bluuebunny/crossref_metadata_2025 huggingface dataset:
The Interaction Between The Noradrenergic Neurons In The Locus Coeruleus And Beta-1 Adrenergic Receptor (β1-AR) In The Cardiomyocytes Was Implicated In Modulating SUDEP
Authors: Lian XiTing , Yu Qian , Ma HaiXiang , Gu LeYuan , Xu Qing , Wang YuLing , Shen Yue , Zhang HongHai
Published: January 2022

Sudden unexpected death of epilepsy (SUDEP) is the leading cause of of death in patients with epilepsy. Due to the complicated pathogenesis of SUDEP, however, the exact mechanism of SUDEP remains elusive. Currently, although it is recognized that the seizure-induced respiratory arrest (S-IRA) may be a main cause for SUDEP, other factors resulting in SUDEP can not be excluded e.g arrhythmias. Our previous findings indicated that the incidence of S-IRA and SUDEP evoked by acoustic stimulation or pentetrazol (PTZ) injection was significantly reduced by atomoxetine, a norepinephrine reuptake inhibitor (NRI), suggesting that noradrenergic neurotransmission modulates S-IRA and SUDEP. Given that norepinephrine acts on the target to modulate respiratory and circulation function by targeting adrenergic receptor α and beta (a-AR and β-AR) and the arrhythmias can be contributed to SUDEP. Meanwhile, to further test whether cardiac factors are implicated in S-IRA and SUDEP, we choose esmolol hydrochloride, a selective antagonist of β1-AR to test it in our models. Our findings demonstrated that the lower incidence of S-IRA and SUDEP evoked by acoustic stimulation or PTZ injection in DBA/1 mice by administration with atomoxetine was significantly reversed by intraperitoneal (IP) of esmolol hydrochloride. Importantly, the data of electrocardiogram (ECG) showed that the cardiac arrhythmia including the ventricular tachycardia, ventricular premature beat and atrioventricular block can be evoked by acoustic stimulation or PTZ injection in our model. Administration of atomoxetine significantly reduced these arrhythmias and the incidence of S-IRA and SUDEP in our models. However, administration of esmolol hydrochloride with the dose without affecting ECG and mortality changing of DBA/1 significantly blocking the protective effects of atomoxetine on S-IRA and SUDEP in our models. Thus, the dysfunction of respiratory and circulation may be implicated in the pathogenesis of S-IRA and SUDEP. Enhancing the central norepinephrinergic neurotransmission in the brain contributes to inhibition of seizure-induced respiratory arrest by targeting β1-AR locating in the cardiomyocytes. Furthermore, the suppression effects of S-IRA by atomoxetine was significantly reversed by the norepinephrine neuronal degradation in the LC in our models. Furthermore, PTZ-induced Tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of norepinephrine, activity but not TH content from the serum of left ventricle and the whole heart tissue was reduced following the S-IRA. Our findings will show a new light on decoding the pathogenesis of SUDEP concerning the pathway between the LC and heart.
A theory of cortical map formation in the visual brain
Authors: Najafian Sohrab , Koch Erin , Teh Kai Lun , Jin Jianzhong , Rahimi-Nasrabadi Hamed , Zaidi Qasim , Kremkow Jens , Alonso Jose-Manuel
Published: January 2022

The cerebral cortex receives multiple afferents from the thalamus that segregate by stimulus modality forming cortical maps for each sense. In vision, the primary visual cortex maps the multiple dimensions of the visual stimulus in patterns that vary across species for reasons unknown. Here we introduce a general theory of cortical map formation, which proposes that map diversity emerges from species variations in the thalamic afferent density sampling sensory space. In the theory, increasing afferent sampling density enlarges the cortical domains representing the same visual point, allowing the segregation of afferents and cortical targets by multiple stimulus dimensions. We illustrate the theory with an afferent-density model that accurately replicates the maps of different species through afferent segregation followed by thalamocortical convergence pruned by visual experience. Because thalamocortical pathways use similar mechanisms for axon segregation and pruning, the theory may extend to other sensory areas of the mammalian brain.
Control of Leaf Width by the APC/CTAD1-WL1-NAL1 Pathway in Rice
Authors: You Jing , Xiao Wenwen , Zhou Yue , Ye Li , Yu Peng , Yu Guoling , Zhang Xinfang , He Zhifeng , Xiang Yan , Sang Xianchun , Li Yunfeng , Zhao Fangming , Ling Yinghua , He Guanghua , Zhang Ting
Published: January 2022

Leaf morphology is one of the most important features of the ideal plant architecture. However, the genetic and molecular mechanisms controlling leaf morphology in crops remain largely unknown, despite their central importance. Here we demonstrate that the APC/CTAD1-WL1-NAL1 pathway regulates leaf width in rice, and mutation of WL1 leads to width leaf variation. WL1 interacts with TAD1 and is degraded by APC/CTAD1, with the loss of TAD1 function resulting in narrow leaves. The WL1 protein directly binds to the regulatory region of NAL1 and recruits the corepressor TOPLESS-RELATED PROTEIN to inhibit NAL1 expression by down-regulating the level of histone acetylation of chromatin. Furthermore, biochemical and genetic analyses revealed that TAD1, WL1, and NAL1 function in a common pathway to control leaf width. Our study establishes an important framework for the APC/CTAD1-WL1-NAL1 pathway-mediated control of leaf width in rice and introduces novel perspectives for using this regulatory pathway for improving crop plant architecture.
Innovative multidimensional models in a high-throughput-format for different cell types of endocrine origin
Authors: Bornstein Stefan , Shapiro Igor , Malyukov Maria , Züllig Richard , Luca Edlira , Gelfgat Evgeny , Beuschlein Felix , Nölting Svenja , Berruti Alfredo , Sigala Sandra , Peitzsch Mirko , Steenblock Charlotte , Ludwig Barbara , Kugelmeier Patrick , Hantel Constanze
Published: January 2022

The adrenal gland provides an important function by integrating neuronal, immune, vascular, metabolic and endocrine signals under a common organ capsule. It is the central organ of the stress response system and has been implicated in numerous stress-related disorders. While for other diseases, regeneration of healthy organ tissue has been aimed at such approaches are lacking for endocrine diseases - with the exception of type-I-diabetes. Moreover, tumor formation is very common, however, appropriate high-throughput applications reflecting the high heterogeneity and furthermore relevant 3D-structures in vitro are still widely lacking. Recently, we have initiated the development of standardized multidimensional models of a variety of endocrine cell/tissue sources in a new multiwell-format. Firstly, we confirmed common applicability for pancreatic pseudo-islets. Next, we translated applicability for spheroid establishment to adrenocortical cell lines as well as patient material to establish spheroids from malignant, but also benign adrenal tumors. We aimed furthermore at the development of bovine derived adrenal organoids and were able to establish steroidogenic active organoids containing both, cells of cortical and medullary origin. Overall, we hope to open new avenues for basic research, endocrine cancer and adrenal tissue-replacement-therapies as we demonstrate potential for innovative mechanistic insights and personalized medicine in endocrine (tumor)-biology.
Atlasing white matter and grey matter joint contributions to resting-state networks in the human brain
Authors: Nozais Victor , Forkel Stephanie J , Petit Laurent , Talozzi Lia , Corbetta Maurizio , Thiebaut de Schotten Michel , Joliot Marc
Published: January 2022

Over the past two decades, the study of resting-state functional magnetic resonance imaging has revealed that functional connectivity within and between networks are linked to cognitive states and pathologies. However, the white matter connections supporting connectivity remain only partially described. We developed a method to jointly map the white and grey matter contributing to each resting-state network. Using the Human Connectome Project, we generated an atlas of 30 resting-state networks. The method also allows highlighting the overlap between networks, which revealed that most of the brain’s white matter (89%) is shared between multiple networks, with 16% shared by at least 7 resting-state networks. These overlaps, especially the existence of regions shared by numerous networks, suggest that white matter lesions in these areas might strongly impact the correlations and the communication within resting-state networks. We provide an open-source software to explore the joint contribution of white and grey matter to RSNs and facilitate the study of the impact of white matter damage on RSNs. In a first clinical application of the software, we were able to link stroke patients and impacted resting-state networks, showing that their symptoms aligned well with the estimated functions of the networks.
A single-cell atlas reveals shared and distinct immune responses and metabolism during SARS-CoV-2 and HIV-1 infections
Authors: Pan Tony , Cao Guoshuai , Tang Erting , Zhao Yu , Penaloza-MacMaster Pablo , Fang Yun , Huang Jun
Published: January 2022

SARS-CoV-2 and HIV-1 are RNA viruses that have killed millions of people worldwide. Understanding the similarities and differences between these two infections is critical for understanding disease progression and for developing effective vaccines and therapies, particularly for 38 million HIV-1+individuals who are vulnerable to SARS-CoV-2 co-infection. Here, we utilized single-cell transcriptomics to perform a systematic comparison of 94,442 PBMCs from 7 COVID-19 and 9 HIV-1+patients in an integrated immune atlas, in which 27 different cell types were identified using an accurate consensus single-cell annotation method. While immune cells in both cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activities, and downregulated mitophagy. Our results elucidate transcriptional signatures associated with COVID-19 and HIV-1 that may reveal insights into fundamental disease biology and potential therapeutic targets to treat these viral infections.

Highlights

COVID-19 and HIV-1+patients show disease-specific inflammatory immune signatures

COVID-19 patients show more productive humoral responses than HIV-1+patients

SARS-CoV-2 elicits more enriched IFN-I signaling relative to HIV-I

Divergent, impaired metabolic programs distinguish SARS-CoV-2 and HIV-1 infections
Intellectual disability-associated disruption of O-GlcNAcylation impairs neuronal development and cognitive function in Drosophila
Authors: Fenckova Michaela , Muha Villo , Mariappa Daniel , Catinozzi Marica , Czajewski Ignacy , Blok Laura E.R. , Ferenbach Andrew T. , Storkebaum Erik , Schenck Annette , van Aalten Daan M.F.
Published: January 2022

O-GlcNAcylation is a reversible co-/post-translational modification involved in a multitude of cellular processes. The addition and removal of O-GlcNAc modification is controlled by two conserved enzymes, O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA). Mutations in OGT have recently been discovered to cause a novel Congenital Disorder of Glycosylation (OGT-CDG) that is characterized by intellectual disability. The mechanisms by which OGT-CDG mutations affect cognition remain unclear. We manipulated O-GlcNAc transferase and O-GlcNAc hydrolase activity in Drosophila and demonstrate an important role of O-GlcNAcylation in habituation learning and synaptic development at the larval neuromuscular junction. Introduction of patient-specific missense mutations into Drosophila O-GlcNAc transferase using CRISPR/Cas9 gene editing, leads to deficits in locomotor function and habituation learning. The habituation deficit can be corrected by blocking O-GlcNAc hydrolysis, indicating that OGT-CDG mutations affect cognitive function via reduced protein O-GlcNAcylation. This study establishes a critical role for O-GlcNAc cycling and disrupted O-GlcNAc transferase activity in cognitive dysfunction. These findings suggest that blocking O-GlcNAc hydrolysis is a potential treatment strategy for OGT-CDG.

Author summary

Attachment of single N-acetylglucosamine (GlcNAc) sugars to intracellular proteins has recently been linked to neurodevelopment and cognition. This link has been strengthened by discovery of O-GlcNAc transferase (OGT) missense mutations in intellectual disability. Most of these mutations lie outside the catalytic O-GlcNAc transferase domain and it is unclear how they affect cognitive function. Using the fruit fly Drosophila melanogaster as a model organism, we found that a balance in O-GlcNAc cycling is required for learning and neuronal development. Habituation, a fundamental form of learning, is affected in flies that carry patient-specific OGT mutations, and increasing O-GlcNAcylation genetically corrects the habituation deficit. Our work establishes a critical role for O-GlcNAc cycling in a cognition-relevant process, identifies defective O-GlcNAc transferase activity as a cause of intellectual disability, and proposes underlying mechanisms that can be further explored as treatment targets.
Cell type-specific aging clocks to quantify aging and rejuvenation in regenerative regions of the brain
Authors: Buckley Matthew T. , Sun Eric , George Benson M. , Liu Ling , Schaum Nicholas , Xu Lucy , Reyes Jaime M. , Goodell Margaret A. , Weissman Irving L. , Wyss-Coray Tony , Rando Thomas A. , Brunet Anne
Published: January 2022

Aging manifests as progressive dysfunction culminating in death. The diversity of cell types is a challenge to the precise quantification of aging and its reversal. Here we develop a suite of ‘aging clocks’ based on single cell transcriptomic data to characterize cell type-specific aging and rejuvenation strategies. The subventricular zone (SVZ) neurogenic region contains many cell types and provides an excellent system to study cell-level tissue aging and regeneration. We generated 21,458 single-cell transcriptomes from the neurogenic regions of 28 mice, tiling ages from young to old. With these data, we trained a suite of single cell-based regression models (aging clocks) to predict both chronological age (passage of time) and biological age (fitness, in this case the proliferative capacity of the neurogenic region). Both types of clocks perform well on independent cohorts of mice. Genes underlying the single cell-based aging clocks are mostly cell-type specific, but also include a few shared genes in the interferon and lipid metabolism pathways. We used these single cell-based aging clocks to measure transcriptomic rejuvenation, by generating single cell RNA-seq datasets of SVZ neurogenic regions for two interventions – heterochronic parabiosis (young blood) and exercise. Interestingly, the use of aging clocks reveals that both heterochronic parabiosis and exercise reverse transcriptomic aging in the niche, but in different ways across cell types and genes. This study represents the first development of high-resolution aging clocks from single cell transcriptomic data and demonstrates their application to quantify transcriptomic rejuvenation.
A novel structure-based approach for identification of vertebrate susceptibility to SARS-CoV-2: implications for future surveillance programmes
Authors: Kaushik Rahul , Kumar Naveen , Zhang Kam Y. J. , Srivastava Pratiksha , Bhatia Sandeep , Malik Yashpal Singh
Published: January 2022

Understanding the origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a highly debatable and unsolved challenge for the scientific communities across the world. A key to dissect the susceptibility profiles of animal species to SARS-CoV-2 is to understand how virus enters into the cells. The interaction of SARS-CoV-2 ligands (RBD on spike protein) with its host cell receptor, angiotensin-converting enzyme 2 (ACE2), is a critical determinant of host range and cross-species transmission. In this study, we developed and implemented a rigorous computational approach for predicting binding affinity between 299 ACE2 orthologs from diverse vertebrate species and the SARS-CoV-2 spike protein. The findings show that the spike protein of SARS-CoV-2 can bind to many vertebrate species carrying evolutionary divergent ACE2, implying a broad host range at the virus entry level, which may contribute to cross-species transmission and further viral evolution. Additionally, the present study facilitated the identification of genetic determinants that may differentiate susceptible from the resistant host species based on the conservation of ACE2-spike protein interacting residues in vertebrate host species known to facilitate SARS-CoV-2 infection; however, these genetic determinants warrant in vivo experimental confirmation. The molecular interactions associated with varied binding affinity of distinct ACE2 isoforms in a specific bat species were identified using protein structure analysis, implying the existence of diversified susceptibility of bat species to SARS-CoV-2. The findings from current study highlight the importance of intensive surveillance programs aimed at identifying susceptible hosts, particularly those with the potential to transmit zoonotic pathogens, in order to prevent future outbreaks.
SARS-CoV-2 Point Mutation and Deletion Spectra, and Their Association with Different Disease Outcome
Authors: Martínez-González Brenda , Soria María Eugenia , Vázquez-Sirvent Lucía , Ferrer-Orta Cristina , Lobo-Vega Rebeca , Mínguez Pablo , de la Fuente Lorena , Llorens Carlos , Soriano Beatriz , Ramos Ricardo , Cortón Marta , López-Rodríguez Rosario , García-Crespo Carlos , Gallego Isabel , de Ávila Ana Isabel , Gómez Jordi , Enjuanes Luis , Salar-Vidal Llanos , Esteban Jaime , Fernandez-Roblas Ricardo , Gadea Ignacio , Ayuso Carmen , Ruíz-Hornillos Javier , Verdaguer Nuria , Domingo Esteban , Perales Celia
Published: January 2022

Mutant spectra of RNA viruses are important to understand viral pathogenesis, and response to selective pressures. There is a need to characterize the complexity of mutant spectra in coronaviruses sampled from infected patients. In particular, the possible relationship between SARS-CoV-2 mutant spectrum complexity and disease associations has not been established. In the present study, we report an ultra-deep sequencing (UDS) analysis of the mutant spectrum of amplicons from the nsp12 (polymerase)- and spike (S)-coding regions of thirty nasopharyngeal isolates (diagnostic samples) of SARS-CoV-2 of the first COVID-19 pandemic wave (Madrid, Spain, April 2020) classified according to the severity of ensuing COVID-19. Low frequency mutations and deletions, counted relative to the consensus sequence of the corresponding isolate, were overwhelmingly abundant. We show that the average number of different point mutations, mutations per haplotype and several diversity indices was significantly higher in SARS-CoV-2 isolated from patients who developed mild disease than in those associated with moderate or severe disease (exitus). No such bias was observed with RNA deletions. Location of amino acid substitutions in the three dimensional structures of nsp12 (polymerase) and S suggest significant structural or functional effects. Thus, patients who develop mild symptoms may be a richer source of genetic variants of SARS-CoV-2 than patients with moderate or severe COVID-19.

IMPORTANCE

The study shows that mutant spectra of SARS-CoV-2 from diagnostic samples differ in point mutation abundance and complexity, and that significantly larger values were observed in virus from patients who developed mild COVID-19 symptoms. Mutant spectrum complexity is not a uniform trait among isolates. The nature and location of low frequency amino acid substitutions present in mutant spectra anticipate great potential for phenotypic diversification of SARS-CoV-2.
Efficient inactivation of African swine fever virus by a highly complexed iodine combined with compound organic acids
Authors: Qi Mengnan , Pan Li , Gao Ying , Li Miao , Wang Yanjin , Li Lian-Feng , Ji Chen , Sun Yuan , Qiu Hua-Ji
Published: January 2022

African swine fever (ASF) is a highly contagious disease with high morbidity and mortality caused by African swine fever virus (ASFV). Cleaning and disinfection remain one of the most effective biosecurity measures to prevent and control the spread of ASFV. In this study, we evaluated the inactivation effects of highly complexed iodine (HPCI) combined with compound organic acids (COAs) against ASFV under different conditions. The results showed that the inactivation rates of the disinfectants on the reporter ASFV increased in dose- and time-dependent manners, the best inactivation effects were obtained when the compatibility ratio of HPCI and COAs was 5:1 at 25°C. Furthermore, there were no significant differences by comparing the efficacy of HPCI combined with COAs (HPCI+COAs) in inactivating wild-type ASFV and the reporter ASFV (P > 0.05). ASFV of 104.0 TCID50/mL was completely inactivated by 0.13% HPCI (0.0065% effective iodine), 0.06% COAs or 0.13% HPCI+COAs (approximately 0.0054% effective iodine), respectively, while 106.0 TCID50/mL ASFV was completely inactivated by 1.00% HPCI (0.05% effective iodine), 0.50% COAs or 1.00% HPCI+COAs (0.042% effective iodine), respectively. Therefore, HPCI+COAs had synergistic effects to inactivate ASFV. This study demonstrated that HPCI+COAs could rapidly and efficiently inactivate ASFV and represent an effective compound disinfectant for the control of ASF.

IMPORTANCE

African swine fever (ASF) is a highly contagious disease with high morbidity and mortality caused by African swine fever virus (ASFV). Due to the lack of commercial vaccines and treatment available for ASF, effective disinfectants and the proper use of them are extremely essential to inactivate ASFV. The significance of this research is in searching for an ideal disinfectant that not only has the advantages of low toxicity and non-pollution but also can inactivate ASFV rapidly and efficiently. In this study, we proved that HPCI+COAs not only exhibited low cytotoxicity, but also could completely inactivate ASFV within 5 min at 4°C, 25°C and 37°C. In addition, HPCI+COAs had synergistic effects on inactivated ASFV. Thus, HPCI +COAs could be used as an effective disinfectant for the control of ASF.
COVID-19 vaccination breakthrough infections in a real-world setting: Using community reporters to evaluate vaccine effectiveness
Authors: Reynolds Matthew W , Xie Yiqiong , Knuth Kendall B , Mack Christina D , Brinkley Emma , Toovey Stephen , Dreyer Nancy A
Published: January 2022

Background

COVID-19 has highlighted the need for new methods of pharmacovigilance. Here we use community volunteers to obtain systematic information on vaccine effectiveness and the nature and severity of breakthrough infections.

Methods

Between December 15, 2020 to September 16, 2021, 10,412 unpaid community-based participants reported the following information to an on-line registry: COVID-19 test results, vaccination (Pfizer, Moderna, or Johnson & Johnson), COVID-19 symptoms and perceived severity using a 4-point scale. COVID-19 infections were described for those who were 1) fully vaccinated, 2) partially vaccinated (received first of two dose vaccines or were <14 days post-final dose), or 3) unvaccinated.

Results

Of 8,554 who were vaccinated, COVID-19 infections were reported by 74 (1.0%) of those who were fully vaccinated and 198 (2.3%) of those who were partially vaccinated. Among the 74 participants who reported a breakthrough infection after full vaccination, the median time to reported positive test result was 104.5 days (Interquartile range: 77-135 days), with no difference among vaccine manufactures. One quarter (25.7%) of breakthrough infections in the fully vaccinated cases were asymptomatic. More than 97% of fully vaccinated participants reported no moderate/severe symptoms compared to 89.3% of the unvaccinated cases; and only 1.4% of fully vaccinated participants reported experiencing at least 3 moderate to severe symptoms compared to 7.8% in the unvaccinated.

Conclusion

Person-generated health data, also referred to as patient-reported outcomes, is a useful resource for quantifying breakthrough infections and their severity, showing here that fully vaccinated participants report no or very mild COVID-19 symptoms.

Trial registration

Clinicaltrials.govNCT04368065, EU PAS Register EUPAS36240
How do growth and nutrition explain social inequalities in lung function in children with cystic fibrosis? A longitudinal mediation analysis using interventional disparity effects with time-varying mediators and intermediate confounders
Authors: Schlüter Daniela K. , Keogh Ruth H. , Daniel Rhian M. , Agbla Schadrac C. , Taylor-Robinson David
Published: January 2022

Background

Deprivation is associated with poorer growth, worse lung function and shorter life expectancy in children with cystic fibrosis (CF). While early growth is associated with lung function when first measured at around age 6, it is unclear whether improving early growth in the most disadvantaged children would reduce inequalities in lung function.

Methods

We used data from children born 2000-2010 and followed up to 2016 in the UK CF Registry. To estimate the association between deprivation and lung function at around age six, and the causal contribution of early weight trajectories, we extended the mediation analysis approach based on interventional disparity effects to the setting of a longitudinally measured mediator. We adjusted for baseline confounding by sex, birthyear and genotype and accounted for time-varying intermediate confounding by lung infection.

Results

853 children were included in the study, including 165 and 172 children from the least and most deprived population quintiles, respectively. The average difference in lung function between the least and most deprived quintile of children, was 4.51 percent of predicted forced expiratory volume in one second (95% CI: 1.08 - 7.93). We estimated this would be reduced to 3.97 percentage points (95% CI: 0.57 – 7.38) if early weight trajectories in the most deprived children were shifted to the distribution observed in the least disadvantaged children.

Conclusion

Socio-economic conditions are strongly associated with lung function for children with CF which we estimated would only be marginally reduced if early weight trajectories could be improved for the most disadvantaged children.
Smoking in social housing among adults in England, 2015-2020: a nationally representative survey
Authors: Jackson Sarah E. , Cheeseman Hazel , Arnott Deborah , Titmarsh Robbie , Brown Jamie
Published: January 2022

Objectives

To analyse associations between living in social housing and smoking in England and evaluate progress toward reducing disparities in smoking prevalence among residents of social housing compared with other housing types.

Design

Nationally-representative, cross-sectional survey between January 2015 and February 2020.

Setting

England.

Participants

105,562 adults (≥16y).

Primary and secondary outcome measures

Linear and logistic regression were used to analyse associations between living in social housing (vs. other housing types) and smoking status, cigarettes per day, time to first cigarette, exposure to smoking by others, motivation to stop smoking, quit attempts, and use of cessation support. Analyses adjusted for sex, age, social grade, region, and survey year.

Results

Adults living in social housing had twice the odds of being a smoker (ORadj=2.17, 95%CI 2.08- 2.27), and the decline in smoking prevalence between 2015 and 2020 was less pronounced in this high-risk group (−7%; ORadj=0.98, 95%CI 0.96-1.01) than among adults living in other housing types (− 24%; ORadj=0.95, 95%CI 0.94-0.96; housing tenure*survey year interaction p=0.020). Smokers living in social housing were more addicted than those in other housing (smoking within 30 minutes of waking: ORadj=1.50, 95%CI 1.39-1.61), but were no less motivated to stop smoking (ORadj=1.06, 95%CI 0.96-1.17) and had higher odds of having made a serious attempt to quit in the past year (ORadj=1.16, 95%CI 1.07-1.25). Among smokers who had tried to quit, those living in social housing had higher odds of using evidence-based cessation support (ORadj=1.22, 95%CI 1.07-1.39) but lower odds of remaining abstinent (ORadj=0.63, 95%CI 0.52-0.76).

Conclusions

There remain stark inequalities in smoking and quitting behaviour by housing tenure in England, with declines in prevalence stalling between 2015 and 2020 despite progress in the rest of the population. In the absence of targeted interventions to boost quitting among social housing residents, inequalities in health are likely to worsen.

Strengths and limitations of this study

A major strength of this study was the large sample, which was representative of adults living in England.

Another strength was the broad range of smoking outcomes assessed, offering a detailed view of smoking behaviour among people living in social housing compared with those living in other housing types.

The main limitation was that all outcomes were self-reported, introducing scope for bias.
The incidence and mortality of COVID-19 related TB disease in Sub-Saharan Africa: A systematic review and meta-analysis
Authors: Tamuzi Jacques L , Lulendo Gomer , Mbuesse Patrick , Nyasulu Peter S.
Published: January 2022

Background

Coronavirus disease 2019 (COVID-19) is also associated with other co-morbidities in people who have previously or currently have pulmonary tuberculosis (PTB). PTB is a risk factor for COVID-19, both in terms of severity and mortality, regardless of HIV status. However, there is less information available on COVID-19 and PTB in terms of incidence and mortality rates in Sub-Saharan Africa (SSA), a high-burden TB region. This systematic review provided a data synthesis of available evidence on COVID-19/PTB incidence and case fatality rates, as well as mortality rates found in clinical and post-mortem COVID-19/PTB diagnostics in SSA.

Methods

We conducted an electronic search in the PubMed, Medline, Google Scholar, Medrxix, and COVID-19 Global literature on coronavirus disease databases for studies involving COVID-19 and PTB in Sub-Saharan Africa. The primary outcomes were the incidence proportion of people with COVID-19 who had current or previous PTB, as well as the case fatality rate associated with COVID-19/PTB. Based on methodological similarities in the included random effect model studies, the combination method was developed using Stata version 16 and Prometa 3 software. We also performed sensitivity analysis and meta-regression.

Results

From the 548 references extracted by the literature search, 25 studies were selected and included in the meta-analysis with a total of 191, 250 COVID-19 infected patients and 11, 480 COVID-19 deaths. The pooled COVID-19/PTB incidence was 3% [2%-5%] and a case fatality rate of 13% [4%-23%]. The pooled estimates for case fatality rate among COVID-19/PTB were 7% [1%-12%] for clinical PTB diagnostic and 25% [3%-47%] for post-mortem PTB diagnostic. Previous TB had the highest incidence and fatality rates with 46 [19-73] per 1, 000 population and 8% [3%-19%], respectively. Meta-regression model including the effect sizes and cumulative COVID-19 cases (P= 0.032), HIV prevalence (P= 0.041), and TB incidence (P= 0.002) to explain high heterogeneity between studies.

Conclusion

To summarize, the incidence of TB associated with COVID-19 is higher in SSA, as are the case fatality rates, when compared to the rest of the world. However, because the post-mortem TB diagnostic was higher, COVID-19 associated with TB may have been underreported in studies conducted in SSA. To confirm COVID-19/TB incidence and case fatality rates in SSA, large-scale cohort studies that adequately clear tools on previous and/or current TB diagnostic tools are required.

Review registration

PROSPERO (CRD42021233387)
Functional status, mood state, and physical activity among women with post-acute COVID-19 syndrome
Authors: Carter Stephen J. , Baranauskas Marissa N. , Raglin John S. , Pescosolido Bernice A. , Perry Brea L.
Published: January 2022

Objectives

While organ-specific pathophysiology has been well-described in SARS-CoV-2 infection, less is known about the attendant effects on functional status, mood state and leisure-time physical activity (PA) in post-acute COVID-19 syndrome.

Methods

A case-control design was employed to recruit 32 women (n = 17 SARS-CoV-2; n = 15 controls) matched on age (54 ± 12 years), body mass index (27 ± 6 kg/m2), smoking status, and history of cardiopulmonary disease. Participants completed a series of assessments including the Modified Pulmonary Functional Status and Dyspnea Questionnaire (PFSDQ-M), Profile of Mood States (POMS), and Godin-Shephard Leisure-Time PA.

Results

SARS-CoV-2 participants exhibited poorer functional status (p = 0.008) and reduced leisure-time PA (p = 0.004) compared to controls. Significant between-group differences were also detected for the POMS total mood disturbance with sub-scale analyses revealing elevated tension, confusion, and lower vigor among SARS-CoV-2 participants (all p-values < 0.05). The number of SARS-CoV-2 symptoms (e.g., loss of taste / smell, muscle aches etc.) were associated (r = 0.620, p = 0.008) with confusion.

Conclusion

The sequela of persistent SARS-CoV-2 symptoms elicit clear disturbances in functional status, mood state, and leisure-time PA among women with post-acute COVID-19 syndrome.
Strand-switching mechanism of Pif1 helicase induced by its collision with a G-quadruplex embedded in dsDNA
Authors: Valle-Orero Jessica , Rieu Martin , Tran Phong Lan Thao , Joubert Alexandra , Allemand Jean-François , Croquette Vincent , Boulé Jean-Baptiste
Published: January 2022

G-rich sequences found at multiple sites throughout all genomes may form secondary structures called G-quadruplexes (G4), which act as roadblocks for molecular motors. Among the enzymes thought to process these structures, the Pif1 DNA helicase is considered as an archetypical G4-resolvase and its absence has been linked to G4-related genomic instabilities in yeast. Here we developed a single-molecule assay to observe Pif1 opening a DNA duplex and resolving the G4 in real time. In support of former enzymological studies, we show that the helicase reduces the lifetime of G4 from hours to seconds. However, we observe that in presence of a G4, Pif1 exhibits a strong strand switching behavior, which can lead to Pif1 escaping G4 resolution, depending on the structural context surrounding the substrate. This behavior is also detected in presence of other roadblocks (LNA or RNA). We propose that the efficiency of Pif1 to remove a roadblock (G4 or other) is affected by its strand switching behavior and depends on the context surrounding the obstacle. We discuss how this switching behavior may explain several aspects of Pif1 substrate preference and affect its activity as a G4 resolvase in vivo.
A thalamo-preoptic pathway promoting social touch
Authors: Keller Dávid , Láng Tamás , Cservenák Melinda , Puska Gina , Barna János , Csillag Veronika , Farkas Imre , Zelena Dóra , Dóra Fanni , Barteczko Lara , Usdin Ted B. , Palkovits Miklós , Hasan Mazahir T. , Grinevich Valery , Dobolyi Arpád
Published: January 2022

Social touch is an important form of communication, it is still unknown how it is processed. Here, we discovered a functional role for a neuronal pathway projecting from the posterior intralaminar thalamic nucleus (PIL) to the medial preoptic area (MPOA) in controlling social contact. Neurons in the PIL and the MPOA were activated by physical contact between female rodents and also by chemogenetic stimulation of PIL neurons. Chemogenetic stimulation of PIL neurons tagged by social contact experience increased direct physical interactions between familiar female rats without affecting other forms of social behavior. Furthermore, selective stimulation of the PIL-MPOA pathway, and the local activation of PIL terminals within the MPOA, elevated direct social contact between the animals suggesting the role of pathway-specific activated cell assemblies. Neurons projecting from the PIL to the MPOA contain the neuropeptide parathyroid hormone 2 (PTH2). The expression of the peptide was induced by social housing, the presence of PTH2 receptor was identified in MPOA neurons, and local injection of PTH2 increased the firing rate of identified preoptic area GABAergic neurons via the PTH2 receptor suggesting that PTH2 acts as a neurotransmitter in the PIL-MPOA pathway. We also found a homologous PIL to MPOA neuronal pathway in the human brain. Altogether, we discovered a direct thalamo-preoptic pathway, which bypasses the cerebral cortex and controls social touch. This pathway originates in neurons expressing PTH2, a neuropeptide recently shown in fish to respond to the social environment. These observations provide evidence for common evolutionary-conserved PTH2-containing social-touch specific engram circuits.
Cross-kingdom analysis of microbial communities in Cystic Fibrosis and Bronchiectasis
Authors: Cuthbertson L. , Ish-Horowicz J. , Felton I.C. , James P. , Turek E. , Cox M.J. , Loebinger M.R. , Simmonds N.J. , Filippi S. , Moffatt M.F. , Cookson W.O.C.
Published: January 2022

Background

Cystic fibrosis (CF) and non-CF bronchiectasis (BX) are characterised by severe chronic infections. Fungal and bacterial components of infection are both recognized. Little however is known about how fungal and bacterial organisms interact and whether these interactions impact on disease outcomes.

Methods

Quantitative PCR and next-generation sequencing of ITS2 and 16S rRNA gene was carried out on 107 patients with CF or BX with clinically defined fungal infection status for all patients. The relationship between fungal and bacterial community composition was extensively explored using: random forest modelling, correlation network analysis, multi-omics factor analysis, and sample-wise clustering, to understand associations both within and between the microbial communities and their relationship to respiratory disease.

Results

Random forest modelling demonstrated distinct fungal and bacterial communities within CF and BX patients. The inclusion of both kingdoms in the models did not improve discrimination between the two diseases. Within the CF patients, bacterial community composition was independent of clinical fungal disease status. Bacterial and fungal communities did not relate to the presence of CF pulmonary exacerbations (CFPE). Correlation network analysis found intra-kingdom interactions were predominant in the data. Multi-omics factor analysis (MOFA) revealed latent factors corresponding to single kingdoms. Thus, in the bacterial community we identified two distinct clusters characterised by the presence or absence ofPseudomonas-domination. This was independent of fungal community which was characterised by a second set of independent clusters dominated bySaccharomycetes.

Conclusions

In this study we were unable to detect clear evidence of clinically significant inter-kingdom interactions between the bacterial and fungal communities. While further work is required to fully understand microbial interaction within the lung, our data suggests that interkingdom interactions may not be the primary driver of patient outcomes, particularly in the context of fungal infection.
Evaluation of the anti-tumor activities of Sulfonylurea Derivatives
Authors: Lu Sen , Guo Chenchen , Wu Lei , Zheng Zhanying , Hua Xuewen , Wei Wei , Zhang Wenqin , Zhou Shaa , Li Ruo , Zhou Sha
Published: January 2022

This study prepared 25 sulfonylurea compounds to evaluate anti-tumor activity. Through experimental investigations in MDA-MB-231 and MCF-7, i.e., cell lines of breast carcinoma of human, we have concluded that some compounds can significantly suppress breast carcinoma cells from growing and proliferating. Moreover, the compound M’s inhibitory effect on cells of breast carcinoma is concentration-dependent under a certain treatment time; and the inhibitory effect of the compound M on breast carcinoma cells is time-dependent under a certain concentration. In addition, we also found that the compound M can effectively suppress cells of breast carcinoma from migration and independent survival. The results can show the prospect of research and development of new breast carcinoma treatment drug.
Phylogenetic and protein prediction analysis reveals the taxonomically diverse distribution of virulence factors in the Bacillus cereus group
Authors: Zhang Ming , Liu Jun , Yin Zhenzhen , Zhang Li
Published: January 2022

Bacillus cereus is a food contaminant with widely varying enterotoxic potential of its virulence proteins. In this article, phylogenetic analysis of the whole-genome amino acid sequences of 41 strains, evolutionary distance calculation of the amino acid sequences of the virulence genes, and functional and structural prediction of the virulence proteins were performed to reveal the taxonomically diverse distribution of virulence factors. The genome evolution of the strains showed a clustering trend based on the coding virulence genes. The strains of B. cereus have evolved into non-toxic risk and toxic risk clusters with medium-high- and medium-low-risk clusters. The distances of evolutionary transfer relative to housekeeping genes of incomplete virulence genes were greater than those of complete virulence genes, and the distance values of HblACD were higher than those of nheABC and CytK among the complete virulence genes. Cytoplasmic localization was impossible for all the virulence proteins, and NheB, NheC, Hbl-B, and Hbl-L1 were extracellular according to predictive analysis. Nhe and Hbl proteins except CytK had similar spatial structures. The predicted structures of Nhe and Hbl mainly showed ‘head’ and ‘tail’ domains. The ‘head’ of NheA and Hbl-B, including two α-helices separated by β-tongue strands, might play a special role in Nhe trimers and Hbl trimers, respectively. The ‘cap’ of CytK, which includes two ‘latches’ with many β-sheets, formed a β-barrel structure with pores, and a ‘rim’ balanced the structure. The evolution of B. cereus strains showed a clustering tendency based on the coding virulence genes, and the complete virulence-gene operon combination had higher relative genetic stability. The beta-tongue or latch associated with β-sheet folding might play an important role in the binding of virulence structures and pore-forming toxins in B. cereus.
Performance evaluation of three DNA sample tracking tools in a whole exome sequencing workflow
Authors: Wils Gertjan , Helsmoortel Céline , Volders Pieter-Jan , Vereecke Inge , Milazzo Mauro , Vandesompele Jo , Coppieters Frauke , De Leeneer Kim , Lefever Steve
Published: January 2022

Introduction

Next-generation sequencing applications are becoming indispensable for clinical diagnostics. These experiments require numerous wet and dry lab steps, each one increasing the probability of a sample swap or contamination. Therefore, an identity confirmation at the end of the process is recommended to ensure the right data is used for each patient.

Methods

We tested three commercially available, SNP based sample tracking kits in a diagnostic workflow to evaluate their ease of use and performance. The coverage uniformity, on-target specificity, sample identification and genotyping performance were determined to assess the reliability and the cost-effectiveness of each kit.

Results and discussion

Hands-on time and manual steps are almost identical for the kits from pxlence and Nimagen. The Swift kit has an extra purification step, making it the longest and most demanding protocol. Furthermore, the Swift kit failed to correctly genotype 26 out of the 46 samples. The Nimagen kit identified all but one sample and the pxlence kit unambiguously identified all samples, making it the most reliable and robust kit of this evaluation. The Nimagen kit showed poor on-target mapping rates, resulting in deeper sequencing needs and higher sequencing costs compared to the other two kits. Our conclusion is that the Human Sample ID kit from pxlence is the most cost-effective of the three tested tools for DNA sample tracking and identification.

Key points

Kits from pxlence and Nimagen are easy to use.

Unambiguous identification of all samples possible with the pxlence kit.

Only 20 out of 46 samples were correctly identified with the Swift kit.

Poor on-target rates for the Nimagen kit results in higher sequencing costs.
SARS-CoV-2 Triggers Complement Activation through Interactions with Heparan Sulfate
Authors: Lo Martin W. , Amarilla Alberto A. , Lee John D. , Albornoz Eduardo A. , Modhiran Naphak , Clark Richard J. , Ferro Vito , Chhabra Mohit , Khromykh Alexander A. , Watterson Daniel , Woodruff Trent M.
Published: January 2022

The complement system has been heavily implicated in severe COVID-19 with clinical studies revealing widespread gene induction, deposition, and activation. However, the mechanism by which complement is activated in this disease remains incompletely understood. Herein we examined the relationship between SARS-CoV-2 and complement by inoculating the virus in lepirudin-anticoagulated human blood. This caused progressive C5a production after 30 minutes and 24 hours, which was blocked entirely by inhibitors for factor B, C3, C5, and heparan sulfate. However, this phenomenon could not be replicated in cell-free plasma, highlighting the requirement for cell surface deposition of complement and interactions with heparan sulfate. Additional functional analysis revealed that complement-dependent granulocyte and monocyte activation was delayed. Indeed, C5aR1 internalisation and CD11b upregulation on these cells only occurred after 24 hours. Thus, SARS-CoV-2 is a non-canonical complement activator that triggers the alternative pathway through interactions with heparan sulfate.
Microscopic and ultramicroscopic anatomical characteristics of root nodules in Podocarpus macrophyllus during development
Authors: Zhu Li-Qiong , Chen Hui-Xin , Zhao Li-Jun , Jiang Wei-Xin
Published: January 2022

To understand the morphological and structural characteristics of root nodules in Podocarpus macrophyllus and their development, this study prepared P. macrophyllus root nodule samples at the young, mature, and senescent stages. Optical microscopy and transmission electron microscopy (SEM) revealed that new nodules can be formed on roots and senescent nodules; new nodules formed on the roots are nearly spherical and have an internal structure similar to finite nodules; new nodules on senescent nodules are formed by extension and differentiation of the vascular cylinder of the original nodules; and these new nodules are nested at the base of the original nodules, which create growth space for new nodules by dissociating the cortical tissue; clusters of nodules are formed after extensive accumulation, and the growth pattern is similar to that of infinite nodules; the symbiotic bacteria of P. macrophyllus root nodules mainly invade from the epidermal intercellular space of the roots and migrate along the intercellular space of the nodule cortex; infected nodule cortex cells have a well-developed inner membrane system and enlarged and loose nuclei; and unique Frankia vesicles, and rhizobia cysts, and bacteriophages can all develop. Compared with common leguminous and nonleguminous plant nodules, P. macrophyllus root nodules are more complex in morphology, structure and composition. From the perspective of plant system evolution, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as P. macrophyllus. The conclusions of this study can provide a theoretical basis for the developmental biology of P. macrophyllus root nodules and the evolutionary pattern of plant symbionts.

Highlights

We discuss from the perspective of cell developmental biology, the rhizobium nodules in leguminous angiosperms and Frankia nodules in nonleguminous angiosperms are most likely two branches derived from the nodules in gymnosperms, such as Podocarpus macrophyllus.