bluuebunny/crossref_metadata_2025 huggingface dataset:
Costly Miscommunication: College Students with Disabilities’ Perceptions of COVID-19 Vaccine Costs
Authors: Taylor Z.W. , Charran Chelseaia
Published: November 2021

Institutions of higher education have mandated COVID-19 vaccinations for students wishing to return to an on-campus, in-person learning experience. However, college students with disabilities (SWDs) may be hesitant to take a COVID-19 vaccine for a variety of reasons, possibly delaying or denying these students’ access to higher education. Yet, an under-researched aspect of COVID-19 vaccinations and related communication is whether college students with disabilities understand that the COVID-19 vaccine is free and whether that understanding varies by intersectional identities. As a result, this study’s research team surveyed 245 college students with disabilities to explore these students’ knowledge of vaccine costs and whether differences exist between groups. Data suggests many college students with disabilities do not know that COVID-19 vaccinations are free: White/Caucasian SWDs were most aware of COVID-19 vaccines being free (23.6%), while Latinx students were least aware (1.3%). Moreover, women were more aware of free COVID-19 vaccines (14.8%) than men (11.4%), first generation college students were more aware (15.6%) than non-first generation college students (12.2%), and full-time students (19%) were more aware than part-time students (8.9%). Overall, less than 25% of SWDs understood that COVID-19 vaccines are free. Implications for health communication, vaccine awareness, and higher education policy are addressed.
Evaluation of a Machine Learning Approach Utilizing Wearable Data for Prediction of SARS-CoV-2 Infection in Healthcare Workers
Authors: Hirten Robert P. , Tomalin Lewis , Danieletto Matteo , Golden Eddye , Zweig Micol , Kaur Sparshdeep , Helmus Drew , Biello Anthony , Pyzik Renata , Bottinger Erwin P , Keefer Laurie , Charney Dennis , Nadkarni Girish N. , Suarez-Farinas Mayte , Fayad Zahi A.
Published: November 2021

Importance

Passive and non-invasive identification of SARS-CoV-2 infection remains a challenge. Widespread use of wearable devices represents an opportunity to leverage physiological metrics and fill this knowledge gap.

Objective

To determine whether a machine learning model can detect SARS-CoV-2 infection from physiological metrics collected from wearable devices.

Design

A multicenter observational study enrolling health care workers with remote follow-up.

Setting

Seven hospitals from the Mount Sinai Health System in New York City

Participants

Eligibility criteria included health care workers who were ≥18 years, employees of one of the participating hospitals, with at least an iPhone series 6, and willing to wear an Apple Watch Series 4 or higher. We excluded participants with underlying autoimmune/inflammatory diseases, and medications known to interfere with autonomic function. We enrolled participants between April 29th, 2020, and March 2nd, 2021, and followed them for a median of 73 days (range, 3-253 days). Participants provided patient-reported outcome measures through a custom smartphone application and wore an Apple Watch, collecting heart rate variability and heart rate data, throughout the follow-up period.

Exposure

Participants were exposed to SARS-CoV-2 infection over time due to ongoing community spread.

Main Outcome and Measure

The primary outcome was SARS-CoV-2 infection, defined as ±7 days from a self-reported positive SARS-CoV-2 nasal PCR test.

Results

We enrolled 407 participants with 49 (12%) having a positive SARS-CoV-2 test during follow-up. We examined five machine-learning approaches and found that gradient-boosting machines (GBM) had the most favorable 10-CV performance. Across all testing sets, our GBM model predicted SARS-CoV-2 infection with an average area under the receiver operating characteristic (auROC)=85% (Confidence Interval 83-88%). The model was calibrated to improve sensitivity over specificity, achieving an average sensitivity of 76% (CI ±∼4%) and specificity of 84% (CI ±∼0.4%). The most important predictors included parameters describing the circadian HRV mean (MESOR) and peak-timing (acrophase), and age.

Conclusions and Relevance

We show that a tree-based ML algorithm applied to physiological metrics passively collected from a wearable device can identify and predict SARS-CoV2 infection. Utilizing physiological metrics from wearable devices may improve screening methods and infection tracking.
Inhaled Corticosteroids for Outpatients with Covid-19: A Meta-Analysis
Authors: Lee Todd C. , Bortolussi-Courval Émilie , Belga Sara , Daneman Nick , Chan Adrienne K. , Hanula Ryan , Ezer Nicole , McDonald Emily G.
Published: November 2021

The role of inhaled corticosteroids for outpatient COVID-19 is evolving. We meta-analyzed reported clinical trials and estimated probability of any effect and number needed to treat of 50 or 20 for symptom resolution by day 14 [100%, 99.8%, 93.1%] and hospitalization [89.3%, 72.9%, 26.7%] respectively.
Association of preference and frequency of teleworking with work functioning impairment: a nationwide cross-sectional study of Japanese full-time employees
Authors: Yamashita Satoshi , Ishimaru Tomohiro , Nagata Tomohisa , Tateishi Seiichiro , Hino Ayako , Tsuji Mayumi , Ikegami Kazunori , Muramatsu Keiji , Fujino Yoshihisa ,   the CORoNaWork Project
Published: November 2021

Objective

We examined whether teleworking preference and frequency were associated with work functioning impairment.

Methods

This online cross-sectional study was conducted using a self-administered questionnaire among 27,036 full-time Japanese workers. The Work Functioning Impairment Scale was used to measure work functioning impairment, and we performed multilevel logistic regression analysis.

Results

Higher odds ratios for work functioning impairment were observed among employees who preferred to telework compared with those who preferred working in the workplace. A similar trend was observed among employees who teleworked 4 or more days a week compared with those who almost never teleworked. When teleworking preference and frequency were adjusted, only teleworking preference was associated with work functioning impairment.

Conclusions

A preference for teleworking was associated with work functioning impairment and one factor that increased the teleworking frequency.
Cellular and humoral Immune response to mRNA COVID-19 vaccination in subjects with chronic lymphocytic leukemia
Authors: Lyski Zoe L. , Kim Myung S. , Xthona Lee David , Raué Hans-Peter , Raghunathan Vikram , Griffin Janet , Ryan Debbie , Brunton Amanda E. , Curlin Marcel E. , Slifka Mark K. , Messer William B. , Spurgeon Stephen E.
Published: November 2021

Chronic Lymphocytic Leukemia (CLL) is predominantly a B-lymphocyte leukemia associated with immune defects that are often exacerbated by CLL directed therapies. SARS-CoV-2 infection poses a significant risk of illness or mortality to CLL patients, and while SARS-CoV-2 vaccines are highly effective in immunocompetent individuals, efficacy varies substantially in immunocompromised patients, including those with CLL. To date, studies of COVID-19 vaccine immune responses in immunocompromised hosts have largely relied on semi-quantitative antibody titers that only partially characterize vaccine-elicited immune responses and do not measure B or T-cell specific responses that may also play a protective role in vaccinees. Here, we report RBD-specific antibody as well as B-cell and T-cell responses in an observational cohort of sixteen CLL subjects who received mRNA vaccination against SARS-CoV-2, finding a strong association between CLL treatment and vaccine immunogenicity, with important implications for vaccination timing in the context of CLL treatment or recovery from prior treatment.
HIV-specific CD8+ T-cells in tonsils express exhaustive TRM-like signatures
Authors: Fardoos Rabiah , Nyquist Sarah K. , Asowata Osaretin E. , Kazer Samuel W. , Singh Alveera , Ngoepe Abigail , Giandhari Janifer , Mthabela Ntombifuthi , Ramjit Dirhona , Singh Samita , Karim Farina , Buus Søren , Anderson Frank , Porterfield James Z. , Sibiya Andile L. , Bipath Rishan , Moodley Kumeshan , Kuhn Warren , Berger Bonnie , Nguyen Son , Oliveira Tulio de , Ndung’u Thumbi , Goulder Philip , Shalek Alex K. , Leslie Alasdair , Kløverpris Henrik N.
Published: November 2021

Lymphoid tissues are an important HIV reservoir site that persists in the face of antiretroviral therapy and natural immunity. Targeting these reservoirs by harnessing the antiviral activity of local tissue resident memory ( TRM) CD8+ T-cells is of great interest, but limited data exist on TRMs within lymph nodes of people living with HIV (PLWH). Here, we studied tonsil CD8+ T-cells obtained from PLWH and uninfected controls from South Africa. We show that these cells are preferentially located outside the germinal centers (GCs), the main reservoir site for HIV, and display a low cytolytic and transcriptionally TRM-like profile that is distinct from blood. In PLWH, CD8+ TRM-like cells are highly expanded and adopt a more cytolytic, activated and exhausted phenotype characterized by increased expression of CD69, PD-1 and perforin, but reduced CD127. This phenotype was enhanced in HIV-specific CD8+ T-cells from tonsils compared to matched blood. Single-cell profiling of these cells revealed a clear transcriptional signature of T-cell activation, clonal expansion and exhaustion ex-vivo. In contrast, this signature was absent from HIV-specific CD8+ T-cells in tonsils isolated from a natural HIV controller, who expressed lower levels of cell surface PD-1 and CXCR5, and reduced transcriptional evidence of T-cell activation, exhaustion and cytolytic activity. Thus, we show that HIV-specific TRM-like CD8+ T-cells in tonsils from non-HIV controllers are enriched for activation and exhaustion profiles compared to those in blood, suggesting that lymphoid HIV-specific CD8+ TRM cells are potentially ideal candidates for immunotherapy to modulate their ability to targeting the HIV reservoirs.
Dynamics of peripheral blood flow across sleep stages
Authors: Fan Zhiwei , Suzuki Yoko , Jiang Like , Okabe Satomi , Honda Shintaro , Endo Junki , Watanabe Takahiro , Abe Takashi
Published: November 2021

Study Objectives

Pulse rate variability (PRV) derived from peripheral blood flow has been reported as a surrogate parameter for heart rate variability (HRV). However, there are currently no studies reporting systematic comparisons of PRV with HRV in a normal sleep state. Whether PRV can provide similar information regarding sleep stages remains unclear. Peripheral blood flow may also be modulated differently across sleep stages. Thus, we aimed to investigate blood flow dynamics and compare PRV with HRV across sleep stages to see if blood flow can provide further information about sleep stages.

Methods

We performed electrocardiography and simultaneously measured blood flow from the right index finger and ear concha of 45 healthy participants (13 women; mean age, 22.5 ± 3.4 years) during one night of sleep. Time-domain, frequency-domain, and non-linear indices of PRV/HRV, and time- and frequencydomain blood flow parameters were calculated.

Results

Finger-PRV results showed similar patterns to HRV results for most parameters. Finger-blood flow parameters in the time and frequency domains also showed information about the different sleep stages. Further, both finger- and ear-blood flow results showed 0.2–0.3 Hz oscillations that varied with sleep stages, with a significant increase in N3, suggesting a modulation (of respiration) within this frequency band.

Conclusions

These results suggest that PRV can provide as much information as HRV for different sleep stages. Furthermore, the results show that blood flow + PRV could be more advantageous than HRV alone in the assessment of the sleep state and related autonomic nervous activity.

Statement of Significance

The research provides comprehensive information on peripheral blood flow (BF) activity across sleep stages for the first time, as the major novelty of our work. The second contribution is a systematic study comparing BF-derived pulse rate variability (PRV) with heart rate variability across sleep stages in a normal sleep state. We believe that our work makes a significant contribution to the literature because it provides comprehensive information on the potential of BF+PRV as a new biomarker for assessing the sleep state. Further, this study contributes to developing a more convenient method of assessing the sleep state in the clinical and home/work setting.
Spinal cord injury reprograms muscle fibro-adipogenic progenitors to form heterotopic bones within muscles
Authors: Tseng Hsu-Wen , Girard Dorothée , Alexander Kylie A. , Millard Susan M , Torossian Frédéric , Anginot Adrienne , Fleming Whitney , Gueguen Jules , Goriot Marie-Emmanuelle , Clay Denis , Jose Beulah , Nowlan Bianca , Pettit Allison R. , Salga Marjorie , Genêt François , Le Bousse-Kerdilès Marie-Caroline , Banzet Sébastien , Levesque Jean-Pierre
Published: November 2021

The cells-of-origin of neurogenic heterotopic ossifications (NHO), which develop frequently in the periarticular muscles following spinal cord injuries (SCI) and traumatic brain injuries, remain unclear because the skeletal muscle harbors two progenitor cell populations: satellite cells (SCs) which are myogenic, and fibro-adipogenic progenitors (FAPs) which are mesenchymal. Lineage-tracing experiments using the Cre recombinase /LoxP system were performed in two mouse strains with the fluorescent protein ZsGreen specifically expressed in either SCs or FAPs in the skeletal muscles under the control of the Pax7 or Prrx1 gene promotors respectively. These experiments demonstrate that following a muscle injury, SCI causes the upregulation of PDGFRα on FAPs but not SCs and the failure of SCs to regenerate myofibers in the injured muscle, with instead reduced apoptosis and continued proliferation of muscle resident FAPs enabling their osteogenic differentiation into NHO. No cells expressing ZsGreen under the Prrx1 promoter were detected in the blood after injury suggesting that the cells-of-origin of NHO are locally derived from the injured muscle. We validated these findings in the human pathology using human NHO biopsies. PDGFRα+ mesenchymal cells isolated from the muscle surrounding NHO biopsies could develop ectopic human bones when transplanted into immunocompromised mice whereas CD56+ myogenic cells had a much lower potential. Therefore, NHO is a pathology of the injured muscle in which SCI reprograms FAPs to uncontrolled proliferation and differentiation into osteoblasts.
Mapping single-cell transcriptomes to copy number evolutionary trees
Authors: Ferreira Pedro F. , Kuipers Jack , Beerenwinkel Niko
Published: November 2021

Cancer arises and evolves by the accumulation of somatic mutations that provide a selective advantage. The interplay of mutations and their functional consequences shape the evolutionary dynamics of tumors and contribute to different clinical outcomes. In the absence of scalable methods to jointly assay genomic and transcriptomic profiles of the same individual cell, the two data modalities are usually measured separately and need to be integrated computationally. Here, we introduce SCATrEx, a statistical model to map single-cell gene expression data onto the evolutionary history of copy number alterations of the tumor. SCATrEx jointly assigns cancer cells assayed with scRNA-seq to copy number profiles arranged in a copy number aberration tree and augments the tree with clone-specific clusters. Our simulations show that SCATrEx improves over both state-of-the-art unsupervised clustering methods and cell-to-clone assignment methods. In an application to real data, we observe that SCATrEx finds inter-clone and intra-clone gene expression heterogeneity not detectable using other integration methods. SCATrEx will allow for a better understanding of tumor evolution by jointly analysing the genomic and transcriptomic changes that drive it.
CDK1 and PLK1 cooperate to regulate BICD2, dynein activation and recruitment to the nucleus as well as centrosome separation in G2/M
Authors: Gallisà-Suñé Núria , Sànchez-Fernàndez-de-Landa Paula , Zimmermann Fabian , Serna Marina , Paz Joel , Regué Laura , Llorca Oscar , Lüders Jens , Roig Joan
Published: November 2021

The activity of dynein is regulated by a number of adaptors that mediate its interaction with dynactin, effectively activating the motor complex while also connecting it to different cargos. The regulation of adaptors is consequently central to dynein physiology, but remains largely unexplored. We now describe that one of the best-known dynein adaptors, BICD2, is effectively activated through phosphorylation. In G2 phosphorylation of BICD2 by CDK1 promotes its interaction with PLK1. In turn, PLK1 phosphorylation of a single residue in the N-terminus of BICD2 results in a conformational change that facilitates interaction with dynein and dynactin, allowing the formation of active motor complexes. BICD2 phosphorylation is central for dynein recruitment to the nuclear envelope, centrosome tethering to the nucleus and centrosome separation in G2/M. This work reveals adaptor activation through phosphorylation as crucial for the spatiotemporal regulation of dynein activity.
Genome-wide association study of cerebellar volume
Authors: Tissink E.P. , de Lange S.C. , Savage J.E. , Wightman D.P. , Kelly K.M. , Nagel M. , van den Heuvel M.P. , Posthuma D.
Published: November 2021

Cerebellar volume is highly heritable and associated with neurodevelopmental and neurodegenerative disorders. Understanding the genetic architecture of cerebellar volume may improve our insight into these disorders. This study aims to investigate the convergence of cerebellar volume genetic associations in close detail. A genome-wide associations study for cerebellar volume was performed in a sample of 27,486 individuals from UK Biobank, resulting in 29 genome-wide significant loci and a SNP heritability of 39.82%. We pinpoint variants that have effects on amino acid sequence or cerebellar gene-expression. Additionally, 85 genome-wide significant genes were detected and tested for convergence onto biological pathways, cerebellar cell types or developmental stages. Local genetic correlations between cerebellar volume and neurodevelopmental and neurodegenerative disorders reveal shared loci with Parkinson’s disease, Alzheimer’s disease and schizophrenia. These results provide insights into the heritable mechanisms that contribute to developing a brain structure important for cognitive functioning and mental health.
Pronounced uptake and metabolism of organic substrates by diatoms revealed by pulse-labeling metabolomics
Authors: Meyer Nils , Rydzyk Aljoscha , Pohnert Georg
Published: November 2021

Diatoms contribute as a dominant group of microalgae to approximately 20% of the global carbon fixation. In the plankton, these photosynthetic algae are exposed to a plethora of metabolites, especially when competing algae are lysed. It is well established that diatoms can take up specific metabolites, such as vitamins, amino acids as nitrogen source, or dimethylsulfoniopropoionate to compensate for changes in water salinity. It is, however, unclear to which extent diatoms take up other organic resources and if these are incorporated into the cell’s metabolism. Here, we ask about the general scope of uptake of metabolites from competitors. Using labeled metabolites released during lysis of algae grown under a 13CO2 atmosphere, we show that the cosmopolitan diatom Chaetoceros didymus takes up organic substrates with little bias and remarkable efficiency. The newly developed pulse label/ mass spectrometry metabolomics approach reveals that polarity and molecular weight has no detectable influence on uptake efficiency. We also reveal that the taken-up pool of metabolites is partly maintained unaltered within the cells but is also subject to catabolic and anabolic transformation. One of the most dominant phytoplankton groups is thus substantially competing with other heterotrophs for organic material, suggesting that the observed absorbotrophy may substantially impact organic material fluxes in the oceans. Our findings call for the refinement of our understanding of competition in the plankton.

Significance

This study demonstrates a remarkably universal uptake of organic substrates by diatoms. The extent to which one of the most dominant phytoplankton groups is competing for organic material in the plankton is documented by novel pulse labeling metabolomics studies. Our results show that uptake of organic material by the photosynthetic microalgae occurs with remarkably little bias. Taken-up metabolites are further transformed by the diatoms or directly incorporated into the algal metabolome. Our study calls for a re-consideration of organic material fluxes in the oceans. Also, our understanding of competition in the plankton will have to be refined. The broader implications for the cycling of resources in plankton communities are discussed within this work.
A lateral protrusion latticework connects neuroepithelial cells and is regulated during neurogenesis
Authors: Kasioulis Ioannis , Dady Alwyn , James John , Prescott Alan , Halley Pamela A. , Storey Kate G.
Published: November 2021

Dynamic contacts between cells within the developing neuroepithelium are poorly understood but play important roles in cell and tissue morphology and cell signalling. Here, using live-cell imaging and electron microscopy we reveal multiple protrusive structures in neuroepithelial apical endfeet of the chick embryonic spinal cord, including sub-apical protrusions that extend laterally within the tissue, and observe similar structures in human neuroepithelium. We characterise the dynamics, shape, and cytoskeleton of these lateral protrusions and distinguish these structures from cytonemes/filopodia and tunnelling nanotubes. We demonstrate that lateral protrusions form a latticework of membrane contacts between non-adjacent cells, depend on actin but not microtubule dynamics and provide a lamellipodial-like platform for further extending fine actin-dependent filipodia. We find that lateral protrusions depend on the actin-binding protein WAVE1: mutant-WAVE1 misexpression attenuated protrusion and generated a round-ended apical endfoot morphology. However, this did not alter apico-basal cell polarity nor reduce tissue integrity. During normal neuronal delamination sub-apical protrusions were withdrawn, but mutant-WAVE1-induced precocious protrusion loss was insufficient to trigger neurogenesis. This study uncovers a new form of cell-cell contact within the developing neuroepithelium regulation of which prefigures neuronal delamination.
Rapid ecological and evolutionary divergence during a poleward range expansion
Authors: Sheffer Monica M. , Schulze Brian , Zander Linda , Mouginot Pierick , Naef Thomas , Lalk Michael , Wurster Martina , Ahrend Clara , Kreyling Jürgen , Gillespie Rosemary G. , Hoff Katharina J. , Prost Stefan , Krehenwinkel Henrik , Uhl Gabriele
Published: November 2021

In response to climate change, a northward range expansion has been observed in many species. The wasp spider,Argiope bruennichi, has expanded from its historic range in the Mediterranean (“core”), now reaching as far as the Baltic States and Scandinavia (“edge”), even faster than the pace of climate change. We explored life history traits, adult phenotypes, offspring cold tolerance, and genomic patterns across the European range ofA. bruennichi, and found origin-, environment- and life stage-specific responses to the cold northern climate. Wasp spiders have shifted their phenology at the edge, with females maturing earlier and at a smaller size, but maintaining similar pigmentation, clutch sizes, and hatching success compared to the core region. Using a reciprocal common garden experiment on overwintering offspring from the core and edge, we found evidence for genetic adaptation and considerable phenotypic plasticity. Overwintering survival was lower under the cold winter treatment for spiderlings from both origins. However, the edge-origin spiderlings that survived the winter had lower lethal temperatures and enhanced supercooling ability with reduced phenotypic plasticity in supercooling points compared to core spiderlings, while the chill coma recovery time was similar. Metabolomic analysis revealed accumulations of amino acids and myo-inositol in the cold winter treatment, particularly in spiderlings from the edge population, suggesting a role of these metabolites in improving cold tolerance. Genotype-environment tests showed strong genetic association across the genome to seasonality and minimum winter temperature. The population genomic analysis across the European range splitsA. bruennichiinto two distinct genetic clusters through the center of Germany, which roughly aligns with turnover from an oceanic to continental climate zone, complementing the genotype-environment test results. Overall, our study highlights the importance of integrating data on phenological shifts, changes in life-history, and life stage-specific phenotypic plasticity and genetic adaptation to understand the impacts of range expansions and shifts. The nuanced processes of acclimation and adaptation we uncovered advocate for holistic investigations of evolutionary fitness and fitness-related traits in the context of organismal responses to novel and changing environments.
Microthrombocytopenia caused by impaired microtubule stability in RhoB-deficient mice
Authors: Englert Maximilian , Aurbach Katja , Gerber Annika , Heib Tobias , Becker Isabelle C. , Wackerbarth Lou M. , Kusch Charly , Baig Ayesha A. , Dütting Sebastian , Knaus Ulla G. , Stigloher Christian , Nieswandt Bernhard , Pleines Irina , Nagy Zoltan
Published: November 2021

Megakaryocytes are large cells in the bone marrow, which give rise to blood platelets. Platelet biogenesis involves megakaryocyte maturation, the localization of mature cells in close proximity to bone marrow sinusoids and the formation of protrusions, which are shed into the circulation. Rho GTPases play important roles in platelet biogenesis and function. RhoA-deficient mice display macrothrombocytopenia and a striking mislocalization of megakaryocytes into bone marrow sinusoids and a specific defect in G-protein signaling in platelets. However, the role of the closely related protein RhoB in megakaryocytes or platelets remains unknown. In this study, we show that, in contrast to RhoA deficiency, genetic ablation of RhoB in mice results in microthrombocytopenia (decreased platelet count and size). RhoB-deficient platelets displayed mild functional defects predominantly upon induction of the collagen/glycoprotein VI pathway. Megakaryocyte maturation and localization within the bone marrow, as well as actin dynamics were not affected in the absence of RhoB. However, in vitro generated proplatelets revealed pronouncedly impaired microtubule organization. Furthermore, RhoB-deficient platelets and megakaryocytes displayed selective defects in microtubule dynamics/stability, correlating with pronouncedly reduced levels of acetylated α-tubulin. Our findings imply that absence of this tubulin posttranslational modification results in decreased microtubule stability leading to microthrombocytopenia in RhoB-deficient mice. Our data thus points to specifically impaired microtubule - but not actin - dynamics as a general mechanism underlying the manifestation of microthrombocytopenia in vivo. We furthermore demonstrate that RhoA and RhoB have specific, non-redundant functions in the megakaryocyte lineage.

KEY POINTS

RhoB-deficient mice display microthrombocytopenia

RhoB has different functions in the megakaryocyte lineage than RhoA and regulates microtubule dynamics
Prolonged and extended impacts of SARS-CoV-2 on the olfactory neurocircuit
Authors: Kishimoto-Urata Megumi , Urata Shinji , Kagoya Ryoji , Imamura Fumiaki , Nagayama Shin , Reyna Rachel A. , Maruyama Junki , Yamasoba Tatsuya , Kondo Kenji , Hasegawa-Ishii Sanae , Paessler Slobodan
Published: November 2021

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.
Diverse pathogens activate the host RIDD pathway to subvert BLOS1-directed immune defense
Authors: Wells Kelsey , He Kai , Pandey Aseem , Cabello Ana , Zhang Dong-Mei , Yang Jing , Gomez Gabriel , Liu Yue , Chang Hao-Wu , Li Xue-Qing , Zhang Hao , da Costa Luciana Fachini , Metz Richard P. , Johnson Charles D. , Martin Cameron , Skrobarczyk Jill , Berghman Luc R. , Patrick Kristin , Leibowitz Julian , Rice-Ficht Allison , Sze Sing-Hoi , Qian Xiaoning , Qin Qing-Ming , Ficht Thomas A. , de Figueiredo Paul
Published: November 2021

The phagocytosis and destruction of pathogens in lysosomes constitute central elements of innate immune defense. Here, we show that Brucella, the causative agent of brucellosis, the most prevalent bacterial zoonosis globally, subverts this immune defense pathway by activating regulated IRE1α-dependent decay (RIDD) of mRNAs encoding BLOS1, a protein that promotes endosome-lysosome fusion. RIDD-deficient cells and mice harboring a RIDD-incompetent variant of IRE1α were resistant to infection. Non-functional Blos1 struggled to assemble the BLOC-1-related complex (BORC), resulting in differential recruitment of BORC-related lysosome trafficking components, perinuclear trafficking of Brucella-containing vacuoles (BCVs), and enhanced susceptibility to infection. The RIDD-resistant Blos1 variant maintains the integrity of BORC and a higher-level association of BORC-related components that promote centrifugal lysosome trafficking, resulting in enhanced BCV peripheral trafficking and lysosomal-destruction, and resistance to infection. These findings demonstrate that host RIDD activity on BLOS1 regulates Brucella intracellular parasitism by disrupting BORC-directed lysosomal trafficking. Notably, coronavirus MHV also subverted the RIDD-BLOS1 axis to promote intracellular replication. Our work therefore establishes BLOS1 as a novel immune defense factor whose activity is hijacked by diverse pathogens.
A Trypanosoma brucei orphan kinesin employs a convergent microtubule organization strategy to complete cytokinesis
Authors: Sladewski Thomas E. , Campbell Paul C. , Billington Neil , D’Ordine Alexandra , de Graffenried Christopher L.
Published: November 2021

Many single-celled eukaryotes have complex cell morphologies defined by cytoskeletal elements comprising microtubules arranged into higher-order structures. Trypanosoma brucei (T. brucei) cell polarity is mediated by a parallel array of microtubules that underlie the plasma membrane and define the auger-like shape of the parasite. The subpellicular array must be partitioned and segregated using a microtubule-based mechanism during cell division. We previously identified an orphan kinesin, KLIF, that localizes to the division plane and is essential for the completion of cytokinesis. To gain mechanistic insight into how this novel kinesin functions to complete cleavage furrow ingression, we characterized the biophysical properties of the KLIF motor domain in vitro. We found that KLIF is a non-processive dimeric kinesin that dynamically crosslinks microtubules. Microtubules crosslinked in an antiparallel orientation are translocated relative to one another by KLIF, while microtubules crosslinked parallel to one another remain static, resulting in the formation of organized parallel bundles. In addition, we found that KLIF stabilizes the alignment of microtubule plus ends. These features provide a mechanistic understanding for how KLIF functions to form a new pole of aligned microtubule plus ends that defines the shape of the new posterior, which is a unique requirement for the completion of cytokinesis in T. brucei.
The most widespread phage in animals: Genomics and taxonomic classification of Phage WO
Authors: Bordenstein Sarah R. , Bordenstein Seth R.
Published: November 2021

Wolbachia are the most common obligate, intracellular bacteria in animals. They exist worldwide in arthropod and nematode hosts in which they commonly act as reproductive parasites or mutualists, respectively. Bacteriophage WO, the largest of Wolbachia’s mobile elements, includes reproductive parasitism genes, serves as a hotspot for genetic divergence and genomic rearrangement of the bacterial chromosome, and uniquely encodes a Eukaryotic Association Module with eukaryotic-like genes and an ensemble of putative host interaction genes. Despite WO’s relevance to genome evolution, selfish genetics, and symbiotic applications, relatively little is known about its origin, host range, diversification, and taxonomic classification. Here we analyze the most comprehensive set of 150 Wolbachia and phage WO assemblies to provide a framework for discretely organizing and naming integrated phage WO genomes. We demonstrate that WO is principally in arthropod Wolbachia with relatives in diverse endosymbionts and metagenomes, organized into four variants related by gene synteny, often oriented opposite the origin of replication in the Wolbachia chromosome, and the large serine recombinase is an ideal typing tool to assign taxonomic classification of the four variants. We identify a novel, putative lytic cassette and WO’s association with a conserved eleven gene island, termed Undecim Cluster, that is enriched with virulence-like genes. Finally, we evaluate WO-like Islands in the Wolbachia genome and discuss a new model in which Octomom, a notable WO-like Island, arose from a split with WO. Together, these findings establish the first comprehensive Linnaean taxonomic classification of endosymbiont phages that includes distinguishable genera of phage WO, a family of non-Wolbachia phages from aquatic environments, and an order that captures the collective relatedness of these viruses.
Digital twin predicting diet response before and after long-term fasting
Authors: Silfvergren Oscar , Simonsson Christian , Ekstedt Mattias , Lundberg Peter , Gennemark Peter , Cedersund Gunnar
Published: November 2021

Today, there is great interest in diets proposing new combinations of macronutrient compositions and fasting schedules. Unfortunately, there is little consensus regarding the impact of these different diets, since available studies measure different sets of variables in different populations, thus only providing partial, non-connected insights. We lack an approach for integrating all such partial insights into a useful and interconnected big picture. Herein, we present such an integrating tool. The tool uses a novel mathematical model that describes mechanisms regulating diet-response and fasting metabolic fluxes, both for organ-organ crosstalk, and inside the liver. The tool can mechanistically explain and integrate data from several clinical studies, and correctly predict new independent data, including data from a new clinical study. Using this model, we can predict non-measured variables, e.g. hepatic glycogen and gluconeogenesis, and we can quantify personalized expected differences in outcome for any diet. This constitutes a new digital twin technology.
Correlative microscopy reveals the nanoscale morphology of E. coli-derived supported lipid bilayers
Authors: Bali Karan , Mohamed Zeinab , Pappa Anna-Maria , Daniel Susan , Kaminski Clemens F. , Owens Róisín M. , Mela Ioanna
Published: November 2021

Supported lipid bilayers (SLBs) made from reconstituted lipid vesicles are an important tool in molecular biology. A breakthrough in the field has come with the use of vesicles derived from cell membranes to form SLBs. These new supported bilayers, consisting both of natural and synthetic components, provide a physiologically relevant system on which to study protein-protein interactions as well as protein-ligand interactions and other lipid membrane properties. These complex bilayer systems hold promise but have not yet been fully characterised in terms of their composition, ratio of natural to synthetic component and membrane protein content. Here, we describe a method of correlative atomic force (AFM) with structured illumination microscopy (SIM) for the accurate mapping of complex lipid bilayers that consist of a synthetic fraction and a fraction of lipids derived from Escherichia coli outer membrane vesicles (OMVs). We exploit the enhanced resolution and molecular specificity that SIM can offer to identify areas of interest in these bilayers and the atomic scale resolution that the AFM provides to create detailed topography maps of the bilayers. We are thus able to understand the way in which the two different lipid fractions (natural and synthetic) mix within the bilayers, quantify the amount of bacterial membrane incorporated in the bilayer and directly visualise the interaction of these bilayers with bacteria-specific, membrane-binding proteins. Our work sets the foundation for accurately understanding the composition and properties of OMV-derived SLBs and establishes correlative AFM/ SIM as a method for characterising complex systems at the nanoscale.
The Human Eye Transcriptome Atlas: A Searchable Comparative Transcriptome Database for Healthy and Diseased Human Eye Tissue
Authors: Wolf Julian , Boneva Stefaniya , Schlecht Anja , Lapp Thabo , Auw-Haedrich Claudia , Lagrèze Wolf , Agostini Hansjürgen , Reinhard Thomas , Schlunck Günther , Lange Clemens
Published: November 2021

The applications of deep sequencing technologies in life science research and clinical diagnostics have increased rapidly over the last decade. Although fast algorithms for data processing exist, intuitive, portable solutions for data analysis are still rare. For this purpose, we developed a web-based transcriptome database, which provides a platform-independent, intuitive solution to easily explore and compare ocular gene expression of 100 diseased and healthy human tissue samples from 15 different tissue types collected at the Eye Center of the University of Freiburg. To ensure comparability of expression between different tissues, reads were normalized across all 100 samples. Differentially expressed genes were calculated between each tissue type to determine tissue-specific genes. Unsupervised analysis of all 100 samples revealed an accurate clustering according to different tissue types. Cluster analysis based on known cell type-specific marker genes allowed differentiation of respective tissues. Several tissue-specific marker genes were identified. These genes were involved in tissue- or disease-specific processes, such as myelination for the optic nerve, visual perception for retina, keratinocyte differentiation for conjunctival carcinoma, as well as endothelial cell migration for choroidal neovascularization membranes. The results are accessible at the Human Eye Transcriptome Atlas website at https://www.eye-transcriptome.com. In summary, this searchable transcriptome database enables easy exploration of ocular gene expression in healthy and diseased human ocular tissues without bioinformatics expertise. Thus, it provides rapid access to detailed insights into the molecular mechanisms of various ocular tissues and diseases, as well as the rapid retrieval of potential new diagnostic and therapeutic targets.
A multivariate view of cognitive performance reveals positive correlation in the Trinidadian Guppy (Poecilia reticulata)
Authors: Prentice Pamela M , Thorton Alex , Wilson Alastair J
Published: November 2021

Cognitive variation is common among-individuals and can be consistent across time and context. From an evolutionary perspective, among-individual variation is important as a pre-requisite for natural selection and adaptive evolution. Selection is widely hypothesized to favor high cognitive performance but directional selection should erode variation over time, how then is cognitive variation maintained? As selection does not act on traits in isolation, covariance among specific cognitive traits and/or other aspects of phenotype (e.g. personality) could result in fitness trade-offs that are important in shaping evolutionary dynamics. Here we test this using Trinidadian guppies (Poecilia reticulata), using a multivariate approach by characterising the correlation structure among task-specific cognitive performance measures and a personality trait. We estimate the among-individual correlation matrix (ID) in performance across three cognitive tasks; colour association learning task; motor learning task; reversal learning task, and the personality trait ‘boldness’ measured as emergence time from a shelter. We found no support for trade-offs among performance in these tasks. Nor do we find evidence of hypothesised speed-accuracy trade-offs within the association learning task. Rather we find strong positive correlation structure inID,with 57% of variation explained by the leading eigen vector. While noting that non-cognitive factors and assay composition may affect the structure ofID, we suggest our findings are consistent with theg-model of cognitive performance variation, in which a dominant axis of variation loads positively on all performance measures. Thus, we add to a growing body of support for general variation among individuals in animal cognitive ability.
No Correlation Between Pollen Fertility and Viability: Differential Measures of Male Gametophytic Fitness inCannabis sativaL.
Authors: Wizenberg Sydney B. , Dang Michelle , Campbell Lesley G.
Published: November 2021

Pollen grains are male gametophytes, an ephemeral haploid generation of plants, commonly engaging in competition for a limited supply of ovules. Since differential male fertility may influence the direction and pace of population evolution, the relative fitness of pollen is regularly estimated as either pollen viability, the proportion of pollen containing intact cytoplasm’s and regenerative nuclei, or pollen fertility, the frequency of pollen germinating under standardized conditions. Here, we estimated the relative fitness of pollen in a dioecious, wind-pollinated model system,Cannabis sativa, by characterizing pollen fertility and viability from multiple sires. Pollen fertility quickly declined within two weeks of anther dehiscence, and pollen stored under freezer conditions did not germinate regardless of storage time. In contrast, pollen viability declined slowly and persisted longer than the lifetime of a sporophyte plant under both room temperature and freezer conditions. Pollen samples that underwent both fertility and viability analysis displayed no significant correlation, implying researchers cannot predict pollen fertility from pollen viability, nor infer male gametophytic fitness from a single measure. Our work demonstrates two approaches to measure proxies of male fitness inC. sativa, and identifies new questions around what are valuable estimates of male fitness in plants.
Mapping the sex determination region in the Salix F1 hybrid common parent population confirms a ZW system in six diverse species
Authors: Wilkerson Dustin G. , Taskiran Bircan , Carlson Craig H. , Smart Lawrence B.
Published: November 2021

Within the genus Salix, there are approximately 350 species native primarily to the northern hemisphere and adapted to a wide range of habitats. This diversity can be exploited to mine novel alleles conferring variation important for production as a bioenergy crop, but also to identify evolutionarily important genes, such as those involved in sex determination. To leverage this diversity, we created a mapping population by crossing six Salix species (S. viminalis, S. suchowensis, S. integra, S. koriyanagi, S. udensis, and S. alberti) to common male and female S. purpurea parents. Each family was genotyped via genotyping-by-sequencing and assessed for kinship and population structure as well as the construction of 16 backcross linkage maps to be used as a genetic resource for breeding and selection. Analyses of population structure resolved both the parents and F1 progeny to their respective phylogenetic section and indicated that the S. alberti parent was misidentified and was most likely S. suchowensis. Sex determining regions were identified on Salix chromosome 15 in the female-informative maps for seven of the eight families indicating that these species share a common female heterogametic ZW sex system. The eighth family, S. integra × S. purpurea, was entirely female and had a truncated chromosome 15. Beyond sex determination, the Salix F1 hybrid common parent population (Salix F1 HCP) introduced here will be useful in characterizing genetic factors underlying complex traits, aid in marker-assisted selection, and support genome assemblies for this promising bioenergy crop.
Parental environmental effects are common and strong, but unpredictable, in Arabidopsis thaliana
Authors: Latzel Vít , Fischer Markus , Groot Maartje , Gutzat Ruben , Lampei Christian , Ouborg Joop , Parepa Madalin , Schmid Karl , Vergeer Philippine , Zhang Yuanye , Bossdorf Oliver
Published: November 2021

The phenotypes of plants can be influenced by the environmental conditions experienced by their parents. In some cases, such parental effects have been found to be adaptive, which has led to much speculation about their ecological and evolutionary significance. However, there is still much uncertainty about how common and how predictable parental environmental effects really are. We carried out a comprehensive test for parental effects of different environmental stresses in the model plant Arabidopsis thaliana. We subjected plants of three Arabidopsis genotypes to a broad range of biotic or abiotic stresses, or combinations thereof, and compared their offspring phenotypes in a common environment. The majority of environmental stresses (16 out of 24 stress treatments) caused significant parental effects, in particular on plant biomass and reproduction, with positive or negative effects ranging from −35% to +38% changes in offspring fitness. The expression of parental effects was strongly genotype-dependent, with some effects only present in some genotypes but absent, or even in the opposite direction, in others. Parental effects of multiple environmental stresses were often non-additive, and their effects can thus not be predicted from what we know about the effects of individual stresses. Intriguingly, the direction and magnitude of parental effects were unrelated to the direct effects on the parents: some stresses did not affect the parents but caused substantial effects on offspring, while for others the situation was reversed. In summary, parental environmental effects are common and often strong in A. thaliana, but they are genotype-dependent and difficult to predict.

Significance

Stress experienced by plants can alter the phenotypes of their offspring. To understand the ecological and evolutionary significance of such parental effects, we must know how common and how predictable they are. In a large experiment with Arabidopsis thaliana, we show that the majority of 24 environmental stresses cause significant, and often strong, positive or negative parental effects. However, we also find that parental effects are genotype-specific and unrelated to the direct effect of individual stresses, and that multiple stresses often act in non-additive ways across generations. Thus, parental effects appear to be common and strong, but difficult to predict. Our findings have important implications for the study of plant responses to environmental change, and the design of stress experiments.