bluuebunny/crossref_metadata_2025 huggingface dataset:
Granulomatosis with polyangiitis following Pfizer-BioNTech COVID-19 vaccination
Authors: Shirai Tsuyoshi , Suzuki Jun , Kuniyoshi Shimpei , Tanno Yuito , Fujii Hiroshi
Published: March 2022

We report the first case of proteinase 3-antineutrophil cytoplasmic antibody-positive granulomatosis with polyangiitis (GPA) with predominant ears, nose, and throat manifestations following coronavirus disease 2019 (COVID-19) vaccination. A 63-year-old woman presented with aural fullness 3 days after vaccination. She presented with progressive rhinosinusitis and otitis media leading to profound hearing loss within 3 weeks. Clinical imaging revealed soft-tissue shadows in the paranasal sinuses with multiple pulmonary nodules, and histopathology was consistent with a diagnosis of GPA. It is crucial to be wary of the possibility of GPA in patients who received COVID-19 vaccines due to its rapid disease progression.
Systemic lupus erythematosus and antiphospholipid syndrome after COVID-19 vaccination. A case report
Authors: Molina-Rios Sebastian , Rojas-Martinez Rigoberto , Estévez-Ramirez Gloria Marcela , Medina Yimy Francisco
Published: March 2022

Coronavirus disease 2019 (COVID-19) vaccines have some adverse effects, mostly mild. However, by presenting an immunological challenge to the individual, they could infrequently trigger immune-mediated diseases (IMDs). We report the case of a 42-year-old woman, with no previous medical history, who received the first dose of vaccine against COVID-19 and developed inflammatory arthralgias, associated with sudden-onset dyspnoea and hypoxemia. Pulmonary thromboembolism was documented, and the diagnosis of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) was suspected. Autoantibodies were measured confirming this suspicion. After a few days, she presented a massive pericardial effusion with cardiac tamponade that required surgical management. Treatment with azathioprine, hydroxychloroquine, corticosteroids, and anticoagulation was indicated with improvement of all her symptoms. There is controversy regarding the potential of COVID-19 vaccines to induce autoimmunity. Studies addressing the safety of using these vaccines have reported the occurrence of mild local and systemic reactions, most frequently in young adults. So far, there are few reports of patients who have developed autoimmune or autoinflammatory diseases after getting vaccinated with any of the COVID-19 vaccines. To the best of our knowledge, to date, this is one of the first cases of new-onset SLE and secondary APS after COVID-19 vaccination.
Chromatin landscape associated with sexual differentiation in a UV sex determination system
Authors: Gueno Josselin , Borg Michael , Bourdareau Simon , Cossard Guillaume , Godfroy Olivier , Lipinska Agnieszka , Tirichine Leila , Cock J Mark , Coelho Susana M
Published: March 2022

In many eukaryotes, such as dioicous mosses and many algae, sex is determined by UV sex chromosomes and is expressed during the haploid phase of the life cycle. In these species, the male and female developmental programs are initiated by the presence of the U- or V-specific regions of the sex chromosomes but, as in XY and ZW systems, sexual differentiation is largely driven by autosomal sex-biased gene expression. The mechanisms underlying the regulation of sex-biased expression of genes during sexual differentiation remain elusive. Here, we investigated the extent and nature of epigenomic changes associated with UV sexual differentiation in the brown alga Ectocarpus, a model UV system. Six histone modifications were quantified in near-isogenic lines, leading to the identification of 16 chromatin signatures across the genome. Chromatin signatures correlated with levels of gene expression and histone PTMs changes in males versus females occurred preferentially at genes involved in sex-specific pathways. Despite the absence of chromosome scale dosage compensation and the fact that UV sex chromosomes recombine across most of their length, the chromatin landscape of these chromosomes was remarkably different to that of autosomes. Hotspots of evolutionary young genes in the pseudoautosomal regions appear to drive the exceptional chromatin features of UV sex chromosomes.
Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network duringPlasmodium falciparumblood-stage development
Authors: Shang Xiaomin , Wang Changhong , Fan Yanting , Guo Gangqiang , Wang Fei , Zhao Yuemeng , Sheng Fei , Tang Jianxia , He Xiaoqin , Yu Xinyu , Zhang Meihua , Zhu Guoding , Yin Shigang , Mu Jianbing , Culleton Richard , Cao Jun , Jiang Mei , Zhang Qingfeng
Published: March 2022

Heterochromatin-associated gene silencing controls multiple physiological processes in malaria parasites, however, little is known concerning the regulatory network and cis-acting sequences involved in the organization of heterochromatin and how they modulate heterochromatic gene expression. Based on systematic profiling of genome-wide occupancy of eighteen Apicomplexan AP2 transcription factors by ChIP-seq analysis, we identify and characterize eight heterochromatin-associated factors (PfAP2-HFs), which exhibit preferential enrichment within heterochromatic regions but with differential coverage profiles. Although these ApiAP2s target euchromatic gene loci via specific DNA motifs, they are likely integral components of heterochromatin independent of DNA motif recognition. Systematic knockout screenings of ApiAP2 factors coupled with RNA-seq transcriptomic profiling revealed three activators and three repressors of heterochromatic gene expression including four PfAP2-HFs. Notably, expression of virulence genes is either completely silenced or significantly reduced upon the depletion of PfAP2-HC. Integrated multi-omics analyses reveal autoregulation and feed-forward loops to be common features of the ApiAP2 regulatory network, in addition to the occurrence of dynamic interplay between local chromatin structure and ApiAP2s in transcriptional control. Collectively, this study provides a valuable resource describing the genome-wide landscape of the ApiAP2 family and insights into functional divergence and cooperation within this family during the blood-stage development of malaria parasites.
Retron reverse transcriptase termination and phage defense are dependent on host RNase H1
Authors: Palka Christina , Fishman Chloe B , Bhattarai-Kline Santi , Myers Samuel A , Shipman Seth L
Published: March 2022

Retrons are bacterial retroelements that produce single-stranded, reverse-transcribed DNA (RT-DNA) that is a critical part of a newly discovered phage defense system. Short retron RT-DNAs are produced from larger, structured RNAs via a unique 2′-5′ initiation and a mechanism for precise termination that is not yet understood. Interestingly, retron reverse transcriptases (RTs) typically lack an RNase H domain and, therefore, depend on endogenous RNase H1 to remove RNA templates from RT-DNA. We find evidence for an expanded role of RNase H1 in the mechanism of RT-DNA termination, beyond the mere removal of RNA from RT-DNA:RNA hybrids. We show that endogenous RNase H1 determines the termination point of the retron RT-DNA, with differing effects across retron subtypes, and that these effects can be recapitulated using a reduced, in vitro system. We exclude mechanisms of termination that rely on steric effects of RNase H1 or RNA secondary structure and, instead, propose a model in which the tertiary structure of the single-stranded RT-DNA and remaining RNA template results in termination. Finally, we show that this mechanism affects cellular function, as retron-based phage defense is weaker in the absence of RNase H1.
Novel Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Necrotizing Pneumonia Complicated by Empyema: A Case Report
Authors: Holger Dana J , Kunz Coyne Ashlan J , Zhao Jing J , Sandhu Avnish , Salimnia Hossein , Rybak Michael J
Published: March 2022

We report our clinical and laboratory experience treating a 50-year-old patient who was critically ill with extensively drug-resistant Acinetobacter baumannii necrotizing pneumonia complicated by empyema in Detroit, Michigan. A precision medicine approach using whole-genome sequencing, susceptibility testing, and synergy analysis guided the selection of rational combination antimicrobial therapy.
Cross-seasonal effects in the American Woodcock: Conditions prior to fall migration relate to migration strategy and implications for conservation
Authors: Graham Clayton L , Steeves Tanner , McWilliams Scott R
Published: March 2022

How postbreeding habitat quality and body composition of migratory birds carry over to influence fall migration strategies and residency merits consideration when creating cross-seasonal conservation plans, especially in breeding populations that are partial migrants. We assessed the influence of postbreeding habitat quality on departure body composition and fall migration patterns in a southern New England breeding population of American Woodcock (Scolopax minor). Woodcock that overwintered near breeding areas (n = 5) had less fat upon capture in fall and used lower quality habitat during the fall than birds that eventually departed on migration (n = 17). Woodcock that departed earlier were long-distance migrants that had inhabited higher quality landscapes prior to migration, departed with less or similar fat stores, stopped over for shorter periods on migration, and arrived earlier on their more southerly wintering areas. In contrast, woodcock that departed later were short-distance migrants that had inhabited lower quality landscapes prior to migration yet stored similar or more fat upon departure, stopped over for longer periods on migration, and arrived relatively late to their more northerly wintering areas. These differences in migration strategies were evident under the same fall environmental conditions and did not appear related to individuals responding to their own condition as would be expected if they were classic condition-based carry-over effects. As such, the southern New England breeding population of woodcock is best categorized as nonfacultative partial migrants (i.e., includes residents, short-distance migrants, and long-distance migrants) that demonstrate weak connectivity between life stages; such populations are excellent for the study of the costs and benefits of migration. The stopover and wintering areas used by woodcock in the coastal mid-Atlantic states deserve conservation and management attention in order to preserve critical habitat throughout their wintering range.
Improving the Measurement of Hostile Sexism
Authors: Archer Allison M N , Clifford Scott
Published: March 2022

In recent years, sexism has played an increasingly pivotal role in American politics, and scholarship examining the importance of gender attitudes for political behavior has surged. Researchers have largely relied on the hostile sexism scale to measure prejudice against women, and this scale seems particularly relevant to political science research. However, this scale measures attitudes with an agree-disagree response format, which has long been recognized as a source of substantial measurement error. In this paper, we introduce a revised version of the hostile sexism scale that instead relies on an item-specific question format. Across three studies, we show that the item-specific scale is strongly related to the agree-disagree scale, but that the item-specific version reduces problems with truncation and tends to improve discriminant and predictive validity. Given these advantages, we conclude by recommending that researchers adopt the item-specific hostile sexism scale.
Humoral response and safety of BNT162b2 mRNA vaccine in children with rheumatic diseases
Authors: Akgün Özlem , Çakmak Figen , Guliyeva Vafa , Demirkan Fatma Gül , Tanatar Ayşe , Hançerli Torun Selda , Çin Dilan , Meşe Sevim , Ağaçfidan Ali , Aktay Ayaz Nuray
Published: March 2022

Objectives

The coronavirus disease 2019 (COVID-19) vaccine represents a cornerstone in tackling the pandemic and with the approval of the BNT162b2 mRNA vaccine in December 2020, it has become a beacon of hope for people around the world, including children. This study aimed to present the data on the humoral response and safety of vaccine in a cohort of patients with paediatric rheumatic diseases receiving immunomodulatory treatments.

Methods

Forty-one children with paediatric rheumatic diseases were included and were vaccinated with the BNT162b2 mRNA vaccine (two doses of 30 µg administered 3–4 weeks apart). To assess the humoral response, IgG antibodies developed against the S1/Receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein at baseline and 3–4 weeks after the second dose were measured. The possible local and systemic side effects and disease activity scores were evaluated during the study period.

Results

After the second dose of vaccine, markedly elevated anti-RBD IgG titres were observed in all patients with a median titre of 20 474 AU/ml [interquartile range (IQR) 6534–36 151] with a good safety profile. The median disease duration was 4.3 (IQR 3.5–5.6) years. In the cohort, 14 (34.1%) received conventional DMARDs (cDMARDs), 16 (39%) received biologic DMARDs (bDMARDs) and 11 (26.8%) received a combined therapy (cDMARDs and bDMARDs). Patients treated with combined therapy [median 4695 (IQR 2764–26 491)] had significantly lower median titres of anti-RBD IgG than those receiving only cDMARDs.

Conclusion

Paediatric rheumatic diseases patients receiving immunomodulatory treatments were able to mount an effective humoral response after two dose regimens of BNT162b2 mRNA vaccine safely without interrupting their current treatments.
A systematic review of live vaccine outcomes in infants exposed to biologic disease modifying anti-rheumatic drugs in utero
Authors: Goulden Bethan , Chua Nicole , Parker Elaine , Giles Ian
Published: March 2022

Objectives

Transplacental passage of certain biologic and targeted synthetic DMARDs leads to detectable levels in the neonate, which may impact on the safety of live vaccines. Guidelines advise delaying live vaccine administration in biologic-exposed infants until they are 7 months old.

Methods

A systematic review of Embase, Medline and Cochrane identified live vaccine outcomes in infants exposed to biologic or targeted synthetic DMARDs in utero.

Results

Studies included 276 in utero exposures to adalimumab, certolizumab, etanercept, infliximab, golimumab, tocilizumab and ustekinumab. Live vaccine exposures at <12 months of age included Bacille Calmette-Guérin (BCG) (n = 215), rotavirus (n = 46), and measles, mumps and rubella (MMR) (n = 12). We identified no reactions following MMR, seven mild reactions to rotavirus vaccination and eight reactions to BCG, including one death. All infants with an adverse reaction to BCG had been exposed to infliximab in utero, and six had received BCG in the first month of life. A freedom of information request to the Medicines and Healthcare products Regulatory Agency revealed four fatal disseminated BCG infections in infants exposed to TNF inhibitors in utero, including infliximab, adalimumab and one unspecified TNF inhibitor.

Conclusion

Most evidence for a clinically harmful effect was for early administration of the BCG vaccine to infants exposed in utero to TNF inhibitors with high transplacental transfer rates.
Increased risk of rheumatoid arthritis in patients with endometriosis: genetic aspects
Authors: Zervou Maria I , Vlachakis Dimitrios , Papageorgiou Louis , Eliopoulos Elias , Goulielmos George N
Published: March 2022

RA is an inflammatory joint disease of an autoimmune nature, with a complex mode of inheritance characterized by chronic and destructive inflammation in the peripheral joints of the hands and feet and irreversible disability. This disorder occurs more often in women, and reproductive and hormonal factors have been shown to be related to increased risk. Endometriosis is a chronic, complex, oestrogen-dependent and progressive gynaecological disorder characterized by the growth of endometrial tissue outside the uterine cavity. Thus far, substantial abnormalities in the immune system of women with endometriosis have been demonstrated. Epidemiological data have suggested a link between endometriosis and the risk of incident RA. The similarities between molecular and cellular pathways of endometriosis and RA may implicate a partially shared genetic background. In this review we present an overview of the shared genetic factors known thus far that are associated with the development of both disorders.
Cluster analysis of upper airway stimulation adherence patterns and implications on clinical care
Authors: Soose Ryan J , Araujo Matheus , Faber Kevin , Roy Asim , Lee Kent , Ni Quan , Srivastava Jaideep , Strollo Patrick J
Published: March 2022

Study Objectives

Upper airway stimulation (UAS) therapy is effective for a subset of obstructive sleep apnea (OSA) patients with continuous positive airway pressure (CPAP) intolerance. While overall adherence is high, some patients have suboptimal adherence, which limits efficacy. Our goal was to identify therapy usage patterns during the first 3 months of therapy to enable targeted strategies for improved adherence.

Methods

Therapy data was retrieved from 2098 patients for three months after device activation. Data included mean and standard deviation (SD) of hours of use, therapy pauses, hours from midnight the therapy was turned ON and OFF, percentage of missing days, and stimulation amplitude. Cluster analysis was performed using Gaussian mixture models that categorized patients into six main groups.

Results

The six groups and their prevalence can be summarized as Cluster 1A: Excellent Use (34%); Cluster 1B: Excellent Use with variable timing (23%); Cluster 2A: Good Use with missing days and late therapy ON (16%), Cluster 2B: Good Use with missing days, late therapy ON, and early therapy OFF (12%); Cluster 3A: Variable Use with frequent missing days (8%); Cluster 3B: Variable Use with frequent pauses (7%). Most patients (85%) are excellent or good users with mean therapy use >6 hours per night.

Conclusions

Cluster analysis of early UAS usage patterns identified six distinct groups that may enable personalized interventions for improved long-term management. Differentiation of the patient clusters may have clinical implications with regard to sleep hygiene education, therapy discomfort, comorbid insomnia, and other conditions that impact adherence.
Metabolic Determinants of Cardiomyocyte Proliferation
Authors: Mohamed Tamer M A , Abouleisa Riham , Hill Bradford G
Published: March 2022

The adult mammalian heart is recalcitrant to regeneration after injury, in part due to the postmitotic nature of cardiomyocytes. Accumulating evidence suggests that cardiomyocyte proliferation in fetal or neonatal mammals and in regenerative non-mammalian models depends on a conducive metabolic state. Results from numerous studies in adult hearts indicate that conditions of relatively low fatty acid oxidation, low reactive oxygen species generation, and high glycolysis are required for induction of cardiomyocyte proliferation. Glycolysis appears particularly important because it provides branchpoint metabolites for several biosynthetic pathways that are essential for synthesis of nucleotides and nucleotide sugars, amino acids, and glycerophospholipids, all of which are required for daughter cell formation. In addition, the proliferative cardiomyocyte phenotype is supported in part by relatively low oxygen tensions and through the actions of critical transcription factors, coactivators, and signaling pathways that promote a more glycolytic and proliferative cardiomyocyte phenotype, such as hypoxia inducible factor 1α (Hif1α), Yes-associated protein (Yap), and ErbB2. Interventions that inhibit glycolysis or its integrated biosynthetic pathways almost universally impair cardiomyocyte proliferative capacity. Furthermore, metabolic enzymes that augment biosynthetic capacity such as phosphoenolpyruvate carboxykinase 2 and pyruvate kinase M2 appear to be amplifiers of cardiomyocyte proliferation. Collectively, these studies suggest that acquisition of a glycolytic and biosynthetic metabolic phenotype is a sine qua non of cardiomyocyte proliferation. Further knowledge of the regulatory mechanisms that control substrate partitioning to coordinate biosynthesis with energy provision could be leveraged to prompt or augment cardiomyocyte division and to promote cardiac repair.
The rise and spread of the SARS-CoV-2 AY.122 lineage in Russia
Authors: Klink Galya V , Safina Ksenia R , Nabieva Elena , Shvyrev Nikita , Garushyants Sofya , Alekseeva Evgeniia , Komissarov Andrey B , Danilenko Daria M , Pochtovyi Andrei A , Divisenko Elizaveta V , Vasilchenko Lyudmila A , Shidlovskaya Elena V , Kuznetsova Nadezhda A ,   The Coronavirus Russian Genetics Initiative (CoRGI) Consortium, Speranskaya Anna S , Samoilov Andrei E , Neverov Alexey D , Popova Anfisa V , Fedonin Gennady G ,   The CRIE Consortium, Akimkin Vasiliy G , Lioznov Dmitry , Gushchin Vladimir A , Shchur Vladimir , Bazykin Georgii A
Published: March 2022

Delta has outcompeted most preexisting variants of SARS-CoV-2, becoming the globally predominant lineage by mid-2021. Its subsequent evolution has led to the emergence of multiple sublineages, most of which are well-mixed between countries. By contrast, here we show that nearly the entire Delta epidemic in Russia has probably descended from a single import event, or from multiple closely timed imports from a single poorly sampled geographic location. Indeed, over 90 per cent of Delta samples in Russia are characterized by the nsp2:K81N + ORF7a:P45L pair of mutations which is rare outside Russia, putting them in the AY.122 sublineage. The AY.122 lineage was frequent in Russia among Delta samples from the start, and has not increased in frequency in other countries where it has been observed, suggesting that its high prevalence in Russia has probably resulted from a random founder effect rather than a transmission advantage. The apartness of the genetic composition of the Delta epidemic in Russia makes Russia somewhat unusual, although not exceptional, among other countries.
Visual Perception of 3D Space and Shape in Time - Part I: 2D Space Perception by 2D Linear Translation
Authors: Afifa Umaima , Carmona Javier , Dinh Amy , Espino Diego , McCarthy Trevor , Ta Brian , Wilson Patrick , Asdell Benjamin , Baik Jinwoo , Biju Archana , Chung Sonia , Dao Christopher , Diamond Mark , Doust Saba , East Angela , Espino Diego , Fleiszig-Evans Kailey , Franco Adrian , Garibay-Gutierrez Anthony , Guha Aparajeeta , Gunturu Roshan , Handley Luke , Honore Christina , Kannan Abinav , Khoo Jared , Khosla Mira , Kittur Chandan , Kwon Alexandra , Lee Jessica , Lwe Nicholas , Mayer Mylan , Mills Elizabeth , Pineda Delilah , Pourebrahim Pasha , Rajacich Jacob , Rizvi Shan , Rosales Liliana , Schummer Leonard , Sefkow Conor , Stangel Alexander , Ta Cindy , Ta Ivy , Tong Natalie , Tsujimoto Kyle , Vu Alyssa , Wang Henry , Yares Amanda , Yamaguchi Natsuko , Yoon Ki Woong , Yu Shuyi , Blaisdell Aaron P. , Arisaka Katsushi
Published: March 2022

Visual perception plays a critical role in navigating space and extracting useful semantic information crucial to survival. To identify distant landmarks, we constantly shift gaze vectors through saccades, while still maintaining the visual perception of stable allocentric space. How can we sustain stable allocentric space so effortlessly? To solve this question, we have developed a new concept of NHT (Neural Holography Tomography). This model states that retinotopy is invisible (not available to consciousness) and must be converted to a time code by traveling alpha brainwaves to perceive objects consciously. According to this framework, if identical alpha phases are continually assigned to a landmark, we perceive its exact and consistent allocentric location.

To test this hypothesis, we designed reaction time (RT) experiments to observe evidence of the predicted space-to-time conversion. Various visual stimuli were generated at a wide range of eccentricities either on a large TV (up to 40°) or by LED strips on a hemispherical dome (up to 60°). Participants were instructed to report the observed patterns promptly under either covert (no eye movement) or overt (with eye movement) conditions. As predicted, stimuli presented at the center of fixation always produced the fastest RTs. The additional RT delay was precisely proportional to the eccentricity of the peripheral stimulus presentation. Furthermore, both covert and overt attention protocols created the same RT delays, and trajectories of saccadic eye motions were in parallel to the overt RT vs. eccentricity. These findings strongly support our NHT model, in which the observed RT-eccentricity dependence is indicative of the spatiotemporal conversion required for maintaining a stable allocentric frame of reference. That is, we perceive space by time.
Laboratory verification of new commercial lateral flow assays for Cryptococcal antigen (CrAg) detection against the predicate IMMY LFA in a reference laboratory in South Africa
Authors: Coetzee Lindi-Marie , Glencross Deborah Kim
Published: March 2022

Background

Reflex Cryptococcal antigen (CrAg) testing in HIV-positive patients is done routinely at 47 laboratories in South Africa on samples with a confirmed CD4 count <100 cells/μl, using the IMMY Lateral Flow Assay (LFA) as the standardized predicate method.

Objective

This study aimed to verify the diagnostic performance of newer CrAg LFA assays against the predicate method.

Methods

Remnant CD4 samples collected between February and June 2019, with confirmed predicate LFA CrAg results, were retested on settled plasma with the (i) IMMY CrAg semi-quantitative (SQ) LFA; (ii) Bio-Rad RDT CryptoPS SQ; and (iii) Dynamiker CrAg SQ assays, within 24 hours of predicate testing. Sensitivity/ specificity analyses were conducted comparing predicate versus the newer assays, with McNemar’s test’s p-values reported for comparative results (p values <0.05 significant). Positivity grading was noted for the IMMY SQ and Bio-Rad assays.

Results

Of the 254 samples tested, 228 had comparative CrAg results across all assays. The predicate method reported 85 CrAg positive (37.2%), compared to between 35.08 and 37.28% for the Bio-Rad, IMMY SQ and Dynamiker assays. The IMMY CrAg SQ grading (+1 to +5) showed 67% of CrAg positive results had a grading ≥3, indicative of higher CrAg concentration (infection severity). False-negative results across all assays were <2%, with sensitivity >95% for all. False-positive results were highest for the Dynamiker LFA (14%) with a specificity of 77% (p=0.001). IMMY SQ and Bio-Rad assays specificities exceeded 90% (p=0.6 and 0.12). Internal quality control showed 100% accuracy for all assays.

Conclusion

Performance verification of newer CrAg LFA assays under typical laboratory conditions varied, with best results by IMMY SQ and Bio-Rad. The high burden of HIV and cryptococcal disease in South Africa requires high specificity and - sensitivity (>90%) to prevent unnecessary treatment/hospitalization. The added value of positivity grading for patient management needs confirmation.
Molecular mechanisms of long-term light adaptation of an extremophilic alga Cyanidioschyzon merolae
Authors: Abram Mateusz , Kaňa Radek , Olofsson Didrik , Pniewski Filip , Šedivá Barbora , Stark Martha , Fossl Dylan , Slat Viktor , Neumann Alexander , Rader Stephen , Kargul Joanna
Published: March 2022

Oxygenic phototrophs have evolved a remarkable plethora of strategies to react to changes in light intensity and spectral range, which allows them to thrive in a wide range of environmental conditions. Varying light quality and quantity influences the balance between solar energy capture and utilisation in photosynthesis, affecting concomitantly the downstream processes of central carbon and nitrogen metabolism as well as cellular growth and division. Here, we performed a comprehensive analysis of the mechanisms of long-term photoacclimation of an extremophilic red alga Cyanidioschyzon merolae that grows in sulphuric hot springs at high temperatures and low pH. By using spectroscopic, confocal fluorescence microscopy, photosynthetic performance measurements and global transcriptome analyses, we identified several molecular mechanisms underlying the long-term adaptation of this acido-thermophilic red alga to varying light intensity and spectral quality. These include: (1) remodelling of the functional antenna size of both photosystems; (2) rearrangement of the PSB/PSII/PSI microdomains within thylakoids; (3) modulation of the photosynthetic performance parameters, especially at the level of non-photochemical quenching, and (4) transcriptional regulation of photosynthesis and its regulatory components as well as downstream metabolic pathways related to ROS detoxification, cell/organelle division, and central carbon and nitrogen metabolism. Such an intricate network of interplay between light-driven reactions and downstream metabolic pathways provides the necessary basis for maintaining the highest photosynthetic performance under light-limiting conditions.
Computational Assessment of Different Structural Models for Claudin-5 Complexes in Blood-Brain-Barrier Tight-Junctions
Authors: Berselli Alessandro , Alberini Giulio , Benfenati Fabio , Maragliano Luca
Published: March 2022

The blood-brain barrier (BBB) strictly regulates the exchange of ions and molecules between the blood and the central nervous system. Tight junctions (TJs) are multimeric structures that control the transport through the paracellular spaces between adjacent brain endothelial cells of the BBB. Claudin-5 (Cldn5) proteins are essential for the TJ formation and assemble into multi-protein complexes via cis-interactions within the same cell membrane and trans-interactions across two contiguous cells. Despite the relevant biological function of Cldn5 proteins and their role as targets of brain drug delivery strategies, the molecular details of their assembly within TJs are still unclear. Two different structural models have been recently introduced, in which Cldn5 dimers belonging to opposite cells join to generate paracellular pores. However, a comparison of these models in terms of ionic transport features is still lacking. In this work, we used molecular dynamics simulations and free energy (FE) calculations to assess the two Cldn5 pore models and investigate the thermodynamic properties of water and physiological ions permeating through them. Despite different FE profiles, both structures present single/multiple FE barriers to ionic permeation, while being permissive to water flux. These results reveal that both models are compatible with the physiological role of Cldn5 TJ strands. By identifying the protein-protein surface at the core of TJ Cldn5 assemblies, our computational investigation provides a basis for the rational design of synthetic peptides and other molecules capable of opening paracellular pores in the BBB.
Tyrosine phosphorylation tunes chemical and thermal sensitivity of TRPV2 ion channel
Authors: Mo Xiaoyi , Pang Peiyuan , Wang Yulin , Jiang Dexiang , Zhang Mengyu , Li Yang , Wang Peiyu , Geng Qizhi , Xie Chang , Du Hai-Ning , Zhong Bo , Li Dongdong , Yao Jing
Published: March 2022

Transient receptor potential vanilloid 2 (TRPV2) is a multimodal ion channel widely regulating central and peripheral functions. Its important involvement in immune responses has been suggested such as in the macrophages’ phagocytosis process. However, the endogenous signaling cascades controlling the gating of TRPV2 remain to be understood. Here, we report that enhancing tyrosine phosphorylation remarkably alters the chemical and thermal sensitivities of TRPV2 endogenously expressed in rat bone marrow-derived macrophages. We identify that the protein tyrosine kinase JAK1 mediates TRPV2 phosphorylation at the molecular sites Tyr(335), Tyr(471), and Tyr(525). JAK1 phosphorylation is required for maintaining TRPV2 activity and the phagocytic ability of macrophages. We further show that TRPV2 phosphorylation is dynamically balanced by protein tyrosine phosphatase non-receptor type 1 (PTPN1). PTPN1 inhibition increases TRPV2 phosphorylation, further reducing the activation temperature threshold to ∼40 °C. Our data thus unveil an intrinsic mechanism where the phosphorylation/dephosphorylation dynamic balance sets the basal chemical and thermal sensitivity of TRPV2. Targeting this pathway will aid therapeutic interventions in physiopathological contexts.
Effects of dopamine D2 and opioid receptor antagonism on the trade-off between model-based and model-free behavior in healthy volunteers
Authors: Mikus Nace , Korb Sebastian , Massaccesi Claudia , Gausterer Christian , Graf Irene , Willeit Matthäus , Eisenegger Christoph , Lamm Claus , Silani Giorgia , Mathys Chris
Published: March 2022

Our daily behaviour requires a flexible arbitration between actions we do out of habit and actions that are directed towards a specific goal. Drugs that target opioid and dopamine receptors are notorious for inducing maladaptive habitual drug consumption, yet how the opioidergic and dopaminergic neurotransmitter systems contribute to the arbitration between habitual and goal-directed behaviour is poorly understood. By combining pharmacological challenges with a well-established decision-making task and a novel computational model, we show that the administration of the D2 dopamine receptor antagonist amisulpride led to an increase in goal-directed or ‘model-based’ relative to habitual or ‘model-free’ behaviour, whereas the non-selective opioid receptor antagonist naltrexone had no appreciable effect. These findings highlight the distinct functional contributions of dopamine and opioid receptors to goal-directed and habitual behaviour and support the notion that D2 receptor antagonists promote stabilisation of goal-relevant information.
Myo1e knockout in the adult podocytes leads to proteinuria but has less severe consequences for kidney function than Myo1e loss during renal development
Authors: Chase Sharon E. , Krendel Mira
Published: March 2022

Myosin 1e (Myo1e) is expressed in specialized epithelial cells in the kidney (podocytes) and plays an important role in renal filtration. Knockout of Myo1e in mice and mutations in the MYO1E gene in humans cause proteinuria and disrupt the ultrastructure of glomeruli, the initial segments of renal nephrons that are responsible for selective excretion of waste products without the loss of proteins from the bloodstream. Previous studies have demonstrated that the loss of Myo1e early in development results in severe defects in renal function in mice and may lead to end-stage renal disease in patients homozygous for MYO1E mutations. However, little is known about the effects of Myo1e loss later in life. In this study, we used inducible knockout of Myo1e in mouse podocytes to examine the effects of Myo1e loss from the adult kidneys. We have found that Myo1e loss after the completion of renal development causes proteinuria and podocyte defects but the effects are milder and more variable compared to the effects of Myo1e knockout in developing podocytes. These findings indicate that Myo1e plays an important role in podocyte development and differentiation but may also contribute to the maintenance of the glomerular barrier in the adult kidneys.
Diversity in DNA sequence, structure, and heterozygosity of nuclear rRNA gene region in Neopyropia yezoensis
Authors: Mizutani Yukino , Nagano Yukio , Kimura Kei , Kobayashi Genta , Kawamura Yoshio
Published: March 2022

DNA sequence reads of Neopyropia yezoensis (susabi-nori), its relative N. tenera (asakusa-nori), and their hybrids available in the sequence read archive produced assembled sequences of the nuclear rRNA gene region for 82 samples. Analysis of the assembled sequences revealed structural differences in the region of nuclear rRNA genes, with 17 forms depending on the presence or absence of introns and their lengths. The samples were divided into three groups based on differences in DNA sequences: Japanese N. yezoensis, Chinese N. yezoensis, and N. tenera/hybrids of N. tenera and N. yezoensis that exist in both countries. Despite genetic differentiation, the Japanese and Chinese N. yezoensis exhibit common structural forms. One sample of Chinese N. yezoensis presented almost 1:1 heterozygosity, whereas five other samples of Chinese N. yezoensis showed non-1:1 heterozygosity. In the latter case, neither the ratio of alleles nor the ratio of the number of introns was 1:1, suggesting the existence of an ongoing mechanism to eliminate the nuclear rRNA gene region on one of the homologous chromosomes in N. yezoensis.
Dynamic causal modelling shows a prominent role of local inhibition in alpha power modulation in higher visual cortex
Authors: Van de Steen Frederik , Pinotsis Dimitris , Devos Wouter , Colenbier Nigel , Bassez Iege , Friston Karl , Marinazzo Daniele
Published: March 2022

During resting-state EEG recordings, alpha activity is more prominent over the posterior cortex in eyes-closed (EC) conditions compared to eyes-open (EO). In this study, we characterized the difference in spectra between EO and EC conditions using dynamic causal modelling. Specifically, we investigated the role of intrinsic and extrinsic connectivity—within the visual cortex—in generating EC-EO alpha power differences over posterior electrodes. The primary visual cortex (V1) and the bilateral middle temporal visual areas (V5) were equipped with bidirectional extrinsic connections using a canonical microcircuit. The states of four intrinsically coupled subpopulations—within each occipital source—were also modelled. Using Bayesian model selection, we tested whether modulations of the intrinsic connections in V1, V5 or extrinsic connections (or a combination thereof) provided the best evidence for the data. In addition, using parametric empirical Bayes (PEB), we estimated group averages under the winning model. Bayesian model selection showed that the winning model contained both extrinsic connectivity modulations, as well as intrinsic connectivity modulations in all sources. The PEB analysis revealed increased extrinsic connectivity during EC. Overall, we found a reduction in the inhibitory intrinsic connections during EC. The results suggest that the intrinsic modulations in V5 played the most important role in producing EC-EO alpha differences, suggesting an intrinsic disinhibition in higher order visual cortex, during EC resting state.

Author summary

One of the strongest signals that can be measured using EEG are so called alpha rhythms. These are neural oscillations that fall within the 8-12Hz frequency range. Alpha rhythms are most prominent when the eyes are closed and are seen at the electrodes placed at the back of the head. In this study, we studied the mechanism of alpha rhythms changes when going from eyes-open to an eyes-closed state. We used a biologically plausible model including different neural populations. We focused on modelling connections within and between different neural sources of the visual cortex and how they are modulated when going from eyes-open to an eyes closed state. We found evidence that inhibitory neurons play an important role in alpha rhythms.
The innovation of the symbiosome has enhanced the evolutionary stability of nitrogen fixation in legumes
Authors: de Faria Sergio M. , Ringelberg Jens J. , Gross Eduardo , Koenen Erik J.M. , Cardoso Domingos , Ametsitsi George K.D. , Akomatey John , Maluk Marta , Tak Nisha , Gehlot Hukam S. , Wright Kathryn M. , Teaumroong Neung , Songwattana Pongpan , de Lima Haroldo C. , Prin Yves , Zartmann Charles , Sprent Janet I. , Ardley Julie , Hughes Colin E. , James Euan K.
Published: March 2022

Nitrogen-fixing symbiosis is globally important in ecosystem functioning and agriculture, yet the evolutionary history of nodulation remains the focus of considerable debate. Recent evidence suggesting a single origin of nodulation followed by massive parallel evolutionary losses raises questions about why a few lineages in the N2-fixing clade retained nodulation and diversified as stable nodulators while most did not. Within legumes, nodulation is restricted to the two most diverse subfamilies, Papilionoideae and Caesalpinioideae, which show stable retention of nodulation across their core clades.

We characterize two nodule anatomy types across 128 species in 56 of the 150 genera of the legume subfamily Caesalpinioideae: 1) fixation thread nodules (FTs), where nitrogen-fixing bacteroids are retained within the apoplast in modified infection threads and 2) symbiosomes, where rhizobia are symplastically internalized in the host cell cytoplasm within membrane-bound symbiosomes.

Using a robust phylogenomic tree based on 997 genes from 146 caesalpinioid genera, we show that losses of nodulation are more prevalent in lineages with FTs.

We propose that evolution of the symbiosome allows for a more intimate and enduring symbiosis through greater compartmentalisation of their rhizobial microsymbionts, resulting in greater evolutionary stability of nodulation across this species-rich pantropical clade of legumes.
Elaboration of a MALDI-TOF Mass Spectrometry-based Assay of Parkin Activity and High-Throughput screening platform for Parkin Activators
Authors: Traynor Ryan , Moran Jennifer , Stevens Michael , Knebel Axel , Behrouz Bahareh , Merchant Kalpana , Hastie C. James , Davies Paul , Muqit Miratul M. K. , De Cesare Virginia
Published: March 2022

Parkinson’s disease (PD) is a progressive neurological disorder that manifests clinically as alterations in movement (bradykinesia, postural instability, loss of balance, and resting tremors) as well as multiple non-motor symptoms including but not limited to cognitive and autonomic abnormalities. Mitochondrial dysfunction has been linked to sporadic PD and loss-of-function mutations in genes encoding the ubiquitin E3 ligase Parkin and protein kinase, PTEN-induced kinase 1 (PINK1), that regulate mitophagy, are causal for familial and juvenile PD1-3. Among several therapeutic approaches being explored to treat or improve PD patient’s prognosis, the use of small molecules able to reinstate or boost Parkin activity represents a potential pharmacological treatment strategy4. A major barrier is the lack of high throughput platforms based on robust and accurate quantification of Parkin activity in vitro. Here we present two different and complementary Matrix Assisted Laser Desorption/Ionization-Time of Flight mass spectrometry (MALDI-TOF MS) based approaches for the quantification of Parkin E3 ligase activity in vitro. These methods recapitulate distinct aspects of ubiquitin conjugation: Parkin auto-ubiquitylation and Parkin-catalysed discharge on lysine residues. Both approaches are scalable for high-throughput primary screening to facilitate the identification of Parkin modulators.
Alternative 3′ UTRs contributes to post-transcriptional gene expression regulation under high salt stress
Authors: Wang Taotao , Ye Wenbin , Zhang Jiaxiang , Li Han , Zeng Weike , Zhu Sheng , Ji Guoli , Wu Xiaohui , Ma Liuyin
Published: March 2022

High salt stress continually challenges growth and survival of many plants, but the underlying molecular basis is not fully explored. Alternative polyadenylation (APA) produces mRNAs with different 3′UTRs (alternative 3′UTRs) to regulate gene expression at post-transcriptional level. However, the roles of such process in response to salt stress remain elusive. Here, we reported that alternative 3′UTRs responded to high salt stress in the halophyte-Spartina alterniflora, which tolerant to hash salt environment. High salt stress induced the global APA and increased the prevalence of APA events. Strikingly, high salt stress significantly led to 3′ UTR lengthening of 207 transcripts through increasing the usage of distal poly(A) sites. Transcripts with alternative 3′ UTRs were mainly enriched in salt stress related ion transporters. Alternative 3′ UTRs of SaHKT1 increased RNA stability and protein synthesis in vivo. Regulatory AU-rich elements were identified in the alternative 3′ UTRs and alternative 3′ UTRs increased protein level of SaHKT1 in an AU-rich element dependent manner. Finally, 3′ UTR lengthening might result from variations in poly(A) signals and poly(A) factors. Overall, these results suggest that APA is a potential novel high salt stress responsive mechanism by modulating mRNA 3′ UTR length. These results also reveal complex regulator roles of alternative 3′ UTRs coupling alternative polyadenylation and regulatory elements at post-transcriptional level in plants.

One sentence summary

Alternative 3′ UTRs acts as a potential novel mechanism in gene expression regulation of high salt tolerant genes
Connecting the Dots: PHF13 and cohesin promote polymer-polymer phase separation of chromatin into chromosomes
Authors: Rossi Francesca , Buschow Rene , Glaser Laura V. , Schubert Tobias , Staege Hannah , Grimme Astrid , Will Hans , Milke Thorsten , Vingron Martin , Chiariello Andrea M. , Kinkley Sarah
Published: March 2022

How interphase chromatin compacts into mitotic chromosomes has eluded researchers for over a century. Here we show that PHF13, a tightly regulated H3K4me epigenetic reader, and cohesin, a mediator of chromatin architecture, cooperate to drive polymer-polymer-phase-separation (PPPS) and higher order compaction of chromatin into chromosomes. PHF13 interacts with cohesin, shows similar dynamics during mitosis, and their co-depletion dramatically impairs mitotic condensation. Mechanistically, we demonstrate that PHF13 stabilizes cohesin chromatin interactions and that itself oligomerizes, resulting in a polymer with increased chromatin avidity and the ability to bridge neighboring and distant nucleosomes. Consistently, molecular dynamic simulations modelling the ability of PHF13 and cohesin to drive chromatin phase separations recapitulated our in vivo observations and are in line with 2-step condensation models.
The evolution of ageing in cooperative breeders
Authors: Kreider Jan J. , Kramer Boris H. , Komdeur Jan , Pen Ido
Published: March 2022

Cooperatively breeding animals live longer than their solitary counterparts. The traditional explanation for this is that cooperative breeding evolves more readily in long-lived species. Here, we reverse this argument and show that long lifespans are an evolutionary consequence of cooperative breeding. Natural selection favours a delayed onset of senescence in cooperative breeders, relative to solitary breeders, because cooperative breeders have a delayed age of first reproduction due to reproductive queueing. Especially long lifespans evolve in cooperative breeders with age-dependent reproductive queueing. Finally, we show that lower genetic relatedness among group members leads to the evolution of longer lifespans. This is because selection against higher mortality is weaker when mortality reduces competition between relatives. Our results link the evolutionary theory of ageing with kin selection theory, demonstrating that the evolution of ageing in cooperative breeders is driven by the timing of reproduction and kin structure within breeding territories.