bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory protein genes and microRNAs in response to selenium stimuli in Pueraria lobata (Willd.) Ohwi
Authors: Li Yanni , He Meijun , Li Jishuang , Yao Yiwei , Zhu Li , Wu Bin
Published: December 2020

Regulatory protein genes and microRNAs (miRNAs) play important roles in response to abiotic and biotic stress, and the biosynthesis of secondary metabolites in plants. However, their responses to selenium (Se) stimuli have not been comprehensively studied in Pueraria lobata (Willd.) Ohwi, a selenocompound-rich medicinal and edible plant. In this study, we identified a total of 436/556/1161/624 transcription factors, 134/157/308/172 transcriptional regulators, and 341/456/250/518 protein kinases, which were co-expressed with at least one selenocompound-related structural gene/sulfate transporter or phosphate transporter/reactive oxygen species (ROS) scavenging structural gene/isoflavone-related structural gene, respectively. Then, we identified a total of 87 expressed miRNAs by Se disposure, in which 11 miRNAs, including miR171f-3p, miR390b-3P, miR-N111b, miR-N118, miR-N30, miR-N38-3P, miR-N61a, miR-N61b, miR-N80-3p, miR-N84-3P, and miR-N90.2-3P, were significantly upregulated. We also identified a total of 1172 target genes for the 87 expressed miRNAs. Gene Ontology enrichment analysis of these target genes showed that regulation of transcription, DNA-templated, integral component of membrane, nucleus, ATP binding, and plasma membrane are the top five subclassifications. Finally, we revealed that 5 miRNAs targeted 10 regulatory protein genes, which are highly correlated with at least one selenocompound-related structural gene or transporter gene; 5 miRNAs targeted 10 regulatory protein genes, which are highly correlated with at least one ROS scavenging structural gene; and 5 miRNAs targeted 9 regulatory protein genes, which are potentially involved in the isoflavone biosynthesis. Overall, the study provides us the comprehensive insight into the roles of regulatory proteins and miRNAs in response to Se stimuli in P. lobata.
Single-molecule visualization of human RECQ5 interactions with single-stranded DNA recombination intermediates
Authors: Xue Chaoyou , Molnarova Lucia , Steinfeld Justin B , Zhao Weixing , Ma Chujian , Spirek Mario , Kaniecki Kyle , Kwon Youngho , Beláň Ondrej , Krejci Katerina , Boulton Simon J , Sung Patrick , Greene Eric C , Krejci Lumir
Published: December 2020

RECQ5 is one of five RecQ helicases found in humans and is thought to participate in homologous DNA recombination by acting as a negative regulator of the recombinase protein RAD51. Here, we use kinetic and single molecule imaging methods to monitor RECQ5 behavior on various nucleoprotein complexes. Our data demonstrate that RECQ5 can act as an ATP-dependent single-stranded DNA (ssDNA) motor protein and can translocate on ssDNA that is bound by replication protein A (RPA). RECQ5 can also translocate on RAD51-coated ssDNA and readily dismantles RAD51–ssDNA filaments. RECQ5 interacts with RAD51 through protein–protein contacts, and disruption of this interface through a RECQ5–F666A mutation reduces translocation velocity by ∼50%. However, RECQ5 readily removes the ATP hydrolysis-deficient mutant RAD51–K133R from ssDNA, suggesting that filament disruption is not coupled to the RAD51 ATP hydrolysis cycle. RECQ5 also readily removes RAD51–I287T, a RAD51 mutant with enhanced ssDNA-binding activity, from ssDNA. Surprisingly, RECQ5 can bind to double-stranded DNA (dsDNA), but it is unable to translocate. Similarly, RECQ5 cannot dismantle RAD51-bound heteroduplex joint molecules. Our results suggest that the roles of RECQ5 in genome maintenance may be regulated in part at the level of substrate specificity.
The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction
Authors: Smith Ewan M , Benbahouche Nour El Houda , Morris Katherine , Wilczynska Ania , Gillen Sarah , Schmidt Tobias , Meijer Hedda A , Jukes-Jones Rebekah , Cain Kelvin , Jones Carolyn , Stoneley Mark , Waldron Joseph A , Bell Cameron , Fonseca Bruno D , Blagden Sarah , Willis Anne E , Bushell Martin
Published: December 2020

The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. This is achieved, in part, via the co-ordinated regulation of mRNAs that contain a terminal oligopyrimidine tract (TOP) at their 5′ends, although the mechanisms by which this occurs downstream of mTOR signalling are still unclear. We used RNA-binding protein (RBP) capture to identify changes in the protein-RNA interaction landscape following mTOR inhibition. Upon mTOR inhibition, the binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. Importantly, non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state, even under control conditions. The mRNA interactome of the LARP1-associated protein PABPC1 was found to have a high degree of overlap with that of LARP1 and our data show that PABPC1 is required for the association of LARP1 with its specific mRNA targets. Finally, we demonstrate that mRNAs, including those encoding proteins critical for cell growth and survival, are translationally repressed when bound by both LARP1 and PABPC1.
The fission yeast Pin1 peptidyl-prolyl isomerase promotes dissociation of Sty1 MAPK from RNA polymerase II and recruits Ssu72 phosphatase to facilitate oxidative stress induced transcription
Authors: Wang Yi-Ting , Hsiao Wan-Yi , Wang Shao-Win
Published: December 2020

Pin1 is a peptidyl-prolyl isomerase that regulates the structure and function of eukaryotic RNA polymerase II (Pol II) through interaction with the C-terminal domain (CTD) of Rpb1, the largest subunit of Pol II. We demonstrated that this function is important for cellular response to oxidative stress in the fission yeast Schizosaccharomyces pombe. In response to oxidative stress, the Atf1 transcription factor targets Sty1, the mitogen-activated protein kinase (MAPK), to specific stress-responsive promoters. Anchored Sty1 recruits Pol II through direct association with Rpb1-CTD and phosphorylates the reiterated heptad sequence at Serine 5. Pin1 binds phosphorylated CTD to promote dissociation of Sty1 from it, and directly recruits Ssu72 phosphatase to facilitate dephosphorylation of CTD for transcription elongation. In the absence of Pin1, the association of Sty1-Atf1 with Rpb1 persists on stress-responsive promoters failed to generate transcripts of the corresponding genes effectively. The identified characteristic features of the fission yeast Pin1 are conserved in humans. We demonstrated that elevated Pin1 level in cancer cells might help to sustain survival under oxidative stress generated from their altered metabolic pathways. Together, these results suggest a conserved function of Pin1 in cellular response to oxidative stress among eukaryotic cells that might have clinical implication.
Tumor cell network integration in glioma represents a stemness feature
Authors: Xie Ruifan , Kessler Tobias , Grosch Julia , Hai Ling , Venkataramani Varun , Huang Lulu , Hoffmann Dirk C , Solecki Gergely , Ratliff Miriam , Schlesner Matthias , Wick Wolfgang , Winkler Frank
Published: December 2020

Background

Malignant gliomas including glioblastomas are characterized by a striking cellular heterogeneity, which includes a subpopulation of glioma cells that becomes highly resistant by integration into tumor microtube (TM)-connected multicellular networks.

Methods

A novel functional approach to detect, isolate, and characterize glioma cell subpopulations with respect to in vivo network integration is established, combining a dye staining method with intravital two-photon microscopy, Fluorescence-Activated Cell Sorting (FACS), molecular profiling, and gene reporter studies.

Results

Glioblastoma cells that are part of the TM-connected tumor network show activated neurodevelopmental and glioma progression gene expression pathways. Importantly, many of them revealed profiles indicative of increased cellular stemness, including high expression of nestin. TM-connected glioblastoma cells also had a higher potential for reinitiation of brain tumor growth. Long-term tracking of tumor cell nestin expression in vivo revealed a stronger TM network integration and higher radioresistance of the nestin-high subpopulation. Glioblastoma cells that were both nestin-high and network-integrated were particularly able to adapt to radiotherapy with increased TM formation.

Conclusion

Multiple stem-like features are strongly enriched in a fraction of network-integrated glioma cells, explaining their particular resilience.
Global blue carbon accumulation in tidal wetlands increases with climate change
Authors: Wang Faming , Sanders Christian J , Santos Isaac R , Tang Jianwu , Schuerch Mark , Kirwan Matthew L , Kopp Robert E , Zhu Kai , Li Xiuzhen , Yuan Jiacan , Liu Wenzhi , Li Zhi'an
Published: December 2020

Coastal tidal wetlands produce and accumulate significant amounts of organic carbon (C) that help to mitigate climate change. However, previous data limitations have prevented a robust evaluation of the global rates and mechanisms driving C accumulation. Here, we go beyond recent soil C stock estimates to reveal global tidal wetland C accumulation and predict changes under relative sea level rise, temperature and precipitation. We use data from literature study sites and our new observations spanning wide latitudinal gradients and 20 countries. Globally, tidal wetlands accumulate 53.65 (95%CI: 48.52–59.01) Tg C yr−1, which is ∼30% of the organic C buried on the ocean floor. Modeling based on current climatic drivers and under projected emissions scenarios revealed a net increase in the global C accumulation by 2100. This rapid increase is driven by sea level rise in tidal marshes, and higher temperature and precipitation in mangroves. Countries with large areas of coastal wetlands, like Indonesia and Mexico, are more susceptible to tidal wetland C losses under climate change, while regions such as Australia, Brazil, the USA and China will experience a significant C accumulation increase under all projected scenarios.
High-velocity impact of a hybrid CBN nanotubes
Authors: Armani Enzo , Autreto Pedro A S
Published: December 2020

Nanomaterials under extreme conditions can behave in a completely different manner. High-velocity impact, for example, can produce nanoribbons without any chemical approach via carbon or boron nitride nanotubes unzipping. Although hybrid nanostructures have been used to create stronger structures, few studies on these materials under extreme conditions have been employed. In this work, we studied, using fully atomistic reactive molecular dynamics simulations an experimentally synthesized hybrid nanotube (boron nitride and carbon nanotubes concentrically assembled) under the high-velocity impact. Our results show that the combination of elastic and brittle materials can produce different structures, such as nanoribbons and boron nitride atomic chains. These results can have a significant impact on the production of new nanostructures.
Collateral Runs
Authors: Infante Sebastian , Vardoulakis Alexandros P
Published: December 2020

This paper models an unexplored source of liquidity risk large broker-dealers face: a withdrawal of collateral providers. By setting different contracting terms on repurchase agreements with cash borrowers and lenders, dealers can source funds for their own activities. Cash borrowers internalize the risk of losing their collateral in case their dealer defaults, prompting them to withdraw it. This incentive creates strategic complementarities among collateral providers, reducing a dealer’s liquidity position and compromising their solvency. Collateral runs are triggered by a contraction in dealers’ assets making them markedly different than traditional wholesale funding runs. Mitigating these risks involves different policy recommendations.
Incidence and severeness of COVID-19 hospitalization in patients with inflammatory rheumatic disease: a nationwide cohort study from Denmark
Authors: Cordtz René , Lindhardsen Jesper , Soussi Bolette G , Vela Jonathan , Uhrenholt Line , Westermann Rasmus , Kristensen Salome , Nielsen Henrik , Torp-Pedersen Christian , Dreyer Lene
Published: December 2020

Objectives

To estimate the incidence of COVID-19 hospitalization in patients with inflammatory rheumatic disease (IRD); in patients with RA treated with specific DMARDs; and the incidence of severe COVID-19 infection among hospitalized patients with RA.

Methods

A nationwide cohort study from Denmark between 1 March and 12 August 2020. The adjusted incidence of COVID-19 hospitalization was estimated for patients with RA; spondyloarthritis including psoriatic arthritis; connective tissue disease; vasculitides; and non-IRD individuals. Further, the incidence of COVID-19 hospitalization was estimated for patients with RA treated and non-treated with TNF-inhibitors, HCQ or glucocorticoids, respectively. Lastly, the incidence of severe COVID-19 infection (intensive care, acute respiratory distress syndrome or death) among hospital-admitted patients was estimated for RA and non-IRD sp - individudals.

Results

Patients with IRD (n = 58 052) had an increased partially adjusted incidence of hospitalization with COVID-19 compared with the 4.5 million people in the general population [hazard ratio (HR) 1.46, 95% CI: 1.15, 1.86] with strongest associations for patients with RA (n = 29 440, HR 1.72, 95% CI: 1.29, 2.30) and vasculitides (n = 4072, HR 1.82, 95% CI: 0.91, 3.64). There was no increased incidence of COVID-19 hospitalization associated with TNF-inhibitor, HCQ nor glucocorticoid use. COVID-19 admitted patients with RA had a HR of 1.43 (95% CI: 0.80, 2.53) for a severe outcome.

Conclusion

Patients with IRD were more likely to be admitted with COVID-19 than the general population, and COVID-19 admitted patients with RA could be at higher risk of a severe outcome. Treatment with specific DMARDs did not affect the risk of hospitalization.
Adult-onset Still’s disease with neurological involvement: a single-centre report
Authors: Zhao Mengzhu , Wu Di , Shen Min
Published: December 2020

Objectives

Adult-onset Still’s disease (AOSD) is a multifactorial systemic autoinflammatory disease. Neurological damage has been rarely reported in AOSD. We aimed to characterize the clinical features of AOSD patients with neurological involvement.

Methods

A total of 187 AOSD patients were admitted to Peking Union Medical College Hospital from January 2015 to August 2019. The complete medical records were reviewed in this retrospective study. Clinical features of 14 AOSD patients with neurological involvement were collected and compared with those without.

Results

The prevalence of neurological involvement in AOSD inpatients was 7.5%. The median disease duration was 4.5 months, with a range of 1–15 months. The frequent symptoms were fever [14 (100%)], rash [13 (92.9%)], liver dysfunction [11 (78.6%)], arthralgia/arthritis [10 (71.4%)] and lymphadenopathy [10 (71.4%)]. Four (28.6%) patients had macrophage activation syndrome (MAS). Aseptic meningitis was the most common presentation (64.3%) when the nervous system was involved. Other rare manifestations included cranial nerve palsy, encephalitis and cerebral infarction. The rate of MAS, serum levels of lactate dehydrogenase and ferritin were significantly higher in AOSD patients with neurological involvement than in those without. All patients received high-dose corticosteroid therapy and immunosuppressive agents and two were given tocilizumab. Clinical remission was achieved in all 14 AOSD patients with neurological involvement.

Conclusion

Neurological involvement, particularly aseptic meningitis, is not a rare complication of AOSD. It is frequently complicated by MAS. There may be a potential relationship between the neurological damage of AOSD and MAS.
Barriers and facilitators to the implementation of a novel web-based sleep apnea management platform
Authors: Chang Yoon Hee A , Folmer Robert L , Shasha Becky , Shea Judy A , Sarmiento Kathleen , Stepnowsky Carl J , Lim Diane , Pack Allan , Kuna Samuel T
Published: December 2020

Study Objective

Obstructive sleep apnea (OSA) is a highly prevalent yet underdiagnosed disorder affecting US military Veterans. The Remote Veterans Apnea Management Platform (REVAMP) is a web-based OSA management program created to improve access to care. REVAMP was launched within the Veterans Health Administration (VHA) in July 2017, with variable patient recruitment rates (from 0 to 573 patients per site) at the first 10 Veterans Affairs (VA) medical centers (Wave-1 sites). This study aimed to examine the contextual circumstances surrounding the implementation of REVAMP from the provider perspective to inform strategies to increase its uptake at future rollout sites.

Methods

A purposive sample of REVAMP site leaders from the Wave-1 sites was recruited with additional staff members being solicited as well. Semi-structured interviews were conducted. Two independent coders reviewed individual transcripts using content analysis to identify emerging themes.

Results

Fifteen individuals from Wave-1 sites were interviewed. Implementation of REVAMP was facilitated by the presence of leadership support, staff, and time dedicated to REVAMP, and perceived usefulness of REVAMP by staff as well as positive feedback from the Veterans using REVAMP. The difficulty of supporting Veteran creation of login credentials to the program and integrating REVAMP into the existing workflow were major barriers to its implementation.

Conclusion

Improving leadership engagement, simplifying the enrollment process, and enhancing the medical staff experience through shared best practice alerts were identified as actions needed to improve the penetration of REVAMP at future rollout sites.
Circadian regulation of breath alcohol concentration
Authors: Rukmini A V , Jos Anna Mini , Yeo Sing-Chen , Lee Noel , Mo Di , Mohapatra Litali , Karamchedu Swathy , Gooley Joshua J
Published: December 2020

Study Objectives

The role of the circadian clock in regulating blood/breath alcohol levels after consuming alcohol is uncertain. Our goal was to evaluate the degree to which the circadian system regulates breath alcohol concentration (BrAC) pharmacokinetic parameters.

Methods

Twenty healthy adults aged 21–30 years took part in a 4-day laboratory study. A 40-h constant routine procedure was used to assess circadian rhythms. Every 4 h, participants were given a fixed oral dose of alcohol with breathalyzer measurements taken every 5 min to construct BrAC curves. Sinusoidal models were used to test for circadian variation of the peak BrAC, the time to reach peak BrAC, the absorption rate, the elimination rate, and the time for BrAC to return to zero after alcohol was ingested.

Results

A significant circadian rhythm was detected for group-averaged peak BrAC values and the time for BrAC to return to zero, but not other BrAC variables. Peak BrAC values were lowest in the evening near the peak of the core body temperature rhythm and nadir of the salivary cortisol rhythm. Peak BrAC values increased during the night and reached their highest levels in the morning and afternoon. The time needed for BrAC to return to zero was also longest in the late morning and afternoon.

Conclusion

The circadian system modulates some BrAC pharmacokinetic parameters. In normally entrained individuals, taking the same oral dose of alcohol at different times of day can result in different BrAC responses. These findings have potential implications for alcohol-related accidents and alcohol toxicity.
Carbon Dioxide Expiration and Performance Fatigability Following Aerobic Exercise Training
Authors: Wooten Liana C. , Neville Brian T. , Guccione Andrew A. , Chin Lisa M.K. , Keyser Randall E.
Published: December 2020

Purpose:

This study examined the influence of aerobic exercise training (AET) on components of carbon dioxide expiration (VCO2), cardiorespiratory function, and fatigability.

Methods:

Twenty healthy adults completed peak cardiopulmonary exercise (CPX) and submaximal tests before and after a vigorous, 4-week AET regimen. Each test was followed by a 10-minute recovery and endurance test at 70% of peak wattage attained during CPX. Fatigability was assessed using testing durations and power output. Respiratory buffering (excess VCO2) and nonbuffering (metabolic VCO2) were calculated. Data were analyzed for significance (P < .05) using regressions and paired t-tests.

Results:

Significant improvements in all measures of fatigability were observed after AET. A significant increase in excess VCO2 was observed, although not in metabolic VCO2. Excess VCO2 was strongly predictive of fatigability measures.

Conclusion:

Significant decreases in fatigability are often observed in clinical populations such as obstructive or restrictive lung disease or pulmonary hypertension following AET, even when peak cardiorespiratory function does not appear to adapt. Decreases in fatigability seem to predict longevity with no yet identified mechanism. These results suggest that respiratory buffering and metabolic components of VCO2 may adapt independently to AET, introducing foundational plausibility for an influence of respiratory buffering adaptation to AET on fatigability status.
Precision Medicine in Ossiculoplasty
Authors: Mukherjee Payal , Cheng Kai , Chung Johnson , Grieve Stuart M. , Solomon Michael , Wallace Gordon
Published: December 2020

Introduction:

Long term results of ossiculoplasty surgery are considered poor with displacement and extrusion amongst the common reasons for failure. Application of 3Dimensional (3D) printing may help overcome some of these barriers, however digital methods to attain accurate 3D morphological studies of ossicular anatomy are lacking, exacerbated by the limitation of resolution of clinical imaging.

Methods:

20 human cadaveric temporal bones were assessed using micro computed tomography (CT) imaging to demonstrate the lowest resolution required for accurate 3D reconstruction. The bones were then scanned using conebeam CT (125 μm) and helical CT (0.6 mm). 3D reconstruction using clinical imaging techniques with microCT imaging (40 μm resolution) as a reference was assessed. The incus was chosen as the focus of study. Two different methods of 3D printing techniques were assessed.

Results:

A minimum resolution of 100 μm was needed for adequate 3D reconstruction of the ossicular chain. Conebeam CT gave the most accurate data on 3D analysis, producing the smallest mean variation in surface topography data relative to microCT (mean difference 0.037 mm, p < 0.001). Though the incus varied in shape in between people, paired matches were identical. Thus, the contralateral side can be used for 3D printing source data if the ipsilateral incus is missing. Laser based 3D printing was superior to extrusion based printing to achieve the resolution demands for 3D printed ossicles.

Conclusion:

Resolution of modern imaging allows 3D reconstructions and 3D printing of human ossicles with good accuracy, though it is important to pay attention to thresholding during this process.
Management of Intractable Petrous Bone Cholesteatoma With a Combined Translabyrinthine–Transsphenoidal Approach
Authors: Morino Tsunetaro , Yamamoto Yutaka , Yamamoto Kazuhisa , Komori Manabu , Asaka Daiya , Kojima Hiromi
Published: December 2020

Objective:

To evaluate whether a combined translabyrinthine–transsphenoidal approach can be used to achieve adequate surgical resection of an extensive petrous bone cholesteatoma and create a debris drainage route for the residual cholesteatoma that is maintained long-term.

Patient:

A 71-year-old man with residual petrous temporal bone cholesteatoma that had spread extensively to the internal carotid artery and posterior cranial fossa.

Intervention:

Surgical resection of the cholesteatoma via a translabyrinthine approach and creation of a debris drainage route into the nasopharynx via a transsphenoidal approach.

Main Outcome Measures:

Control of unresectable petrous temporal bone cholesteatoma and occurrence of cholesteatoma- or surgery-related complications.

Results:

Although complete removal of the cholesteatoma was attempted via a translabyrinthine approach, this was not possible because the epithelium of the cholesteatoma was strongly attached to the internal carotid artery and posterior cranial fossa. A debris drainage route leading to the nasopharynx was created by drilling the clivus on the side of the lesion via a transsphenoidal approach. The patient has had no complications since surgery. The drainage route remains open, and the cholesteatoma has been controlled for 57 months.

Conclusions:

A markedly advanced petrous temporal bone cholesteatoma can be managed safety and reliably by combining a translabyrinthine approach with a transsphenoidal approach. Creation of a debris drainage route into the nasopharynx can prevent isolation of the cholesteatoma and mastoid cavity problems after surgery. This one-stage surgery may be a suitable method for keeping cholesteatoma under control in patients with unresectable petrous bone cholesteatoma.
Posttraumatic Dizziness: Navigating the Maze Towards Accurate Vestibular Diagnosis and Treatment
Authors: Grzesiak Melissa , Carender Wendy , Basura Gregory J.
Published: December 2020

Objective:

Highlight the importance of establishing a differential diagnosis to identify and treat multiple origins of dizziness in a patient following traumatic brain injury (TBI).

Patient:

73-year-old man with TBI and temporal bone fracture developed posttraumatic bilateral multiple canal benign paroxysmal positional vertigo (BPPV).

Intervention:

Multi-disciplinary diagnostic evaluation and vestibular rehabilitation (VR) treatment focused on canalith repositioning maneuvers (CRMs) and central adaptation.

Main Outcome Measures:

Diagnostic imaging, audiometric testing, clinical evaluation including video recordings of patterns of nystagmus, Dizziness Handicap Inventory (DHI).

Results:

Systematic clinical examination identified multiple semicircular canal BPPV in addition to a suspected underlying unilateral hypofunction. Treatment focused on the appropriate CRMs and adaptation exercises. DHI scores improved significantly and patient returned to work and recreational activities.

Conclusion:

This Clinical Capsule Report highlights the importance of a comprehensive clinical evaluation of the TBI patient with dizziness when making an accurate diagnosis and treatment plan. Due to the complexity of differentiating between multiple canal BPPV in addition to other central and vestibular disorders, it is imperative for the clinician to have a clear understanding of nystagmus patterns for multicanal BPPV as well as other vestibular pathology.
Social and racial inequalities in COVID-19 risk of hospitalisation and death across São Paulo state, Brazil
Authors: Li Sabrina L , Pereira Rafael H M , Prete Carlos A , Zarebski Alexander E , Emanuel Lucas , Alves Pedro JH , Peixoto Pedro S , Braga Carlos KV , de Souza Santos Andreza A , de Souza William M , Barbosa Rogerio J , Buss Lewis F , Mendrone Alfredo , de Almeida-Neto Cesar , Ferreira Suzete C , Salles Nanci A , Marcilio Izabel , Wu Chieh-Hsi , Gouveia Nelson , Nascimento Vitor H , Sabino Ester C , Faria Nuno R , Messina Jane P
Published: December 2020

Background

Little evidence exists on the differential health effects of COVID-19 on disadvantaged population groups. Here we characterise the differential risk of hospitalisation and death in São Paulo state, Brazil and show how vulnerability to COVID-19 is shaped by socioeconomic inequalities.

Methods

We conducted a cross-sectional study using hospitalised severe acute respiratory infections (SARI) notified from March to August 2020, in theSistema de Monitoramento Inteligente de São Paulo(SIMI-SP) database. We examined the risk of hospitalisation and death by race and socioeconomic status using multiple datasets for individual-level and spatio-temporal analyses. We explained these inequalities according to differences in daily mobility from mobile phone data, teleworking behaviour, and comorbidities.

Findings

Throughout the study period, patients living in the 40% poorest areas were more likely to die when compared to patients living in the 5% wealthiest areas (OR: 1·60, 95% CI: 1·48 – 1·74) and were more likely to be hospitalised between April and July, 2020 (OR: 1·08, 95% CI: 1·04 – 1·12). Black andPardoindividuals were more likely to be hospitalised when compared to White individuals (OR: 1·37, 95% CI: 1·32 – 1·41; OR: 1·23, 95% CI: 1·21 – 1·25, respectively), and were more likely to die (OR: 1·14, 95% CI: 1·07 – 1·21; 1·09, 95% CI: 1·05 – 1·13, respectively).

Interpretation

Low-income and Black andPardocommunities are more likely to die with COVID-19. This is associated with differential access to healthcare, adherence to social distancing, and the higher prevalence of comorbidities.

Funding

This project was supported by a Medical Research Council-São Paulo Research Foundation (FAPESP) CADDE partnership award (MR/S0195/1 and FAPESP 18/14389-0) (http://caddecentre.org/). This work received funding from the U.K. Medical Research Council under a concordat with the U.K. Department for International Development.
Increased prefrontal top-down control in older adults predicts motor performance and age-group association
Authors: Loehrer Philipp Alexander , Nettersheim Felix Sebastian , Oehrn Carina , Homberg Fabienne , Tittgemeyer Marc , Timmermann Lars , Weber Immo
Published: December 2020

Bimanual motor control declines during ageing, affecting the ability of older adults to maintain independence. An important underlying factor is cortical atrophy, particularly affecting frontal and parietal areas in older adults. As these regions and their interplay are highly involved in bimanual motor preparation, we investigated age-related connectivity changes between prefrontal and premotor areas of young and older adults during the preparatory phase of complex bimanual movements using high-density electroencephalography. Generative modelling showed that excitatory interhemispheric prefrontal to premotor coupling in older adults predicted age-group affiliation and was associated with poor motor-performance. In contrast, excitatory intrahemispheric prefrontal to premotor coupling enabled older adults to maintain motor-performance at the cost of lower movement speed. Our results disentangle the complex interplay in the prefrontal-premotor network during movement preparation underlying reduced bimanual control and the well-known speed-accuracy trade-off seen in older adults.
A comparative study of deconvolution methods for RNA-seq data under a dynamic testing landscape
Authors: Jin Haijing , Liu Zhandong
Published: December 2020

Deconvolution analyses have been widely used to track compositional alternations of cell-types in gene expression data. Even though numerous novel methods have been developed in recent years, researchers are still having difficulty selecting optimal deconvolution methods due to the lack of comprehensive benchmarks relative to the newly developed methods. To systematically reveal the pitfalls and challenges of deconvolution analyses, we studied the impact of several technical and biological factors such as simulation model, quantification unit, component number, weight matrix, and unknown content by constructing three benchmarking frameworks that cover comparative analysis of 11 popular deconvolution methods under 1,766 conditions. We hope this study can provide new insights to researchers for future application, standardization, and development of deconvolution tools on RNA-seq data.
IGI-LuNER: single-well multiplexed RT-qPCR test for SARS-CoV-2
Authors: Stahl Elizabeth C. , Tsuchida Connor A. , Hamilton Jennifer R. , Lin-Shiao Enrique , McDevitt Shana L. , Moehle Erica A. , Witkowsky Lea B. , Tsui C. Kimberly , Pestal Kathleen , Gildea Holly K. , McElroy Matthew , Keller Amanda , Sylvain Iman , Williams Clara , Hirsh Ariana , Ciling Alison , Ehrenberg Alexander J. ,   IGI SARS-CoV-2 consortium, Urnov Fyodor D. , Ringeisen Bradley R. , Giannikopoulos Petros , Doudna Jennifer A.
Published: December 2020

Commonly used RT-qPCR-based SARS-CoV-2 diagnostics require 2-3 separate reactions or rely on detection of a single viral target, adding time and cost or risk of false-negative results. Currently, no test combines detection of widely used SARS-CoV-2 E- and N-gene targets and a sample control in a single, multiplexed reaction. We developed the IGI-LuNER RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (NER). This combined, cost-effective test can be performed in 384-well plates with detection sensitivity suitable for clinical reporting, and will aid in future sample pooling efforts, thus improving throughput of SARS-CoV-2 detection.

Graphical Abstract
The first dinosaur egg remains a mystery
Authors: Legendre Lucas J. , Rubilar-Rogers David , Vargas Alexander O. , Clarke Julia A.
Published: December 2020

A recent study by Norell et al. (2020) described new egg specimens for two dinosaur species, identified as the first soft-shelled dinosaur eggs. The authors used phylogenetic comparative methods to reconstruct eggshell type in a sample of reptiles, and identified the eggs of dinosaurs and archosaurs as ancestrally soft-shelled, with three independent acquisitions of a hard eggshell among dinosaurs. This result contradicts previous hypotheses of hard-shelled eggs as ancestral to archosaurs and dinosaurs. Here we estimate the ancestral condition for dinosaur and archosaur eggs by reanalyzing the original data from Norell et al. and that from a recent study on reptile eggshells (Legendre et al., 2020) with the addition of these new dinosaur specimens. We show that the recovery of dinosaur eggs as ancestrally soft-shelled is conditioned by the discretization of a continuous character (eggshell thickness), the exclusion of turtle outgroups from the original sample, and a lack of branch length information. When using a larger sample, calibrated trees, and a definition of hard-shelled eggs referencing their unique prismatic structure, we recover dinosaur and archosaur eggs as either hard-shelled or uncertain (i.e. equal probability for hard- and soft-shelled). This remaining ambiguity is due to uncertainty in the assessment of eggshell type in two dinosaur species, i.e. ∼1% of the total sample. We conclude that more reptile egg specimens and a strict comparative framework are necessary to decipher the evolution of dinosaur eggs in a phylogenetic context.
The function of SIRT3 explored through the substrate interaction network
Authors: Nahálková Jarmila
Published: December 2020

SIRT3 is the mitochondrial protein lysine deacetylase with a prominent role in the maintenance of mitochondrial integrity vulnerable in the range of diseases. The present study examines the SIRT3 substrate interaction network for the identification of its biological functions in the cellular anti-aging mechanisms. The pathway enrichment, the protein function prediction, and the protein node prioritization analysis were performed based on 407 SIRT3 substrates, which were collected by the data mining. The substrates are interlinked by 1230 direct protein-protein interactions included in the GeneMania database. The analysis of the SIRT3 substrate interaction network highlighted Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and non-alcoholic fatty liver disease (NAFLD) as the most associated with SIRT3 lysine deacetylase activity. The most important biological functions of SIRT3 substrates are within the respiratory electron transport chain, tricarboxylic acid cycle and fatty acid, triacylglycerol, and ketone body metabolism. In brown adipose tissue, SIRT3 activity contributes to the adaptive thermogenesis by the increase of energy production of the organisms. SIRT3 exhibits several modes of neuroprotective actions in the brain and liver including prevention of the mitochondrial damages due to the respiratory electron transfer chain failure, the quenching of ROS, the inhibition of the mitochondrial membrane potential loss, and the regulation of mitophagy. Related to its role in Alzheimer’s disease, SIRT3 activation performs as a repressor of BACE1 through SIRT3-LKB1-AMPK-CREB-PGC-1α-PPARG-BACE1 (SIRT3-BACE1) pathway, which was created based on the literature mining and by employing Wikipathways application. The pathway enrichment analysis of the extended interaction network of the SIRT3-BACE1 pathway nodes displayed the functional relation to the circadian clock, which also deteriorates during the progress of AD and it is the causative of AD, PD, and HD. The use of SIRT3 activators in combination with the stimulating effect of regular exercise is further discussed as an attractive option for the improvement of cognitive decline during aging and the progressive stages of neurodegeneration.
Distinct cortical correlation structures of fractal and oscillatory neuronal activity
Authors: Chaoul Andrea Ibarra , Siegel Markus
Published: December 2020

Electrophysiological population signals contain oscillatory and fractal (1/frequency) components. So far research has largely focused on oscillatory activity and only recently interest in fractal population activity has gained momentum. Accordingly, while the cortical correlation structure of oscillatory population activity has been characterized, little is known about the correlation of fractal neuronal activity. To address this, we investigated fractal neuronal population activity in the human brain using resting-state magnetoencephalography (MEG). We combined source-analysis, signal orthogonalization and irregular-resampling auto-spectral analysis (IRASA) to systematically characterize the cortical distribution and correlation of fractal neuronal activity. We found that fractal population activity is robustly correlated across the cortex and that this correlation is spatially well structured. Furthermore, we found that the cortical correlation structure of fractal activity is similar but distinct from the correlation structure of oscillatory neuronal activity. Anterior cortical regions showed the strongest differences between oscillatory and fractal correlation patterns. Our results suggest that correlations of fractal population activity serve as robust markers of cortical network interactions. Furthermore, our results show that fractal and oscillatory signal components provide non-redundant information about large-scale neuronal correlations. This may reflect at least partly distinct neuronal mechanisms underlying and reflected by oscillatory and fractal neuronal population activity.
TrancriptomeReconstructoR: data-driven annotation of complex transcriptomes
Authors: Ivanov Maxim , Sandelin Albin , Marquardt Sebastian
Published: December 2020

Background

The quality of gene annotation determines the interpretation of results obtained in transcriptomic studies. The growing number of genome sequence information calls for experimental and computational pipelines forde novotranscriptome annotation. Ideally, gene and transcript models should be called from a limited set of key experimental data.

Results

We developed TranscriptomeReconstructoR, an R package which implements a pipeline for automated transcriptome annotation. It relies on integrating features from independent and complementary datasets: i) full-length RNA-seq for detection of splicing patterns and ii) high-throughput 5’ and 3’ tag sequencing data for accurate definition of gene borders. The pipeline can also take a nascent RNA-seq dataset to supplement the called gene model with transient transcripts.

We reconstructedde novothe transcriptional landscape of wild typeArabidopsis thalianaseedlings as a proof-of-principle. A comparison to the existing transcriptome annotations revealed that our gene model is more accurate and comprehensive than the two most commonly used community gene models, TAIR10 and Araport11. In particular, we identify thousands of transient transcripts missing from the existing annotations. Our new annotation promises to improve the quality ofA.thalianagenome research.

Conclusions

Our proof-of-concept data suggest a cost-efficient strategy for rapid and accurate annotation of complex eukaryotic transcriptomes. We combine the choice of library preparation methods and sequencing platforms with the dedicated computational pipeline implemented in the TranscriptomeReconstructoR package. The pipeline only requires prior knowledge on the reference genomic DNA sequence, but not the transcriptome. The package seamlessly integrates with Bioconductor packages for downstream analysis.
Linear summation of metabotropic postsynaptic potentials follows coactivation of neurogliaform interneurons
Authors: Ozsvár Attila , Komlósi Gergely , Oláh Gáspár , Baka Judith , Molnár Gábor , Tamás Gábor
Published: December 2020

Summation of ionotropic receptor-mediated responses is critical in neuronal computation by shaping input-output characteristics of neurons. However, arithmetics of summation for metabotropic signals are not known. We characterized the combined ionotropic and metabotropic output of neocortical neurogliaform cells (NGFCs) using electrophysiological and anatomical methods. These experiments revealed that GABA receptors are activated up to 1.8 microns from release sites and confirmed coactivation of putative NGFCs in superficial cortical layers in vivo. Triple recordings from presynaptic NGFCs converging to a postsynaptic neuron revealed sublinear summation of ionotropic GABAAresponses and linear summation of metabotropic GABABresponses. Based on a model combining distances of volume transmission from release sites and distributions of all NGFC axon terminals, we postulate that 2 to 3 NGFCs provide input to a point in the neuropil. We suggest that interactions of metabotropic GABAergic responses remain linear even if most superficial layer interneurons specialized to recruit GABABreceptors are simultaneously active.
High-throughput, low-cost and rapid DNA sequencing using surface-coating techniques
Authors: Qin Yanzhe , Koehler Stephan , Zhao Shengming , Mai Ruibin , Liu Zhuo , Lu Hao , Xing Chengmei
Published: December 2020

The speed1–3, expense1–4and throughput2of genomic sequencing impose limitations on its use for time-sensitive acute cases, such as rare4,5or antibiotic resistant infections6, and large-scale testing that is necessary for containing COVID-19 outbreaks using source-tracing7–9. The major bottleneck for increasing the bandwidth and decreasing operating costs of next-generation sequencers (NGS) is the flow cell that supplies reagents for the biochemical processes; this subsystem has not significantly improved since 200510–12. Here we report a new method for sourcing reagents based on surface coating technology (SCT): the DNA adhered onto the biochip is directly contacted by a reagent-coated polymeric strip. Compared with flow cells the reagent layers are an order of magnitude thinner while both the reagent exchange rate and biochip area are orders of magnitude greater. These improvements drop the turn-around time from days to twelve hours and the cost for whole genome sequencing (WGS) from about $1000 to $15, as well as increase data production by several orders of magnitude. This makes NGS more affordable than many blood tests while rapidly providing detailed genomic information about microbial and viral pathogens6,13, cancers14and genetic disorders for targeted treatments6and personalized medicine6,15. This data can be pooled in population-wide databases for accelerated research and development as well providing detailed real-time data for tracking and containing outbreaks, such as the current COVID-19 pandemic.
Synchrony of Non-isochronous Signals in an Acoustically Communicating Katydid
Authors: Nityananda Vivek , Balakrishnan Rohini
Published: December 2020

The ability to entrain to auditory stimuli has been a powerful method to investigate the comparative rhythm abilities of different animals. While synchrony to regular (isochronous) rhythms is well documented, synchrony to non-isochronous stimuli, with multiple components at unequal time intervals, is rarer. Several katydid species with isochronous calls have been shown to achieve synchrony as part of their natural calling interactions in multi-individual choruses. Yet no study so far has demonstrated synchrony in any insect with a non-isochronous call. Using natural calling behaviour and playback experiments, we investigated acoustic synchrony and the mechanisms underlying it in the katydid speciesMecopoda‘Two Part Caller’. This species has a complex non-isochronous call consisting of a long trill followed by two or more chirps. We found that individual males synchronized trills and, to a lesser extent, chirps. Further investigation of trill synchrony showed that timing of trills is modified by external trills but not chirps. Chirp synchrony is modified by external chirps but also by trills. We suggest a two-oscillator model underlying synchrony in this species and discuss the implications for the evolution of acoustic synchrony.
Quantifying the influence of space on social group structure
Authors: Evans Julian , Liechti Jonas I. , Silk Matthew J. , Bonhoeffer Sebastian , König Barbara
Published: December 2020

When studying social behaviour, it can be important to determine whether the behaviour being recorded is actually driven by the social preferences of individuals. Many studies of animal social networks therefore attempt to disentangle social preferences from spatial preferences or restrictions. As such, there are a large number of techniques with which to test whether results from network analysis can be explained by random interactions, or interactions driven by similarities in space use. Selecting which of these methods to use will require determining to what extent space might influence social structure. Here we present a simple method (Social Spatial Community Assignment Test) to quantify the similarity between social and spatial group structure. We then apply this method to both simulated and empirical data of social interactions to demonstrate that it can successfully tease apart social and spatial explanations for groups. We first show that it can resolve the relative importance of space and social preferences in three simulated datasets in which interaction patterns are driven purely by space use, purely by social preferences or a mixture of the two. We then apply it to empirical data from a long-term study of free-ranging house mice. We find that while social structure is similar to spatial structure, there is still evidence for individuals possessing social preferences, with the importance of these preferences fluctuating between seasons. Our method provides a robust way of assessing the overlap between spatial and social structure, which will be invaluable to researchers when investigating the underlying drivers of social structure in wild populations.