bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in wheat rhizosphere microbiota in response to chemical inputs, plant genotype and phenotypic plasticity
Authors: Jacquiod Samuel , Raynaud Tiffany , Pimet Eric , Ducourtieux Chantal , Casieri Leonardo , Wipf Daniel , Blouin Manuel
Published: May 2021

Since modern wheat varieties are grown with chemical inputs, we ignore if changes observed in rhizosphere microorganisms between ancient and modern varieties are due to i) breeding-induced changes in plant genotype, ii) modifications of the environment via synthetic chemical inputs, or (iii) phenotypic plasticity, defined as the interaction between the genotype and the environment. In the field, we evaluated the effects of various wheat varieties (modern and ancient) grown with or without chemical inputs (N-fertilizer, fungicide and herbicide together) in a crossed factorial design. We analysed rhizosphere bacteria and fungi by amplicons sequencing and mycorrhizal association by microscopic observations. When considered independently of plant genotype, chemical inputs were responsible for an increase in dominance for bacteria and decrease in evenness for bacteria and fungi. Independently of inputs, modern varieties had richer and more even bacterial communities compared to ancient varieties. Phenotypic plasticity had a significant effect: bacterial and fungal diversity decreased when inputs were applied in ancient varieties but not in modern ones. Mycorrhiza were more abundant in modern than ancient varieties, and less abundant when using chemical inputs. Although neglected, phenotypic plasticity is important to understand the evolution of plant-microbiota associations and a relevant target in breeding programs.
Long-term stress and trait anxiety alter brain network balance in dynamic decisions during working memory
Authors: Liu Liangying , Wu Jianhui , Geng Haiyang , Liu Chao , Luo Yuejia , Luo Jing , Qin Shaozheng
Published: May 2021

Long-term stress has a profound impact on the human brain and cognition, and trait anxiety influences stress-induced adaptive and maladaptive effects. However, the neurocognitive mechanisms underlying long-term stress and trait anxiety interactions remain elusive. Here we investigated how long-term stress and trait anxiety interact to affect dynamic decisions during working-memory (WM) by altering functional brain network balance. In comparison to controls, male participants under long-term stress experienced higher psychological distress and exhibited faster evidence accumulation but had a lower decision-threshold during WM. This corresponded with hyper-activation in the anterior insula, less WM-related deactivation in the default-mode network, and stronger default-mode network decoupling with the frontoparietal network. Critically, high trait anxiety under long-term stress led to slower evidence accumulation through higher WM-related frontoparietal activity, and increased decoupling between the default-mode and frontoparietal networks. Our findings provide neurocognitive evidence for long-term stress and trait anxiety interactions on executive functions with (mal)adaptive changes.
Effects ofPlatycodon grandiflorumon Gut Microbiota and Immune System of Immunosuppressed Mouse
Authors: Jhang So Yun , Lee Sung-Hyen , Lee Eun-Byeol , Choi Ji-Hye , Bang Sohyun , Jeong Misun , Jang Hwan-Hee , Kim Hyun-Ju , Lee Hae-Jeung , Jeong Hyun Cheol , Lee Sung Jin
Published: May 2021

Platycodon grandiflorum(PG) has been used as a traditional remedy to control immune related diseases. However, there is limited information about its immune stimulating effects on the immunosuppressed model. The main bioactive components such as saponins are known to con-tribute to controlling immune activity. Thus, we developed an aged red PG (PGS) with 2.6 times of platycodin D, one of the saponins. We treated PG and PGS (PG-diets) to immunosuppressed mice via cyclophosphamide (CPA) injection. After 2weeks of the supplement, 16S rRNA sequencing was performed to investigate the effects of PG-diets on the gut microbiota and immune system in the immune suppressed model. PG-diets groups showed an increased abundance of microorganism in immune-deficient mice compared to the control NC group, indicating PG-diets have a distinct effect on microbial communities. Detection of specific genera related to the immune related biomarkers in PG-diets groups can support their effects on the immune system. Especially, theAkkermansiashowed a significant decrease of abundance in response to the CPA treatment in the NC group at the genus level, but its abundance increased in response to the PG-diets treatment in the PG-diets groups. We also found that the modulation of gut microbiome by PG-diets was correlated with body weight as one of important immune biomarkers, though not much difference was found between PG and PGS effects. The results demonstrate that PG-diets may improve the health benefits of immune suppressed mice by altering the gut microbiome.
Reversion of antibiotic resistance in drug-resistant bacteria using non-steroidal anti-inflammatory drug benzydamine
Authors: Liu Yuan , Tong Ziwen , Shi Jingru , Deng Tian , Li Ruichao , Xiao Xia , Wang Zhiqiang
Published: May 2021

Antimicrobial resistance has been a growing concern that gradually undermines our tradition treatment regimen. The fact that few antibacterial drugs with new scaffolds or targets have been approved in the past two decades aggravates this crisis. Repurposing previously approved drugs as potent antibiotic adjuvants offers a cost-effective strategy to mitigate the development of resistance and tackle the increasing infections by multidrug-resistant (MDR) bacteria. Herein, we found that benzydamine, a widely used non-steroidal anti-inflammatory drug in clinic, remarkably potentiated broad-spectrum antibiotic-tetracyclines activity against a panel of clinical important resistant pathogens, including MRSA, VRE, MCRPEC andtet(X)-positive Gram-negative bacteria. Further mechanistically experiments showed that benzydamine dissipated membrane potential (ΔΨ) in both Gram-positive and negative bacteria, which in turn upregulated the transmembrane proton gradient (ΔpH) and promoted the uptake of tetracyclines. Additionally, benzydamine exacerbated the oxidative stress by triggering the production of ROS and suppressing GAD system-mediated oxidative defensive. This mode of action explains the great bactericidal activity of the doxycycline-benzydamine combination against different metabolic states of bacteria including persister cells. As a proof-of-concept, thein vivoefficacy of this combination therapy was evidenced in multiple animal infection models. These findings revealed that benzydamine is a promising tetracycline antibiotics adjuvant and has the potential to address life-threatening infections by MDR bacteria.
Hepatitis B virus polymerase restricts LINE-1 retrotransposition
Authors: Ariumi Yasuo
Published: May 2021

Long interspersed element-1 (LINE-1, L1) retrotransposon composes about 17% of the human genome. However, genetic and biochemical interactions between L1 and hepatitis B virus (HBV) remain poorly understood. In this study, we found that HBV restricts L1 mobility without inhibiting the L1 promoter activity. Notably, HBV polymerase (Pol) strongly inhibited L1 retrotransposition in a reverse transcriptase (RT)-independent manner. Indeed, the ribonuclease H (RNase H) domain was essential for inhibition of L1 retrotransposition. L1 ORF1p RNA-binding protein predominantly localized into cytoplasmic RNA granule termed P-body. However, HBV Pol sequestered L1 ORF1p from P-body and colocalized with L1 ORF1p in cytoplasm, when both proteins were co-expressed. Altogether, HBV Pol seems to restrict L1 mobility through a sequestration of L1 ORF1p from P-body. Thus, these results suggest a novel function or activity of HBV Pol in regulation of L1 retrotransposition.
Spatial point pattern analysis identifies mechanisms shaping the skin parasite landscape inLeishmania donovaniinfection
Authors: Doehl Johannes S. P. , Ashwin Helen , Brown Najmeeyah , Romano Audrey , Carmichael Samuel , Pitchford Jon W. , Kaye Paul M.
Published: May 2021

Increasing evidence suggests that infectiousness of hosts carrying parasites of theLeishmania donovanicomplex, the causative agents of visceral leishmaniasis, is linked to parasite repositories in the host skin. However, a detailed understanding of the dispersal and dispersion of these obligatory-intracellular parasites and their host phagocytes in the skin is lacking. Using endogenously fluorescent parasites as a proxy, we apply image analysis combined with spatial point pattern models borrowed from ecology to characterize dispersion of parasitized myeloid cells (including ManR+and CD11c+cells) and predict dispersal mechanisms in a previously described immunodeficient model ofL. donovaniinfection. Our results suggest that after initial seeding of infection in the skin, heavily parasite-infected myeloid cells are found in patches that resemble innate granulomas. Spread of parasites from these initial patches subsequently occurs through infection of recruited myeloid cells, ultimately leading to self-propagating networks of patch clusters. This combination of imaging and ecological pattern analysis to identify mechanisms driving the skin parasite landscape offers new perspectives on myeloid cell behavior following parasitism byL. donovaniand may also be applicable to elucidating the behavior of other intracellular tissue-resident pathogens and their host cells.
Characterization of the emerging B.1.621 variant of interest of SARS-CoV-2
Authors: Laiton-Donato Katherine , Franco-Muñoz Carlos , Álvarez-Díaz Diego A. , Ruiz-Moreno Hector Alejandro , Usme-Ciro José A. , Andrés Prada Diego , Reales-González Jhonnatan , Corchuelo Sheryll , Herrera-Sepúlveda María T. , Naizaque Julian , Santamaría Gerardo , Rivera Jorge , Rojas Paola , Hernández Ortiz Juan , Cardona Andrés , Malo Diana , Prieto-Alvarado Franklin , Gómez Fernando Ruiz , Wiesner Magdalena , Ospina Martínez Martha Lucia , Mercado-Reyes Marcela
Published: May 2021

The genetic diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to impact the virus transmissibility and the escape from natural infection- or vaccine-elicited neutralizing antibodies. Here, representative samples from circulating SARS-CoV-2 in Colombia between January and April 2021, were processed for genome sequencing and lineage determination following the nanopore amplicon ARTIC network protocol and PANGOLIN pipeline. This strategy allowed us to identify the emergence of the B.1.621 lineage, considered a variant of interest (VOI) with the accumulation of several substitutions affecting the Spike protein, including the amino acid changes T95I, Y144T, Y145S and the insertion 146N in the N-terminal domain, R346K, E484K and N501Y in the Receptor-binding Domain (RBD) and P681H1 in the S1/S2 cleavage site of the Spike protein. The rapid increase in frequency and fixation in a relatively short time in Magdalena, Atlántico, Bolivar, Bogotá D.C, and Santander that were near the theoretical herd immunity suggests an epidemiologic impact. Further studies will be required to assess the biological and epidemiologic roles of the substitution pattern found in the B.1.621 lineage.

Highlights

Monitoring the emergence of new variants of SARS-CoV-2 in real time is a worldwide priority.

Emerging variants of SARS-CoV-2 may have high impact biological implications for public health

The SARS-CoV-2 B.1.621 variant of interest was characterized by several substitutions: T95I, Y144T, Y145S, ins146N, R346K, E484K, N501Y and P681H in spike protein.
In vivoimaging of cannabinoid type 2 receptors, functional and structural alterations in mouse model of cerebral ischemia by PET and MRI
Authors: Ni Ruiqing , Müller Herde Adrienne , Haider Ahmed , Keller Claudia , Louloudis Georgios , Vaas Markus , Schibli Roger , Ametamey Simon M. , Klohs Jan , Mu Linjing
Published: May 2021

Background and purpose

Brain ischemia is one of the most important pathologies of the central nervous system. Non-invasive molecular imaging methods have the potential to provide critical insights into the temporal dynamics and follow alterations of receptor expression and metabolism in ischemic stroke. The aim of this study was to assess the cannabinoid type 2 receptors (CB2R) levels in transient middle cerebral artery occlusion (tMCAO) mouse models at subacute stage using positron emission tomography (PET) with our novel tracer [18F]RoSMA-18-d6, and structural imaging by magnetic resonance imaging (MRI).

Methods

Our recently developed CB2R PET tracer [18F]RoSMA-18-d6 was used for imaging the neuroinflammation at 24 h after reperfusion in tMCAO mice. The RNA expression levels of CB2R and other inflammatory markers were analyzed by quantitative real-time polymerase chain reaction using brain tissues from tMCAO (1 h occlusion) and sham-operated mice. [18F]fluorodeoxyglucose (FDG) was included for evaluation of the cerebral metabolic rate of glucose (CMRglc). In addition, diffusion-weighted imaging and T2-weighted imaging were performed for anatomical reference and delineating the lesion in tMCAO mice.

Results

mRNA expressions of inflammatory markersTNF-α,Iba1, MMP9andGFAP, CNR2were increased at 24 h after reperfusion in the ipsilateral compared to contralateral hemisphere of tMCAO mice, while mRNA expression of the neuronal markerMAP-2was markedly reduced. Reduced [18F]FDG uptake was observed in the ischemic striatum of tMCAO mouse brain at 24 h after reperfusion. Although higher activity of [18F]RoSMA-18-d6 inex-vivobiodistribution studies and higher standard uptake value ratio (SUVR) were detected in the ischemic ipsilateral compared to contralateral striatum in tMCAO mice, thein-vivospecificity of [18F]RoSMA-18-d6 was confirmed only in the CB2R-rich spleen.

Conclusions

This study revealed an increased [18F]RoSMA-18-d6 measure of CB2R and a reduced [18F]FDG measure of CMRglc in ischemic striatum of tMCAO mice at subacute stage. [18F]RoSMA-18-d6 might be a promising PET tracer for detecting CB2R alterations in animal models of neuroinflammation without neuronal loss.
AutoVEM2: a flexible automated tool to analyze candidate key mutations and
epidemic trends for virus
Authors: Xi Binbin , Li Shuhua , Liu Wei , Jiang Dawei , Bai Yunmeng , Qu Yimo , Lon Jerome Rumdon , Huang Lizhen , Du Hongli
Published: May 2021

In our previous work, we developed an automated tool, AutoVEM, for real-time
monitoring the candidate key mutations and epidemic trends of SARS-CoV-2. In
this research, we further developed AutoVEM into AutoVEM2. AutoVEM2 is composed
of three modules, including call module, analysis module, and plot module, which
can be used modularly or as a whole for any virus, as long as the corresponding
reference genome is provided. Therefore, it’s much more flexible than AutoVEM.
Here, we analyzed three existing viruses by AutoVEM2, including SARS-CoV-2, HBV
and HPV-16, to show the functions, effectiveness and flexibility of AutoVEM2. We
found that the N501Y locus was almost completely linked to the other 16 loci in
SARS-CoV-2 genomes from the UK and Europe. Among the 17 loci, 5 loci were on the
S protein and all of the five mutations cause amino acid changes, which may
influence the epidemic traits of SARS-CoV-2. And some candidate key mutations of
HBV and HPV-16, including T350G of HPV-16 and C659T of HBV, were detected. In
brief, we developed a flexible automated tool to analyze candidate key mutations
and epidemic trends for any virus, which would become a standard process for
virus analysis based on genome sequences in the future.

Highlights

An automatic tool to quickly analyze candidate key mutations and
epidemic trends for any virus was developed.

Our integrated analysis method and tool could become a standard
process for virus mutation and epidemic trend analysis based on
genome sequences in the future.

N501Y with the other 16 highly linked mutation sites of
SARS-CoV-2 in the UK and Europe were further confirmed, and some
valuable mutation sites of HBV and HPV-16 were detected.
Clone decomposition based on mutation signatures provides novel insights into mutational processes
Authors: Matsutani Taro , Hamada Michiaki
Published: May 2021

Intra-tumor heterogeneity is a phenomenon in which mutation profiles differ from cell to cell within the same tumor and is observed in almost all tumors. Understanding intra-tumor heterogeneity is essential from the clinical perspective. Numerous methods have been developed to predict this phenomenon based on variant allele frequency. Among the methods, CloneSig models the variant allele frequency and mutation signatures simultaneously and provides an accurate clone decomposition. However, this method has limitations in terms of clone number selection and modeling. We propose SigTracer, a novel hierarchical Bayesian approach for analyzing intra-tumor heterogeneity based on mutation signatures to tackle these issues. We show that SigTracer predicts more reasonable clone decompositions than the existing methods that use artificial data that mimic cancer genomes. We applied SigTracer to whole-genome sequences of blood cancer samples. The results were consistent with past findings that single base substitutions caused by a specific signature (previously reported as SBS9) related to the activation-induced cytidine deaminase intensively lie within immunoglobulin-coding regions for chronic lymphocytic leukemia samples. Furthermore, we showed that this signature mutates regions responsible for cell-cell adhesion. Accurate assignments of mutations to signatures by SigTracer can provide novel insights into signature origins and mutational processes.
The distinct role of ALDH1A1 and ALDH1A3 in the regulation of prostate cancer metastases
Authors: Gorodetska Ielizaveta , Offermann Anne , Püschel Jakob , Lukiyanchuk Vasyl , Gaete Diana , Kurzyukova Anastasia , Labitzky Vera , Schwarz Franziska , Lange Tobias , Knopf Franziska , Wielockx Ben , Krause Mechthild , Perner Sven , Dubrovska Anna
Published: May 2021

Cancer stem cells (CSC) are characterized by high self-renewal capacity, tumor-initiating potential, and therapy resistance. Aldehyde dehydrogenase (ALDH)+ cell population serves as an indicator of prostate CSCs with increased therapy resistance, enhanced DNA double-strand break repair, and activated epithelial-mesenchymal transition (EMT) and migration. Numerous ALDH genes contribute to ALDH enzymatic activity; however, only some of them showed clinical relevance. We found that ALDH1A1 and ALDH1A3 genes functionally regulate CSC properties and radiation sensitivity of PCa. We revealed a negative correlation between ALDH1A1 and ALDH1A3 expression in publicly available prostate cancer (PCa) datasets and demonstrated that ALDH1A1 and ALDH1A3 have opposing predictive value for biochemical recurrence-free survival. Our data suggest an association of ALDH1A1 with the metastatic burden, elucidating the role of ALDH genes in the metastatic spread and homing to the bone, which can be, at least partially, attributed to regulating the transforming growth factor beta 1 (TGFB1) and matrix metalloproteinases (MMPs). ALDH genes play a diverse role in PCa development under AR and β-catenin-dependent regulation, with ALDH1A1 becoming dominant in later stages of tumor development when PCa cells gain androgen independence. Taken together, our results indicate that ALDH1A1 and ALDH1A3 modulate PCa radiosensitivity, regulate CSCs phenotype, and spread of PCa cells to the bone, therefore having clinical implication for identifying patients at high risk for progression to metastatic disease.
Osteoblast cell death triggers a pro-osteogenic inflammatory response regulated by reactive oxygen species and glucocorticoid signaling in zebrafish
Authors: Geurtzen Karina , Duseja Ankita , Knopf Franziska
Published: May 2021

In zebrafish, transgenic labeling approaches, robust regenerative responses and excellentin vivoimaging conditions enable precise characterization of immune cell behavior in response to injury. Here, we monitored osteoblast-immune cell interactions in bone, a tissue which is particularly difficult toin vivoimage in tetrapod species. Ablation of individual osteoblasts leads to recruitment of neutrophils and macrophages in varying numbers, depending on the extent of the initial insult, and initiates generation ofcathepsinK+ osteoclasts from macrophages. Induced osteoblast death triggers the production of pro-inflammatory cytokines and reactive oxygen species, which are needed for successful macrophage recruitment. Excess glucocorticoid signaling as it occurs during the stress response inhibits macrophage recruitment, maximum speed and changes the macrophages’ phenotype. While osteoblast loss is compensated for within a day by contribution of committed osteoblasts, macrophages continue to populate the region. Their presence is required for osteoblasts to fill the lesion site. Our model enables visualization of homeostatic bone repair after microlesions at single cell resolution and demonstrates a pro-osteogenic function of tissue-resident macrophages in non-mammalian vertebrates.

Summary statement

Laser-mediated osteoblast ablation induces recruitment of tissue-resident macrophages by a release of reactive oxygen species. The presence of macrophages is required for osteoblasts to repopulate the lesion site and can be modulated by glucocorticoids.
Visual Field Analysis: a reliable method to score left- and right eye-use using automated tracking
Authors: Josserand Mathilde , Rosa-Salva Orsola , Versace Elisabetta , Lemaire Bastien S.
Published: May 2021

Brain and behavioural asymmetries have been documented in various taxa. Many of these asymmetries involve preferential left- and right-eye use. However, measuring eye use through manual frame-by-frame analyses from video recordings is laborious and may lead to biases. Recent progress in technology allowed the development of accurate tracking techniques for measuring animal behaviour. Amongst these techniques, DeepLabCut, a python-based tracking toolbox using transfer learning with deep neural networks, offers the possibility to track different body parts with unprecedented accuracy. Exploiting the potentialities of DeepLabCut, we developed ‘Visual Field Analysis’, an additional open-source application for extracting eye-use data. To our knowledge, this is the first application that can automatically quantify left-right preferences in eye use. Here we test the performance of our application in measuring preferential eye-use in young domestic chicks. The comparison with manual scoring methods revealed a perfect correlation in the measures of eye-use obtained by ‘Visual Field Analysis’. With our application, eye-use can be analysed reliably, objectively and at a fine scale in different experimental paradigms.
Oligomannosylation and MAN1A1 expression associate strongly with a subset of human cancer types
Authors: Chatterjee Sayantani , Kawahara Rebeca , Ugonotti Julian , Lee Ling Y. , Everest-Dass Arun , Thaysen-Andersen Morten
Published: May 2021

Aberrant protein glycosylation is a prominent cancer feature. While many tumour-associated glycoepitopes have been reported, advances in glycoanalytics continue to uncover new associations between glycoproteins and cancer. Guided by a comprehensive literature survey suggesting that oligomannosylation (Man5-9GlcNAc2, M5-M9) is a widespread albeit poorly studied glyco-signature in human cancers, we here re-visit a valuable compilation of nearly 500 LC-MS/MSN-glycomics datasets acquired across 11 human cancer types to systematically test for oligomannose-cancer associations. Firstly, our quantitative glycomics data obtained across 34 cancerous cell lines demonstrated that oligomannosylation, particularly the under-processed M7-M9, is a strong pan-cancer feature. We then showed cell surface expression of oligomannosidic epitopes in the promyelocytic leukemic HL-60 cell line using concanavalin A-based flow cytometry. In keeping with literature, our quantitative glycomics data of tumour and matching control tissues and new MALDI-MS imaging data of tissue microarrays showed a strong cancer-associated elevation of oligomannosylation in both basal cell (p= 1.78 x 10-12) and squamous cell (p= 1.23 x 10-11) skin cancer and colorectal cancer (p= 8.0 x 10-4). The glycomics data also indicated that few cancer types including gastric and liver cancer exhibit unchanged or reduced oligomannose levels, observations also supported by literature and MALDI-MSI. Finally, data from cancer repositories indicated that three α1,2-mannosidases dictate oligomannose expression in cancer cells, and further suggested that deleterious mutations and reduced expression of MAN1A1 are key contributors to the cancer-associated oligomannose elevation. Collectively, these findings open hitherto unexplored avenues for the development of new cancer biomarkers and therapeutic targets.
Live imaging of delamination inDrosophilashows epithelial cell motility and invasiveness are independently regulated
Authors: Inaki Mikiko , Matsuno Kenji
Published: May 2021

Delaminating cells undergo complex, precisely regulated changes in cell-cell adhesion, motility, polarity, invasiveness, and other cellular properties. Delamination occurs during development and in pathogenic conditions such as cancer metastasis. We analyzed the requirements for epithelial delamination inDrosophilaovary border cells, which detach from the structured epithelial layer and begin to migrate collectively. We used live imaging to examine cellular dynamics, particularly epithelial cells’ acquisition of motility and invasiveness, in delamination-defective mutants during the time period in which delamination occurs in the wild-type ovary. We found that border cells inslow border cells(slbo), a delamination-defective mutant, lacked invasive cellular protrusions but acquired motility, while JAK/STAT-inhibited border cells lost both invasiveness and motility. Our results indicate that invasiveness and motility, which are cooperatively required for delamination, are regulated independently. Our reconstruction experiments also showed that motility is not a prerequisite for acquiring invasiveness.

Summary statement

Live imaging of epithelial delamination reveals that cell motility and invasiveness, both of which are required for delamination, are regulated independently and that motility is not a prerequisite for invasiveness.
Comparing the effectiveness of secondary distribution of HIV self-testing to testing card referral in promoting HIV testing among men who have sex with men in China: A quasi-experimental study
Authors: Sha Yongjie , Xiong Yuan , Wang Yehua , Ong Jason , Ni Yuxin , Lu Ying , Cheng Mengyuan , Tucker Joseph , Tang Weiming
Published: May 2021

Background

Social network-based HIV self-testing (HIVST) is useful to promote HIV testing. Secondary distribution is one social network-based method whereby individuals (indexes) access multiple HIVST kits and distribute them to their social networks (alters). This quasi-experimental study compared the effectiveness and cost of two social network-based HIV testing strategies (HIVST secondary distribution and HIV testing card referral) in promoting HIV testing among Chinese men who have sex with men (MSM).

Methods

MSM aged 18 years or older were recruited in Guangzhou, Guangdong Province. From May to September 2019, indexes recruited during that period could distribute HIVST kits to people within their social network. Indexes recruited from October 2019 to January 2020 could refer HIV testing cards to people within their social network for free facility-based tests. Participants could access 1-5 HIVST kits or testing referral cards for distribution. Alters were encouraged to upload a picture of their test results and complete an online survey. Indexes and alters received an incentive to report test results.

Results

Two hundred thirty-nine potential participants were assessed for eligibility and 208/245 (84.9%) were eligible. Among those who completed baseline assessment, 154/208 (74.0%) completed one month of follow-up. Overall,106 indexes were recruited in the HIVST arm and 102 in the testing card arm. The two arms had similar socio-demographic characteristics. At the one-month follow-up, 92 indexes in the HIVST arm self-reported having distributed self-test kits to 179 unique alters, and 62 in the testing card arm self-reported having distributed testing referral cards to 26 unique alters. Additionally, 69/92 (75%) in the HIVST arm distributed any test to friends or sexual partners compared to 18/62 (29%) in the testing card arm, with a risk difference of 46% (95% CI 31%, 61%). Indexes in the HIVST arm distributed an average of 1.95 (SD=1.90) tests, compared to 0.42 (SD=0.78) in the testing card arm, with a risk difference of 1.53 (95% CI 1.09, 1.96). Subgroup analysis suggested that indexes in the HIVST arm who self-identified as gay (p = 0.007) or were previously tested for HIV (p = 0.02) were more likely to distribute. The HIVST arm had a higher total cost and higher testing coverage compared to the testing card referral arm. The ICER per alter tested was $52.78.

Conclusions

Secondary distribution of HIVST engaged more MSM to distribute tests to their social network and reached more MSM for test. MSM who self-identify as gay or who have previously tested for HIV were more effective in distributing tests. Future testing approaches should include HIVST kits in voluntary counselling and testing settings and incorporate digital strategies for secondary distribution.
Two functionally distinct Purkinje cell populations implement an internal model within a single olivo-cerebellar loop
Authors: Angelaki Dora E. , Laurens Jean
Published: May 2021

Olivo-cerebellar loops, where anatomical patches of the cerebellar cortex and inferior olive project one onto the other, form an anatomical unit of cerebellar computation. Here, we investigated how successive computational steps map onto olivo-cerebellar loops. Lobules IX-X of the cerebellar vermis, i.e. the nodulus and uvula, implement an internal model of the inner ear’s graviceptor, the otolith organs. We have previously identified two populations of Purkinje cells that participate in this computation: Tilt-selective cells transform egocentric rotation signals into allocentric tilt velocity signals, to track head motion relative to gravity, and translation-selective cells encode otolith prediction error. Here we show that, despite very distinct simple spike response properties, both types of Purkinje cells emit complex spikes that are proportional to sensory prediction error. This indicates that both cell populations comprise a single olivo-cerebellar loop, in which only translation-selective cells project to the inferior olive. We propose a neural network model where sensory prediction errors computed by translation-selective cells are used as a teaching signal for both populations, and demonstrate that this network can learn to implement an internal model of the otoliths.
Meiofauna is an important, yet neglected, component of biodiversity ofPosidonia oceanica
Authors: García-Gómez Guillermo , García-Herrero Álvaro , Sánchez Nuria , Pardos Fernando , Izquierdo-Muñoz Andrés , Fontaneto Diego , Martínez Alejandro
Published: May 2021

Posidonia oceanicameadows are biodiversity reservoirs and provide many ecosystem services in coastal Mediterranean regions. Marine meiofauna, on the other hand, not only represents a major component of regional marine biodiversity, but also a useful tool to address both theoretical and applied questions in ecology, evolution, and conservation. We review the meiofaunal diversity in theP. oceanicaecosystem combining a literature review and a case study. First, we gathered records of 664 species from 69 published studies as well as unpublished sources, including few species exclusive from this ecosystem. Eighteen of those studies quantified the spatial and temporal changes of species composition, highlighting habitat-specific assemblages that fluctuate following the annual changes experienced byP. oceanica. Hydrodynamics, habitat complexity, and food availability, all three inherently linked to the seagrass phenology, are recognised as the main factors at shaping the complex distribution patterns of meiofauna in the meadows. These drivers have been identified mainly from Copepoda and Nematoda, and depend ultimately on species-specific preferences. Second, we tested the generality of these observations using marine mites as a model group, showing that the same processes might be in place also for other less abundant meiofaunal groups. Overall, our study highlights an outstanding diversity of meiofauna inP. oceanicaand shows its potential for future research, not only focused on exploring and describing new species of neglected meiofaunal organisms, but also providing a more complete understanding on the functioning of the iconic Mediterranean ecosystem created byP. oceanica.
Protein phosphatase 1 regulatory inhibitor subunit 14C promotes triple-negative breast cancer progression via sustaining inactive glycogen synthase kinase 3 beta
Authors: Jian Yunting , Kong Lingzhi , Xu Hongyi , Huang Xinjian , Li Yue , Shi Dongni , Xiao Yunyun , Yang Muwen , Li Siqi , Chen Xiangfu , Ouyang Ying , Hu Yameng , Chen Xin , Liu Pian , Wei Weidong
Published: May 2021

The majority of clinical deaths among patients with triple-negative breast cancer (TNBC) are caused by uncontrolled cell proliferation and aggressive metastases, which is regulated by hyperactive glycogen synthase kinase 3 beta (GSK3β); however, the underlying mechanisms remain largely unknown. In the present study, we found that protein phosphatase 1 regulatory inhibitor subunit 14C (PPP1R14C) was specifically upregulated in TNBC, compared with that in normal tissues and non-TNBC. High PPP1R14C expression correlated significantly with shorter 5-year relapse-free survival and overall survival in patients with TNBC. Overexpressing PPP1R14C promoted, while suppression of PPP1R14C decreased the cell proliferation and the aggressive phenotype of TNBC cells, in vitro and in vivo. Importantly, we revealed that PPP1R14C interacted with and inactivated type 1 Ser/Thr protein phosphatase (PP1) to sustain GSK3β phosphorylation at S9, and induced the ubiquitylation and degradation of non-phosphorylated GSK3β (S9A) via recruiting E3 ligase, TRIM25. Furthermore, treating with C2 ceramide (C2), which recovered kinase activity of GSK3β, resulted in tumor growth inhibition in PPP1R14C-overexpressing TNBC cells. Our findings reveal a novel mechanism whereby PPP1R14C sustains inactive GSK3β, which might lead to targeted therapy for TNBC.
Transcriptomic Insights into the Responses in Leaves Storing Lipid Organelles under Different Irradiances
Authors: Winichayakul Somrutai , Macknight Richard , Beechey-Gradwell Zac , Lee Robyn , Xue Hong , Crowther Tracey , Anderson Philip , Richardson Kim , Zou Xiuying , Maher Dorothy , Brock Shona , Cooney Luke , Bryan Gregory , Roberts Nick
Published: May 2021

To increase the nutritional value of forage, transgenic ryegrass known asHighMetabolizableEnergy (HME) were previously generated that co-express cysteine-oleosin and diacylglycerol O-acyltransferase. HME not only accumulate lipids in the leaf but also has elevated CO2assimilation and increased biomass. Shading is one of the most influencing factors for ryegrass growth environments particularly in swards. The aim of this study, therefore, was to determine the influence of irradiance levels on photosynthesis and gene expression in the HME leaves when compared with their corresponding non-transformant (NT). Under low light (150-250 µmol m-2s-1) and standard light (600-1000 µmol m-2s-1), the HME accumulated more lipid than NT. The previously reported elevated photosynthesis and increased biomass was observed when the HME were grown under standard light but not under low light. Under both light conditions, compared to NT, the HME had upregulated a number of transcripts involved in lipid metabolism, light capturing, photosynthesis, and sugar signalling network while downregulated genes participated in sugar and fructan biosynthesis. We further discuss how the HME differentially manipulated several genes other metabolic pathways including maintenance of redox homeostasis. Combined, the data suggests that the increased photosynthesis capacity in the HME likely corresponds to an increase of micro-lipid sink strength; these are influenced by available light energy and may be related to diffusional and biochemical activities of stomata. Overall, this work provides a clearly understanding of the changes in molecular and biochemical mechanisms underlying the carbon storing as leaf lipid sink of the HME ryegrass.

One sentence summary

Shading led to increase leaf lipid accumulation but limit the greater photosynthesis trait of high lipid ryegrass which may be related to limitation of biochemical activities of stomata.
RNA virome diversity andWolbachiainfection in individualDrosophila simulansflies
Authors: Ortiz-Baez Ayda Susana , Shi Mang , Hoffmann Ary A. , Holmes Edward C.
Published: May 2021

The endosymbiont bacteriumWolbachiais associated with multiple mutualistic effects on insect biology, including nutritional and antiviral properties.Wolbachianaturally occurs inDrosophilafly species, providing an operational model host to study how virome composition may be impacted by its presence.Drosophila simulanspopulations can carry a variety ofWolbachiastrains. In particular, thewAu strain ofWolbachiahas been associated with strong antiviral protection under experimental conditions. We usedD. simulanssampled from the Perth Hills, Western Australia, to investigate the potential virus protective effect of thewAu strain on individual wild-caught flies. Our data revealed no appreciable variation in virus composition and abundance betweenWolbachiainfected/uninfected individuals associated with the presence/absence ofwAu. However, it remains unclear whetherwAu might impact viral infection and host survival by increasing tolerance rather than inducing complete resistance. These data also provide new insights into the natural virome diversity ofD. simulans. Despite the small number of individuals sampled, we identified a repertoire of RNA viruses, including Nora virus, Galbut virus, Chaq virus, Thika virus and La Jolla virus, that have been identified in otherDrosophilaspecies. In addition, we identified five novel viruses from the familiesReoviridae,Tombusviridae,MitoviridaeandBunyaviridae.Overall, this study highlights the complex interaction betweenWolbachiaand RNA virus infections and provides a baseline description of the natural virome ofD. simulans.
An Artificial Neural-Network Approach for Motor Hotspot Identification Based on Electroencephalography: A Proof-of-Concept Study
Authors: Choi Ga-Young , Han Chang-Hee , Lee Hyung-Tak , Paik Nam-Jong , Kim Won-Seok , Hwang Han-Jeong
Published: May 2021

Background

To apply transcranial electrical stimulation (tES) to the motor cortex, motor hotspots are generally identified using motor evoked potentials by transcranial magnetic stimulation (TMS). The objective of this study is to validate the feasibility of a novel electroencephalography (EEG)-based motor-hotspot-identification approach using a machine learning technique as a potential alternative to TMS.

Methods

EEG data were measured using 63 channels from thirty subjects as they performed a simple finger tapping task. Power spectral densities of the EEG data were extracted from six frequency bands (delta, theta, alpha, beta, gamma, and full) and were independently used to train and test an artificial neural network for motor hotspot identification. The 3D coordinate information of individual motor hotspots identified by TMS were quantitatively compared with those estimated by our EEG-based motor-hotspot-identification approach to assess its feasibility.

Results

The minimum mean error distance between the motor hotspot locations identified by TMS and our proposed motor-hotspot-identification approach was 0.22 ± 0.03 cm, demonstrating the proof-of-concept of our proposed EEG-based approach. A mean error distance of 1.32 ± 0.15 cm was measured when using only nine channels attached to the middle of the motor cortex, showing the possibility of practically using the proposed motor-hotspot-identification approach based on a relatively small number of EEG channels.

Conclusion

We demonstrated the feasibility of our novel EEG-based motor-hotspot-identification method. It is expected that our approach can be used as an alternative to TMS for motor hotspot identification. In particular, its usability would significantly increase when using a recently developed portable tES device integrated with an EEG device.
TAP: Targeting and analysis pipeline for optimization and verification of coil placement in transcranial magnetic stimulation
Authors: Dannhauer Moritz , Huang Ziping , Beynel Lysianne , Wood Eleanor , Bukhari-Parlakturk Noreen , Peterchev Angel V.
Published: May 2021

Objective

Transcranial magnetic stimulation (TMS) can modulate brain function via an electric field (E-field) induced in a brain region of interest (ROI). The ROI E-field can be computationally maximized and set to match a specific reference using individualized head models to find the optimal coil placement and stimulus intensity. However, the available software lacks many practical features for prospective planning of TMS interventions and retrospective evaluation of the experimental targeting accuracy.

Approach

The TMS targeting and analysis pipeline (TAP) software uses an MRI/fMRI-derived brain target to optimize coil placement considering experimental parameters such as the subject’s hair thickness and coil placement restrictions. The coil placement optimization is implemented in SimNIBS 3.2, for which an additional graphical user interface (TargetingNavigator) is provided to visualize/adjust procedural parameters. The coil optimization process also computes the E-field at the target, allowing the selection of the TMS device intensity setting to achieve specific E-field strengths. The optimized coil placement information is prepared for neuronavigation software, which supports targeting during the TMS procedure. The neuronavigation system can record the coil placement during the experiment, and these data can be processed in TAP to quantify the accuracy of the experimental TMS coil placement and induced E-field.

Main results

TAP was demonstrated in a study consisting of three repetitive TMS sessions in five subjects. TMS was delivered by an experienced operator under neuronavigation with the computationally optimized coil placement. Analysis of the experimental accuracy from the recorded neuronavigation data indicated coil location and orientation deviations up to about 2 mm and 2°, respectively, resulting in an 8% median decrease in the target E-field magnitude compared to the optimal placement.

Significance

TAP supports navigated TMS with a variety of features for rigorous and reproducible stimulation delivery, including planning and evaluation of coil placement and intensity selection for E-field-based dosing.
Can charge-reversal be considered as a strategy for attaining thermal stability in proteins?
Authors: Hait Suman , Basu Sudipto , Kundu Sudip
Published: May 2021

Do charge reversal mutations (CRM) naturally occur in mesophilic-thermophilic/hyperthermophilic (M-T/HT) orthologous proteins? Do they contribute to thermal stability by altering charge-charge interactions? A careful investigation on 1550 M-T/HT orthologous protein pairs with remarkable structural and topological similarity extracts the role of buried and partially exposed CRMs in enhancing thermal stability. Our findings could assist in engineering thermo-stable variants of proteins.

SIGNIFICANCE

Protein engineering is one of the hot topics for decades specifically for its applications in different fields like de-novo protein design, directed evolution, making highly stable variants for food and drug industry etc. Proteins from organisms living in extreme environments are therefore a matter of common interest for scientists from different disciplines. Over three decades of study has already found several sequence and structural adaptations related to thermal stability, while charge reversal study remains ignored to a large extent. Influenced by nature’s strategy, our study provides a systemic understanding of how proper designing of few partially exposed and buried CRMs significantly contributes to thermal stability by altering the short distance electrostatic interactions.
Transdiagnostic phenotyping of psychopathology in a help-seeking population (PhenoNetz): A study protocol for an experience sampling study
Authors: Rosen Marlene , Betz Linda T. , Montag Christian , Kannen Christopher , Kambeitz Joseph
Published: May 2021

Prevention in psychiatry provides a promising way to address the burden by mental illness. However, established approaches focus on specific diagnoses and do not address the heterogeneity and manifold potential outcomes of help-seeking populations that present at early recognition services. Conceptualizing psychopathology manifested in help-seeking populations from a network perspective of interacting symptoms allows transdiagnostic investigations beyond binary disease categories. Furthermore, modern technologies such as smartphones facilitate the application of Experience Sampling Methods (ESM). A combination of ESM with network analyses provides valid insights beyond established assessment instruments. We will examine n = 75 individuals (age 18-40 years) of the help-seeking population of the Cologne early recognition centre (FETZ). For a maximally naturalistic sample, only minimal exclusion criteria will be applied. We will collect data for 14 days utilizing a mobile application to assess ten transdiagnostic symptoms, i.e., depressive, anxious and psychotic symptoms as well as distress level. With these data, we will generate average group-level symptom networks and personalized symptom networks using a two-step multilevel vector autoregressive model. Additionally, we will explore associations between symptom networks and sociodemographic, risk and resilience factors, as well as psychosocial functioning. Our study will provide insights about feasibility and utility of ESM in a help-seeking population. Providing a first explorative phenotyping of the transdiagnostic help-seeking population, this study will contribute to innovation of early recognition in psychiatry. Results will help to pave the way for prevention and targeted early intervention in a broader patient group and thus, enable greater intended effects in alleviating the burden of psychiatric disorders.
Establishment of CRISPR/Cas9-based knock-in in a hemimetabolous insect: targeted gene tagging in the cricketGryllus bimaculatus
Authors: Matsuoka Yuji , Nakamura Taro , Watanabe Takahito , Barnett Austen A. , Tomonari Sayuri , Ylla Guillem , Whittle Carrie A. , Noji Sumihare , Mito Taro , Extavour Cassandra G.
Published: May 2021

Studies of traditional model organisms like the fruit flyDrosophila melanogasterhave contributed immensely to our understanding of the genetic basis of developmental processes. However, the generalizability of these findings cannot be confirmed without functional genetic analyses in additional organisms. Direct genome editing using targeted nucleases has the potential to transform hitherto poorly-understood organisms into viable laboratory organisms for functional genetic study. To this end, here we present a method to induce targeted genome knock-out and knock-in of desired sequences in an insect that serves as an informative contrast toDrosophila, the cricketGryllus bimaculatus. The efficiency of germ line transmission of induced mutations is comparable to that reported for other well-studied laboratory organisms, and knock-ins targeting introns yield viable, fertile animals in which knock-in events are directly detectable by visualization of a fluorescent marker in the expression pattern of the targeted gene. Combined with the recently assembled and annotated genome of this cricket, this knock-in/knock-out method increases the viability ofG. bimaculatusas a tractable system for functional genetics in a basally branching insect.