrays of five hummingbird feeders equipped with radio frequency identification (RFID) data loggers to study rufous hummingbird (
Selasphorus rufus
) foraging patterns in a heterogeneous landscape. Using a space-for-time approach, we asked whether forest encroachment on alpine meadows could restrict hummingbird foraging movements and impede resource discovery. We fit social network models to data on 2221 movements between feeders made by 29 hummingbirds. Movements were made primarily by females, likely due to male territoriality and early migration dates. Distance was the driving factor in determining the rate of movements among feeders. The posterior mean effects of forest landscape variables (local canopy cover and intervening forest cover) were negative, but with considerable uncertainty. Finally, we found strong reciprocity in hummingbird movements, indicative of frequent out and back movements between resources. Together, these findings suggest that reciprocal movements by female hummingbirds could help maintain bidirectional gene flow among nearby subpopulations of ornithophilous plants; however, if the distance among meadows increases with further forest encroachment, this may limit foraging among progressively isolated meadows.
Avian blood parasite richness decreases with major histocompatibility complex class I loci number
Authors: Vincze Orsolya , Loiseau Claire , Giraudeau Mathieu
Published: August 2021

Major histocompatibility complex (MHC) genes are among the most polymorphic in the vertebrate genome. The high allele diversity is believed to be maintained primarily by sexual and pathogen-mediated balancing selection. The number of MHC loci also varies greatly across vertebrates, most notably across birds. MHC proteins play key roles in presenting antigens on the cell surface for recognition by T cells, with class I proteins specifically targeting intracellular pathogens. Here, we explore the hypothesis that MHC class I diversity (measured as loci number) coevolves with haemosporidian parasite burden of the host. Using data on 54 bird species, we demonstrate that high-MHC class I diversity is associated with significantly lower richness of
Plasmodium
,
Haemoproteus
as well as overall haemosporidian parasite lineages, the former thus indicating more efficient protection against intracellular pathogens. Nonetheless, the latter associations were only detected when MHC diversity was assessed using cloning and not 454 pyrosequencing-based studies, nor across all genotyping methods combined. Our results indicate that high-MHC class I diversity might play a key role in providing qualitative resistance against diverse haemosporidian parasites in birds, but further clarification is needed for the origin of contrasting results when using different genotyping methods for MHC loci quantification.
Family-specific chemical profiles provide potential kin recognition cues in the sexually cannibalistic spider
Argiope bruennichi
Authors: Weiss Katharina , Schneider Jutta M.
Published: August 2021

Kin recognition, the ability to detect relatives, is important for cooperation, altruism and also inbreeding avoidance. A large body of research on kin recognition mechanisms exists for vertebrates and insects, while little is known for other arthropod taxa. In spiders, nepotism has been reported in social and solitary species. However, there are very few examples of kin discrimination in a mating context, one coming from the orb-weaver
Argiope bruennichi
. Owing to effective mating plugs and high rates of sexual cannibalism, both sexes of
A. bruennichi
are limited to a maximum of two copulations. Males surviving their first copulation can either re-mate with the current female (monopolizing paternity) or leave and search for another. Mating experiments have shown that males readily mate with sisters but are more likely to leave after one short copulation as compared with unrelated females, allowing them to search for another mate. Here, we ask whether the observed behaviour is based on chemical cues. We detected family-specific cuticular profiles that qualify as kin recognition cues. Moreover, correlations in the relative amounts of some of the detected substances between sexes within families indicate that kin recognition is likely based on subsets of cuticular substances, rather than entire profiles.
Fitness cost from fluctuating ultraviolet radiation inDaphnia magna
Authors: Stábile Franca , Brönmark Christer , Hansson Lars-Anders , Lee Marcus
Published: August 2021

Solar ultraviolet radiation (UVR) is an important environmental threat for organisms in aquatic systems, but its temporally variable nature makes the understanding of its effects ambiguous. The aim of our study was to assess potential fitness costs associated with fluctuating UVR in the aquatic zooplankterDaphnia magna. We investigated individual survival, reproduction and behaviour when exposed to different UVR treatments. Individuals exposed to fluctuating UVR, resembling natural variations in cloud cover, had the lowest fitness (measured as the number of offspring produced during their lifespan). By contrast, individuals exposed to the same, but constant UVR dose had similar fitness to control individuals (not exposed to UVR), but they showed a significant reduction in daily movement. The re-occurring threat response to the fluctuating UVR treatment thus had strong fitness costs forD. magna, and we found no evidence for plastic behavioural responses when continually being exposed to UVR, despite the regular, predictable exposure schedule. In a broader context, our results imply that depending on how variable a stressor is in nature, populations may respond with alternative strategies, a framework that could promote rapid population differentiation and local adaptation.
Triple contagion: a two-fears epidemic model
Authors: Epstein Joshua M. , Hatna Erez , Crodelle Jennifer
Published: August 2021

We present a differential equations model in which contagious disease transmission is affected by contagious fear of the disease and contagious fear of the control, in this case vaccine. The three contagions are coupled. The two fears evolve and interact in ways that shape distancing behaviour, vaccine uptake, and their relaxation. These behavioural dynamics in turn can amplify or suppress disease transmission, which feeds back to affect behaviour. The model reveals several coupled contagion mechanisms for multiple epidemic waves. Methodologically, the paper advances infectious disease modelling by including human behavioural adaptation, drawing on the neuroscience of fear learning, extinction and transmission.
Enhanced photothermal absorption in iridescent feathers
Authors: Rogalla Svana , Patil Anvay , Dhinojwala Ali , Shawkey Matthew D. , D'Alba Liliana
Published: August 2021

The diverse colours of bird feathers are produced by both pigments and nanostructures, and can have substantial thermal consequences. This is because reflectance, transmittance and absorption of differently coloured tissues affect the heat loads acquired from solar radiation. Using reflectance measurements and heating experiments on sunbird museum specimens, we tested the hypothesis that colour and their colour producing mechanisms affect feather surface heating and the heat transferred to skin level. As predicted, we found that surface temperatures were strongly correlated with plumage reflectivity when exposed to a radiative heat source and, likewise, temperatures reached at skin level decreased with increasing reflectivity. Indeed, nanostructured melanin-based iridescent feathers (green, purple, blue) reflected less light and heated more than unstructured melanin-based colours (grey, brown, black), as well as olives, carotenoid-based colours (yellow, orange, red) and non-pigmented whites. We used optical and heat modelling to test if differences in nanostructuring of melanin, or the bulk melanin content itself, better explains the differences between melanin-based feathers. These models showed that the greater melanin content and, to a lesser extent, the shape of the melanosomes explain the greater photothermal absorption in iridescent feathers. Our results suggest that iridescence can increase heat loads, and potentially alter birds' thermal balance.
A multi-layer model for the early detection of COVID-19
Authors: Shmueli Erez , Mansuri Ronen , Porcilan Matan , Amir Tamar , Yosha Lior , Yechezkel Matan , Patalon Tal , Handelman-Gotlib Sharon , Gazit Sivan , Yamin Dan
Published: August 2021

Current COVID-19 screening efforts mainly rely on reported symptoms and the potential exposure to infected individuals. Here, we developed a machine-learning model for COVID-19 detection that uses four layers of information: (i) sociodemographic characteristics of the individual, (ii) spatio-temporal patterns of the disease, (iii) medical condition and general health consumption of the individual and (iv) information reported by the individual during the testing episode. We evaluated our model on 140 682 members of Maccabi Health Services who were tested for COVID-19 at least once between February and October 2020. These individuals underwent, in total, 264 516 COVID-19 PCR tests, out of which 16 512 were positive. Our multi-layer model obtained an area under the curve (AUC) of 81.6% when evaluated over all the individuals in the dataset, and an AUC of 72.8% when only individuals who did not report any symptom were included. Furthermore, considering only information collected before the testing episode—i.e. before the individual had the chance to report on any symptom—our model could reach a considerably high AUC of 79.5%. Our ability to predict early on the outcomes of COVID-19 tests is pivotal for breaking transmission chains, and can be used for a more efficient testing policy.
TSPO: an emerging role in appetite for a therapeutically promising biomarker
Authors: Wang Joshua , Beecher Kate
Published: August 2021

There is accumulating evidence that an obesogenic Western diet causes neuroinflammatory damage to the brain, which then promotes further appetitive behaviour. Neuroinflammation has been extensively studied by analysing the translocator protein of 18 kDa (TSPO), a protein that is upregulated in the inflamed brain following a damaging stimulus. As a result, there is a rich supply of TSPO-specific agonists, antagonists and positron emission tomography ligands. One TSPO ligand, etifoxine, is also currently used clinically for the treatment of anxiety with a minimal side-effect profile. Despite the neuroinflammatory pathogenesis of diet-induced obesity, and the translational potential of targeting TSPO, there is sparse literature characterizing the effect of TSPO on appetite. Therefore, in this review, the influence of TSPO on appetite is discussed. Three putative mechanisms for TSPO's appetite-modulatory effect are then characterized: the TSPO–allopregnanolone–GABA
A
R signalling axis, glucosensing in tanycytes and association with the synaptic protein RIM-BP1. We highlight that, in addition to its plethora of functions, TSPO is a regulator of appetite. This review ultimately suggests that the appetite-modulating function of TSPO should be further explored due to its potential therapeutic promise.
Ultrasensitivity and bistability in covalent-modification cycles with positive autoregulation
Authors: Jeynes-Smith Cailan , Araujo Robyn P.
Published: August 2021

Switch-like behaviours in biochemical networks are of fundamental significance in biological signal processing, and exist as two distinct types: ultra-sensitivity and bistability. Here we propose two new models of a reversible covalent-modification cycle with positive autoregulation (PAR), a motif structure that is thought to be capable of both ultrasensitivity and bistability in different parameter regimes. These new models appeal to a modelling framework that we call
complex-complete
, which accounts fully for the molecular complexities of the underlying signalling mechanisms. Each of the two new models encodes a specific molecular mechanism for PAR. We demonstrate that the modelling simplifications for PAR models that have been used in previous work, which rely on Michaelian approximations, are unable to accurately recapitulate the qualitative signalling responses supported by our detailed models. Strikingly, we show that complex-complete PAR models are capable of new qualitative responses such as one-way switches and a ‘prozone’ effect, depending on the specific PAR-encoding mechanism, which are not supported by Michaelian simplifications. Our results highlight the critical importance of accurately representing the molecular details of biochemical signalling mechanisms, and strongly suggest that the Michaelian approximation is inadequate for predictive models of enzyme-mediated chemical reactions with added regulations such as PAR.
Dengue virus 3 genotype I shows natural changes in heparan sulphate binding sites, cell interactions, and neurovirulence in a mouse model
Authors: Andrade Adriana S. , Ferreira Rafaela S. , Guedes Maria Isabel M. C. , Dias Jamile , Pinheiro Mariana A. , Arias Nidia Esther C. , Reis Erik V. S. , de Souza Fernanda G. , Kroon Erna G.
Published: August 2021

Dengue virus (DENV) is the most prevalent pathogen of the Flaviviridae family. Due to the considerable increase in DENV incidence and spread, symptoms such as CNS involvement have increased. Heparan sulphate (HS) was the first molecule identified as an adhesion factor for DENV in mammalian cells. Viral phenotypes with different HS interactions are associated with various clinical symptoms, including neurological alterations. Here, using in silico analyses, in vitro studies, and the in vivo mouse model, we characterized two natural circulating DENV3 genotype I (GI) lineage 1 (L1) in Brazil–DENV3 MG-20 (from Minas Gerais) and DENV3 PV_BR (from Rondônia) that present divergent neurovirulent profiles and sensitivity to sulphated molecules. We identified substitutions at the viral envelope (E) in positions 62 and 123 as likely responsible for the differences in neurovirulence. The E62K and E123Q substitutions in DENV3 MG-20 and DENV3 PV_BR, respectively, greatly influenced in silico electrostatic density and heparin docking results. In vivo, mice inoculated with DENV3 MG-20 died, but not those infected with DENV3 PV_BR. The clinical symptoms, such as paralysis of the lower limbs and meningoencephalitis, and histopathology, also differed between the inoculated groups. In vitro heparin and heparinases assays further demonstrated the biological impact of these substitutions. Other characteristics that have been previously associated with alterations in cell tropism and neurovirulence, such as changes in the size of lysis plaques and differences in cytopathic effects in glioblastoma cells, were also observed.
High parental vaccine motivation at a neighborhood-based vaccine and testing site serving a predominantly Latinx community
Authors: Naso Jamie , Rojas Susy , Peng James , Marquez Carina , Contreras Maria , Castellanos Edgar , Rojas Susana , Rubio Luis , Jones Diane , Jacobo Jon , Black Douglas , Tulier-Laiwa Valerie , Martinez Jacqueline , Chamie Gabriel , Pilarowski Genay , DeRisi Joseph , Havlir Diane , Petersen Maya
Published: August 2021

Purpose

To understand vaccine attitudes of Latinx parents highly impacted by COVID-19. Methods. In April 2021, we surveyed parents about their attitudes for COVID-19 vaccination of their children at a community-based outdoor testing/vaccination site serving predominantly low-income, Latinx persons in San Francisco.

Results

Among 1,033 parents (75% Latinx), 92% would “definitely” or “probably” vaccinate their children. Vaccine hesitancy was higher for younger children; concerns included side effects and impacts on fertility. Doctors and community organizations were noted as trusted sources of information, including among vaccine-hesitant parents.

Conclusion

Latinx parents accessing neighborhood-based COVID-19 testing/vaccination services are highly motivated to vaccinate their children for COVID-19.
Vibrio cholerae multifaceted adaptive strategies in response to bacteriophage predation in an endemic region of the Democratic Republic of the Congo
Authors: Alam Meer T. , Mavian Carla , Salemi Marco , Tagliamonte Massimiliano S. , Paisie Taylor , Cash Melanie N. , Angermeyer Angus , Seed Kimberley D. , Camilli Andrew , Maisha Felicien Masanga , Senga R. Kabangwa Kakongo , Morris J. Glenn , Ali Afsar
Published: August 2021

Bacteriophage predation of toxigenic Vibrio cholerae O1 (the causative agent of cholera) has been linked with seasonal patterns of disease and with clinical response to infection in humans 1-4. However, we still lack a clear demonstration of how the interplay between bacteria and bacteriophage can influence shifts in strain populations. We analyzed toxigenic V. cholerae O1 isolated from patients in the Great Lakes, a cholera endemic region of the Democratic Republic of the Congo (DRC), between 2013-2017. Bayesian phylogeography shows that all strains derived from the East Africa T10 introduction event5, consistent with establishment of a regional endemic focus, and identified two major lineages, with the most recent correlating to ST515, a cholera cluster previously found in the Lake Kivu and expanding northward6. We also identified a novel ICP1 bacteriophage, genetically distinct from previous ICP1 isolates detected in Asia 7,8, from stool samples of cholera patients. The presence of phages in specific regions of the DRC resulted in the independent emergence, along both internal and external branches of the cholera phylogeny, of distinct mutational pathways in genes of the O1 biosynthetic gene cluster associated with phage resistance. Our data evidence, for the first time, V. cholerae multi-peaked adaptive landscape during outbreaks, and a complex co-evolutionary dynamic linked to presence of predatory phages.
Analysis of Preplatelets and Their Barbell Platelet Derivatives by Imaging Flow Cytometry
Authors: Kemble Sam , Dalby Amanda , Lowe Gillian C , Nicolson Phillip LR , Watson Steve P , Senis Yotis , Thomas Steven G. , Harrison Paul
Published: August 2021

Circulating large “preplatelets” undergo fission via barbell platelet intermediates into two smaller, mature platelets. In this study, we determine whether preplatelets and/or barbells are equivalent to reticulated/immature platelets by using ImageStream flow cytometry (ISFC) and super-resolution microscopy. Immature platelets, preplatelets and barbells were quantified in healthy and thrombocytopenic mice, healthy human volunteers, and patients with immune thrombocytopenia (ITP) or undergoing chemotherapy. Preplatelets and barbells were 1.9%+0.18/1.7%+0.48 (n=6) and 3.3%+1.6/0.5%+0.27 (n=12) of total platelet counts in murine and human whole blood, respectively. Both preplatelets and barbells exhibited high expression of HLA-I with high thiazole orange and mitotracker fluorescence. Tracking dye experiments confirmed that preplatelets transform into barbells and undergo fissionex vivoto increase platelet counts, with dependence upon the cytoskeleton and normal mitochondrial respiration. Samples from antibody-induced thrombocytopenia in mice and patients with ITP had increased levels of both preplatelets and barbells correlating with immature platelet levels. Furthermore, barbells were absent post-chemotherapy in patients. In mice,in vivobiotinylation confirmed that barbells, but not all large platelets, were immature. This study demonstrates that a subpopulation of large platelets are immature preplatelets that can transform into barbells and undergo fission during maturation.
AlphaMap: An open-source Python package for the visual annotation of proteomics data with sequence specific knowledge
Authors: Voytik Eugenia , Bludau Isabell , Willems Sander , Hansen Fynn , Brunner Andreas-David , Strauss Maximilian T. , Mann Matthias
Published: August 2021

Integrating experimental information across proteomic datasets with the wealth of publicly available sequence annotations is a crucial part in many proteomic studies that currently lacks an automated analysis platform. Here we present AlphaMap, a Python package that facilitates the visual exploration of peptide-level proteomics data. Identified peptides and post-translational modifications in proteomic datasets are mapped to their corresponding protein sequence and visualized together with prior knowledge from UniProt and with expected proteolytic cleavage sites. The functionality of AlphaMap can be accessed via an intuitive graphical user interface or – more flexibly – as a Python package that allows its integration into common analysis workflows for data visualization. AlphaMap produces publication-quality illustrations and can easily be customized to address a given research question.

Availability and implementation

AlphaMap is implemented in Python and released under an Apache license. The source code and one-click installers are freely available at https://github.com/MannLabs/alphamap.

Supplementary information

A detailed user guide for AlphaMap is provided as supplementary data.
OPT3 Transports Copper to the Phloem, Mediates Shoot-to-Root Copper Signaling and Crosstalk Between Copper and Iron Homeostasis inA. thaliana
Authors: Chia Ju-Chen , Yan Jiapei , Ishka Maryam Rahmati , Faulkner Marta Marie , Simons Eli , Huang Rong , Smieska Louisa , Woll Arthur , Tappero Ryan , Kiss Andrew , Jiao Chen , Fei Zhangjun , Kochian Leon V. , Walker Elsbeth , Piñeros Miguel , Vatamaniuk Olena K.
Published: August 2021

Copper and iron are essential micronutrients but are toxic when accumulating in cells in excess. Thus, their uptake by roots is tightly regulated. While plants sense and respond to local copper availability, the systemic regulation of copper uptake has not been documented. By contrast, both local and systemic control for iron uptake has been reported. Iron abundance in the phloem has been suggested to act systemically, regulating the expression of iron uptake genes in the root. Consistently, shoot-to-root iron signaling is disrupted inA. thalianamutants lacking the phloem companion cell-localized iron transporter, AtOPT3:opt3mutants overaccumulate iron in leaves while constitutively upregulating iron deficiency-responsive genes in roots. We report that AtOPT3 transports copper and mediates its delivery from source leaves to sinks including young leaves and developing embryos. Consequently, theopt3mutant accumulates less copper in the phloem, is sensitive to copper deficiency, and mounts transcriptional copper deficiency response in roots. Copper rescues these defects. Notably, feeding theopt3mutant with copper or ironviathe phloem in leaves downregulates the expression of both copper and iron-deficiency marker genes in roots, suggesting that copper and iron can substitute each other’s function in the phloem in shoot-to-root communication.

One-sentence summary

AtOPT3 loads copper and iron into the phloem companion cells, for subsequent distribution to sink tissues and systemic signaling of copper and iron deficiency.
Novel compound inhibitors of HIV-1NL4-3 Vpu
Authors: Robinson Carolyn A. , Lyddon Terri D. , Gil Hwi Min , Evans David T. , Kuzmichev Yury V. , Richard Jonathan , Finzi Andrés , Welbourn Sarah , Rasmussen Lynn , Miranda Nebane N. , Gupta Vandana V. , Ananthan Sam , Cai Zhaohui , Wonderlich Elizabeth R. , Augelli-Szafran Corinne E. , Bostwick Robert , Ptak Roger G. , Schader Susan M. , Johnson Marc C.
Published: August 2021

HIV-1 Vpu targets the host cell proteins CD4 and BST-2/Tetherin for degradation, ultimately resulting in enhanced virus spread and host immune evasion. The discovery and characterization of small molecules that antagonize Vpu would further elucidate the contribution of Vpu to pathogenesis and lay the foundation for the study of a new class of novel HIV-1 therapeutics. To identify novel compounds that block Vpu activity, we developed a cell-based ‘gain of function’ assay that produces a positive signal in response to Vpu inhibition. To develop this assay, we took advantage of the viral glycoprotein, GaLV Env. In the presence of Vpu, GaLV Env is not incorporated into viral particles, resulting in non-infectious virions. Vpu inhibition restores infectious particle production. Using this assay, a high throughput screen of >650,000 compounds was performed to identify inhibitors that block the biological activity of Vpu. From this screen, we identified several positive hits but focused on two compounds from one structural family, SRI-41897 and SRI-42371. It was conceivable that the compounds inhibited the formation of infectious virions by targeting host cell proteins instead of Vpu directly, so we developed independent counter-screens for off target interactions of the compounds and found no off target interactions. Additionally, these compounds block Vpu-mediated modulation of CD4, BST-2/Tetherin and antibody dependent cell-mediated toxicity (ADCC). Unfortunately, both SRI-41897 and SRI-42371 were shown to be specific to the N-terminal region of NL4-3 Vpu and did not function against other, more clinically relevant, strains of Vpu.
WGA-LP: a pipeline for Whole Genome Assembly of contaminated reads
Authors: Rossi N. , Colautti A. , Iacumin L. , Piazza C.
Published: August 2021

Abstract

Whole Genome Assembly (WGA) of bacterial genomes with short reads is a quite common task as DNA sequencing has become cheaper with the advances of its technology. The process of assembling a genome has no absolute golden standard (Del Angel et al. (2018)) and it requires to perform a sequence of steps each of which can involve combinations of many different tools. However, the quality of the final assembly is always strongly related to the quality of the input data. With this in mind we built WGA-LP, a package that connects state-of-art programs and novel scripts to check and improve the quality of both samples and resulting assemblies.

WGA-LP, with its conservative decontamination approach, has shown to be capable of creating high quality assemblies even in the case of contaminated reads.

Availability and Implementation

WGA-LP is available on GitHub (https://github.com/redsnic/WGA-LP) and Docker Hub (https://hub.docker.com/r/redsnic/wgalp). The web app for node visualization is hosted by shinyapps.io (https://redsnic.shinyapps.io/ContigCoverageVisualizer/).

Contact

Nicolò Rossi, olocin.issor@gmail.com

Supplementary information

Supplementary data are available at bioRxiv online.
Photorealistic reconstruction of visual texture from EEG signals
Authors: Wakita Suguru , Orima Taiki , Motoyoshi Isamu
Published: August 2021

Recent advances in brain decoding have made it possible to classify image categories based on neural activity. Increasing numbers of studies have further attempted to reconstruct the image itself. However, because images of objects and scenes inherently involve spatial layout information, the reconstruction usually requires retinotopically organized neural data with high spatial resolution, such as fMRI signals. In contrast, spatial layout does not matter in the perception of ‘texture’, which is known to be represented as spatially global image statistics in the visual cortex. This property of ‘texture’ enables us to reconstruct the perceived image from EEG signals, which have a low spatial resolution. Here, we propose an MVAE-based approach for reconstructing texture images from visual evoked potentials measured from observers viewing natural textures such as the textures of various surfaces and object ensembles. This approach allowed us to reconstruct images that perceptually resemble the original textures with a photographic appearance. A subsequent analysis of the dynamic development of the internal texture representation in the VGG network showed that the reproductivity of texture rapidly improves at 200 ms latency in the lower layers but improves more gradually in the higher layers. The present approach can be used as a method for decoding the highly detailed ‘impression’ of sensory stimuli from brain activity.
Investigating the Contribution of White Matter Hyperintensities and Cortical Thickness to Empathy in Neurodegenerative and Cerebrovascular Diseases
Authors: Ozzoude Miracle , Varriano Brenda , Beaton Derek , Ramirez Joel , Holmes Melissa F. , Scott Christopher J.M. , Gao Fuqiang , Sunderland Kelly M. , McLaughlin Paula , Rabin Jennifer , Goubran Maged , Kwan Donna , Roberts Angela , Bartha Robert , Symons Sean , Tan Brian , Swartz Richard H. , Abrahao Agessandro , Saposnik Gustavo , Masellis Mario , Lang Anthony E. , Marras Connie , Zinman Lorne , Shoesmith Christen , Borrie Michael , Fischer Corinne E. , Frank Andrew , Freedman Morris , Montero-Odasso Manuel , Kumar Sanjeev , Pasternak Stephen , Strother Stephen C. , Pollock Bruce G. , Rajji Tarek K. , Seitz Dallas , Tang-Wai David F. , Chum Marvin , Turnbull John , Dowlatshahi Dar , Hassan Ayman , Casaubon Leanne , Mandzia Jennifer , Sahlas Demetrios , Breen David P. , Grimes David , Jog Mandar , Steeves Thomas D.L. , Arnott Stephen R. , Black Sandra E. , Finger Elizabeth , Tartaglia Maria Carmela
Published: August 2021

Introduction: Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases.

Methods: 513 participants with Alzheimer’s Disease/Mild Cognitive Impairment, Amyotrophic Lateral Sclerosis, Frontotemporal Dementia (FTD), Parkinson’s Disease, or Cerebrovascular Disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness.

Results: A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex(female), global cognition, and right parietal and occipital WMH.

Conclusions: Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.
Genome-wide DNA methylation and multi-omics study of human chondrocyte ontogeny and an epigenetic clock analysis of adult chondrocytes
Authors: Sarkar Arijita , Lee Siyoung , Shkhyan Ruzanna , Liu Nancy Q. , Handel Ben Van , Magallanes Jenny , Lee Youngjoo , Tao Litao , Segil Neil , Ernst Jason , Horvath Steve , Evseenko Denis
Published: August 2021

Articular chondrocytes undergo functional changes and their regenerative potential declines with age. Although the molecular mechanisms guiding articular cartilage aging is poorly understood, DNA methylation is known to play a mechanistic role in aging. However, our understanding of DNA methylation in chondrocyte development across human ontogeny is limited. To better understand DNA methylome changes, methylation profiling was performed in human chondrocytes. This study reveals association between methylation of specific CpG sites and chondrocyte age. We also determined the putative binding targets of STAT3, a key age-patterned transcription factor in fetal chondrocytes and genetic ablation of STAT3 induced a global genomic hypermethylation. Moreover, an epigenetic clock built for adult human chondrocytes revealed that exposure of aged adult human chondrocytes to STAT3 agonist, decreased epigenetic age. Taken together, this work will serve as a foundation to understand development and aging of chondrocytes with a new perspective for development of rejuvenation agents for synovial joints.
Computational analysis of B cell receptor repertoires in COVID-19 patients using deep embedded representations of protein sequences
Authors: Kim Inyoung , Byun Sang Yoon , Kim Sangyeup , Choi Sangyoon , Noh Jinsung , Chung Junho , Kim Byung Gee
Published: August 2021

Analyzing B cell receptor (BCR) repertoires is immensely useful in evaluating one’s immunological status. Conventionally, repertoire analysis methods have focused on comprehensive assessments of clonal compositions, including V(D)J segment usage, nucleotide insertions/deletions, and amino acid distributions. Here, we introduce a novel computational approach that applies deep-learning-based protein embedding techniques to analyze BCR repertoires. By selecting the most frequently occurring BCR sequences in a given repertoire and computing the sum of the vector representations of these sequences, we represent an entire repertoire as a 100-dimensional vector and eventually as a single data point in vector space. We demonstrate that this new approach enables us to not only accurately cluster BCR repertoires of coronavirus disease 2019 (COVID-19) patients and healthy subjects but also efficiently track minute changes in immune status over time as patients undergo treatment. Furthermore, using the distributed representations, we successfully trained an XGBoost classification model that achieved a mean accuracy rate of over 87% given a repertoire of CDR3 sequences.
Functional characterization of two variants in the mitochondrial topoisomerase gene TOP1MT that impact regulation of the mitochondrial genome
Authors: Khatib Iman Al , Deng Jingti , Symes Andrew , Kerr Marina , Zhang Hongliang , Huang Sharyin , Pommier Yves , Khan Aneal , Shutt Timothy E
Published: August 2021

TOP1MT encodes a mitochondrial topoisomerase that is important for mtDNA regulation, and that is involved in mitochondrial replication, transcription and translation. Two variants predicted to affect TOP1MT function (V1 - R198C and V2 - V338L) were identified by exome sequencing of a newborn with hypertrophic cardiomyopathy. As no pathogenic TOP1MT variants had been confirmed previously, we characterized these variants for their ability to rescue several TOP1MT functions in knockout cells. Consistent with these TOP1MT variants contributing to the patient phenotype, comprehensive characterization suggests that both variants had impaired activity. Critically, neither variant was able to restore steady state levels of mitochondrial-encoded proteins, nor reduced oxidative phosphorylation when re-expressed in TOP1MT knockout cells. However, the two variants behaved differently in some respects. While the V1 variant was better at restoring transcript levels, the V2 variant was able to restore mtDNA copy number and replication. These findings suggest that the different TOP1MT variants affect distinct TOP1MT functions. Altogether, these findings begin to provide insight into the many roles that TOP1MT plays in the maintenance and expression of the mitochondrial genome, and how impairments in this important protein may lead to human pathology.
Genomic remnants of ancestral hydrogen and methane metabolism in Archaea drive anaerobic carbon cycling
Authors: Adam Panagiotis S. , Kolyfetis George E. , Bornemann Till L.V. , Vorgias Constantinos E. , Probst Alexander J.
Published: August 2021

Methane metabolism is among the hallmarks of Archaea, originating very early in their evolution. Other than its two main complexes, methyl-CoM reductase (Mcr) and tetrahydromethanopterin-CoM methyltransferase (Mtr), there exist other genes called “methanogenesis markers” that are believed to participate in methane metabolism. Many of them are Domains of Unknown Function. Here we show that these markers emerged together with methanogenesis. Even if Mcr is lost, the markers and Mtr can persist resulting in intermediate metabolic states related to the Wood-Ljungdahl pathway. Beyond the markers, the methanogenic ancestor was hydrogenotrophic, employing the anaplerotic hydrogenases Eha and Ehb. The selective pressures acting on Eha, Ehb, and Mtr partially depend on their subunits’ membrane association. Integrating the evolution of all these components, we propose that the ancestor of all methane metabolizers was an autotrophic H2/CO2 methanogen that could perhaps use methanol but not oxidize alkanes. Hydrogen-dependent methylotrophic methanogenesis has since emerged multiple times independently, both alongside a vertically inherited Mcr or from a patchwork of ancient transfers. Through their methanogenesis genomic remnants, Thorarchaeota and two newly reconstructed order-level lineages in Archaeoglobi and Bathyarchaeota act as metabolically versatile players in carbon cycling of anoxic environments across the globe.
Gene-dependent yeast cell death pathway requires AP-3 vesicle trafficking leading to vacuole membrane permeabilization
Authors: Stolp Zachary D. , Kulkarni Madhura , Liu Yining , Zhu Chengzhang , Jalisi Alizay , Lin Si , Casadevall Arturo , Cunningham Kyle W. , Pineda Fernando J. , Teng Xinchen , Hardwick J. Marie
Published: August 2021

Unicellular eukaryotes are suggested to undergo self-inflicted destruction. However, molecular details are sparse by comparison to the mechanisms of cell death known for human cells and animal models. Here we report a molecular pathway inSaccharomyces cerevisiaeleading to vacuole/lysosome membrane permeabilization and cell death. Following exposure to heat-ramp conditions, a model of environmental stress, we observed that yeast cell death occurs over several hours, suggesting an ongoing molecular dying process. A genome-wide screen for death-promoting factors identified all subunits of the AP-3 adaptor complex. AP-3 promotes stress-induced cell death through its Arf1-GTPase-dependent vesicle trafficking function, which is required to transport and install proteins on the vacuole/lysosome membrane, including a death-promoting protein kinase Yck3. Time-lapse microscopy revealed a sequence of events where AP-3-dependent vacuole permeability occurs hours before the loss of plasma membrane integrity. An AP-3-dependent cell death pathway appears to be conserved in the human pathogenCryptococcus neoformans.