bluuebunny/crossref_metadata_2025 huggingface dataset:
Spiritual well-being and its association with health-related quality of life in primary brain tumor patients
Authors: Randazzo Dina M , McSherry Frances , Herndon James E , Affronti Mary L , Lipp Eric S , Miller Elizabeth S , Woodring Sarah , Healy Patrick , Jackman Jennifer , Crouch Brian , Desjardins Annick , Ashley David M , Friedman Henry S , Peters Katherine B
Published: February 2021

Background

Spirituality can impact patients’ attitudes and decisions about treatment and end-of-life care when coping with cancer. Previous studies documented health-related quality of life (HRQoL) and spiritual well-being (SWB) as positively correlated within a general cancer patient population, but little is known about their association in the primary brain tumor population. We sought to measure SWB in primary brain tumor patients and evaluate whether it was associated with HRQoL.

Methods

Six-hundred and six patients treated at The Preston Robert Tisch Brain Tumor Center at Duke between December 16, 2013 and February 28, 2014 with data in the PRoGREss registry are included in this retrospective analysis. Each patient completed the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-Sp-12) and -Fatigue (FACIT-F), and the Functional Assessment of Cancer Therapy-General and -Brain (FACT-G and FACT-Br).

Results

Mean age was 49.1 years (SD = 13.5 years), male (N = 328, 54.1%), married (N = 404, 66.7%), at least college-educated (N = 381, 62.9%), and diagnosed with a high-grade glioma (N = 412, 68.0%). Multiple regression analyses were performed on both the FACT-G and the FACT-Br using the FACIT-Sp-12 sub-scales of Meaning/Peace and Faith, FACIT-F, belief in God or a higher power, prayer, gender, tumor grade, and Karnofsky Performance Status (KPS) as predictors. We found that greater SWB (measured by FACIT-Sp-12) was associated with better HRQoL (measured by FACT-G and FACT-Br; p < .0001).

Conclusion

The association between reported SWB and reported improved HRQoL emphasizes the importance of spirituality in primary brain tumor patients, suggesting SWB must be considered in strategies to improve HRQoL.
Take-home and digital Lenten filter ashes for Ash Wednesday: creative ritual practices of faith during COVID-19 pandemic
Authors: Deguma Jabin J , Capuno Reylan G , Deguma Melona C , Igot Vicente J , Lumayag Charisma G
Published: February 2021

Before the coronavirus disease 2019 (COVID-19) pandemic, previous research cautioned that complex and meaningful quotidian rituals involving intimate touch need re-evaluation as these pose a hygienic concern in pandemic culture. Faith-based practices entail human-to-human contact that could inevitably cause the virus infection contagion if not appropriately addressed. In a World Health Organization document, the crucial role of inter-faith collaboration and sharing of best practices to combat the spread of the virus are encouraged. In this correspondence, we assert that taking home ashes and launching digital Lenten ashes filter are non-traditional yet creative ways for the Catholic Church to perform the ritual practice in celebrating Ash Wednesday. We argued that such creative ritual practices changed the landscape of faith-based practices and implied trans-local participation of the Catholic community as witnesses of faith while upkeeping public health.
The impact of the COVID-19 pandemic on people with rheumatic and musculoskeletal diseases: insights from patient-generated data on social media
Authors: Reuter Katja , Deodhar Atul , Makri Souzi , Zimmer Michael , Berenbaum Francis , Nikiphorou Elena
Published: February 2021

Objectives

During the COVID-19 pandemic, much communication occurred online, through social media. This study aimed to provide patient perspective data on how the COVID-19 pandemic impacted people with rheumatic and musculoskeletal diseases (RMDs), using Twitter-based patient-generated health data (PGHD).

Methods

A convenience sample of Twitter messages in English posted by people with RMDs was extracted between 1 March and 12 July 2020 and examined using thematic analysis. Included were Twitter messages that mentioned keywords and hashtags related to both COVID-19 (or SARS-CoV-2) and select RMDs. The RMDs monitored included inflammatory-driven (joint) conditions (ankylosing spondylitis, RA, PsA, lupus/SLE and gout).

Results

The analysis included 569 tweets by 375 Twitter users with RMDs across several countries. Eight themes emerged regarding the impact of the COVID-19 pandemic on people with RMDs: (i) lack of understanding of SARS-CoV-2/COVID-19; (ii) critical changes in health behaviour; (iii) challenges in healthcare practice and communication with healthcare professionals; (iv) difficulties with access to medical care; (v) negative impact on physical and mental health, coping strategies; (vi) issues around work participation; (vii) negative effects of the media; and (viii) awareness-raising.

Conclusion

The findings show that Twitter serves as a real-time data source to understand the impact of the COVID-19 pandemic on people with RMDs. The platform provided ‘early signals’ of potentially critical health behaviour changes. Future epidemics might benefit from the real-time use of Twitter-based PGHD to identify emerging health needs, facilitate communication and inform clinical practice decisions.
Palmar erythema and palmar papules as predictors for dermatomyositis-related acute/subacute interstitial lung disease: a retrospective study
Authors: Lu Jinghao , Liu Chaofan , Zhou Xing , Tang Jiaxuan , Liu Shiying , Tang Min , Li Ming , Zhu Lubing
Published: February 2021

Objectives

DM-related acute/subacute interstitial lung disease (A/S-ILD) remains a big therapeutic challenge due to its insidious onset and rapid development. In the present study, we aimed to investigate the association between clinical features of DM and ILD.

Methods

We retrospectively assessed skin manifestations, muscle damage, laboratory tests, concurrent ILD and malignancy in 207 patients with DM and analysed the high-risk factors for ILD.

Results

In the 207 DM patients, 153 patients had ILD, in which 131 had chronic ILD (CILD) and 22 had A/S-ILD. The proportions of mechanic’s hands, palmar papules and muscle weakness, as well as anti-melanoma differentiation-associated gene 5 (MDA5) antibody and lactic dehydrogenase (LDH), alanine aminotransferase (ALT) and ferritin in the ILD group were significantly higher compared with the non-ILD group. The onset age over 56 years, mechanic’s hands and muscle weakness were independent predictive factors for ILD. The proportions of palmar papules, palmar erythema, anti-MDA5 antibody, ALT, aspartate aminotransferase (AST), LDH and ESR in the A/S-ILD group were higher compared with the CILD group. Palmar erythema and palmar papules were independent predictive factors for A/S-ILD. Palmar papules were positively correlated with anti-MDA5 antibody.

Conclusion

The onset age over 56 years, mechanic’s hands or muscle weakness predicted the incidence of DM-related ILD, while palmar erythema or palmar papules could predict potential DM-related A/S-ILD.
Is Perception Reality? Using Person-in-Context Simulation to Promote Empathic Understanding of Dementia Among Nurse Practitioner Students
Authors: Harrington Candace C. , Neil Janice A. , Hardin Sonya R. , Roberson Donna W.
Published: February 2021

This one-group nonexperimental pretest/posttest repeated-measures design plus interpretative phenomenological analysis explored nurse practitioner students’ perceptions of dementia using virtual simulation. Perceptions of dementia and its associated challenges differed after the simulation. A critical theme that emerged was “developing empathic understanding”; the two subthemes were “mirroring dementia behaviors” and “provoking emotions.” Virtual dementia simulation is an inexpensive, low-fidelity strategy to challenge assumptions and preconceived belief systems about dementia. Person-in-context experiential learning is valuable in nurse practitioner education for facilitating empathic understanding. Further research is needed to explore the correlation between empathic understanding and altruistic helping behaviors in professional practice.
Role of the kisspeptin/KISS1 receptor system in the testicular development of mice
Authors: Chiang Chi-Ming , Chiu Hsin-Yi , Jong De-Shien , Wu Leang-Shin , Lee Yue-Jia , Chiu Chih-Hsien
Published: February 2021

Background:

Kisspeptin and its receptor KISS1R have been found to be essential regulators of reproductive function. Previous data have revealed the presence of Kiss1 and Kiss1r mRNAs in the hypothalamus and the testis of humans and rodents. However, the precise location and possible physiological role of the kisspeptin/KISS1R system in the testis remain ambiguous.

Methods:

We first produced an anti-KISS1R immunoglobulin Y antibody for KISS1R identification. To detect the exact sites of KISS1R and kisspeptin expression in the testis, we conducted immunohistochemistry assays on sections of testes. We used real-time polymerase chain reactions to identify Kiss1r in mice and to determine the expression levels of testicular genes. Finally, to verify the upstream regulation on the Kisspeptin/KISS1 receptor system, we treated primary mouse Leydig cells and MA-10 cells with luteinizing hormone (LH) and Br-cAMP, respectively, and examined Kiss1 and Kiss1r mRNA expression.

Results:

Immunohistochemistry assays revealed that kisspeptin was expressed in Leydig cells and KISS1R was localized in the seminiferous tubules. With real-time polymerase chain reactions, we found Kiss1r mRNA was constitutively expressed in the mouse testis from birth until the postnatal fourth week. Furthermore, mRNA expression of Kiss1 was synchronized with that of Insl3 and Cyp19a. However, the expression of the LH receptor-encoding gene increased 1 week earlier than did Kiss1 expression. This indicated that the kisspeptin/KISS1R system in the testis may be controlled by LH and cAMP signaling pathways. Finally, we confirmed that Kiss1 mRNA expression was increased in both LH-treated primary Leydig cells and Br-cAMP-treated MA-10 cells (p < 0.05). On the other hand, cotreatment of both cell lines with Br-cAMP and a protein kinase A inhibitor RP-cAMP significantly suppressed 50% of Br-cAMP-induced Kiss1 expression (p < 0.05).

Conclusion:

We discovered that Kiss1 expression in mouse Leydig cells was induced by LH through the cAMP/PKA pathway. Based on the presence of kisspeptin receptors on spermatids, we inferred that kisspeptin- and development-related factors have synergistic effects on spermatogenesis. Nevertheless, more studies are required to elaborate the role of the kisspeptin/KISS1R system in testicular development.
Paying for Sex Among Males and Females: A Cross-Sectional Survey in Melbourne, Australia
Authors: Chow Eric P.F. , Hocking Jane S. , Bradshaw Catriona S. , Phillips Tiffany R. , Tabesh Marjan , Donovan Basil , Maddaford Kate , Chen Marcus Y. , Fairley Christopher K.
Published: February 2021

Background

Most research focuses on individual selling sex but very few on paying for sex. This study aimed to determine the proportion of males and females who paid for sex and associated factors.

Methods

We conducted a short survey at the Melbourne Sexual Health Centre between March and April 2019, which included a question on whether they had paid for sex in the past 3 months. The proportion of individuals who had paid for sex was calculated by sex and sexual orientation. Univariable and multivariable logistic regression models were conducted to identify individual's factors (e.g., demographics, sexual orientation, and HIV/sexually transmitted infection [STI] positivity) associated with paying for sex in the past 3 months.

Results

The proportion who reported paying for sex in the past 3 months was 12.2% (42/345) among heterosexual males, followed by 6.4% (23/357) among men who have sex with men (MSM) and 0.2% (1/430) among females. HIV status, preexposure prophylaxis use, and sexual orientation were not associated with paying for sex among MSM. No MSM living with HIV reported paying for sex in the past 3 months. There was a significant association between paying for sex and gonorrhea (odds ratio, 2.84; 95% confidence interval, 1.05–7.71; P = 0.041) but not HIV, syphilis, and chlamydia among MSM. HIV/STI was not associated with paying for sex among heterosexual males.

Conclusions

Paying for sex was more commonly reported among heterosexual males, followed by MSM. Females were very unlikely to pay for sex. There was a limited association between HIV/STI diagnosis and paying for sex among males.
Comparison of Associations Between Glucocorticoids Treatment and Mortality in COVID-19 Patients and SARS Patients: A Systematic Review and Meta-Analysis
Authors: Li Jianbo , Liao Xuelian , Zhou Yue , Wang Luping , Yang Hang , Zhang Wei , Zhang Zhongwei , Kang Yan
Published: February 2021

Background:

The response to glucocorticoids treatment may be different between coronavirus disease 2019 (Covid-19) and severe acute respiratory syndrome (SARS).

Methods:

In this systematic review and meta-analysis, we searched studies on Medline, Embase, EBSCO, ScienceDirect, Web of Science, Cochrane Library, ClinicalTrials.gov, International Clinical Trials Registry Platform from 2002 to October 7, 2020. We used fixed-effects and random-effects models to compute the risk ratio of death in the group receiving glucocorticoids treatment and the control group for COVID-19 and SARS, respectively.

Results:

Ten trials and 71 observational studies, with a total of 45,935 patients, were identified. Glucocorticoids treatment was associated with decreased all-cause mortality both in COVID-19 (risk ratio, 0.88; 95% confidence interval, 0.82–0.94; I2 = 26%) and SARS (0.48; 0.29–0.79; 10%), based on high-quality evidence, as well as decreased all-cause mortality-including composite outcome of COVID-19 (0.89; 0.82–0.98; 0%). In subgroup analyses, all-cause mortality was significantly lower among COVID-19 patients being accompanied by severe ARDS but not mild ARDS, taking low-dose or pulse glucocorticoids, being critically severe but not only severe, being of critical severity and old but not young, being of critical severity and men but not women, non-early taking glucocorticoids, taking dexamethasone or methylprednisolone, and with the increased inflammatory state; but for SARS, lower mortality was observed among those who were taking medium-high dose glucocorticoids, being severe or critically severe, early taking glucocorticoids, and taking methylprednisolone or prednisolone.

Conclusions:

Glucocorticoids treatment reduced mortality in COVID-19 and SARS patients of critical severity; however, different curative effects existed between the two diseases among subpopulations, mainly regarding sex- and age-specific effects, optimal doses, and use timing of glucocorticoids.
Extracellular riboflavin induces anaerobic biofilm formation inShewanella oneidensis
Authors: Edel Miriam , Sturm Gunnar , Sturm-Richter Katrin , Wagner Michael , Ducassou Julia Novion , Couté Yohann , Horn Harald , Gescher Johannes
Published: February 2021

Some microorganisms can respire with extracellular electron acceptors using an extended electron transport chain to the cell surface. These organisms apply flavin molecules as cofactors to facilitate one-electron transfer catalysed by the terminal reductases and as endogenous electron shuttles. In the model organismShewanella oneidensis, riboflavin production and excretion triggers a specific biofilm formation response that is initiated at a specific threshold concentration, similar to canonical quorum sensing molecules. Riboflavin-mediated messaging is based on the overexpression of the gene encoding the putrescin decarboxylasespeCwhich leads to posttranscriptional overproduction of proteins involved in biofilm formation. Using a model of growth-dependent riboflavin production under batch and biofilm growth conditions, the number of cells necessary to produce the threshold concentration per time was deduced. Furthermore, our results indicate that specific retention of riboflavin in the biofilm matrix leads to localized concentrations which by far exceed the necessary threshold value.

Importance

Ferric iron is the fourth most abundant element of the earth crust. It occurs at neutral pH in the form insoluble iron minerals. The dissimilatory reduction of these minerals is an import part of global geological cycles and is catalyzed by microorganisms through extended respiratory chains to the cell surface.Shewanella oneidensisis one of the best understood model organisms for this kind of extracellular respiration. Flavins are important for the reduction of extracellular electron acceptors byS. oneidensis. since they have a function as (I) cofactors of the terminal reductases and (II) electron shuttles. In this study we reveal that flavin molecules are further employed as quorum sensing molecules. They are excreted by the organisms in a growth dependent manner and lead to anaerobic biofilm formation as a specific response at a certain threshold concentration. Although we know multiple examples of quorum sensing mechanisms, the use of riboflavin was so far not described and at least inS. oneidensisproceeds via a new regulatory routine that proceeds on the trancriptomic and posttranscriptomic level.
Messages From the Small Intestine Carried by Extracellular Vesicles in Prediabetes: a Proteomic Portrait
Authors: Ferreira Inês , de Oliveira Rita Machado , Carvalho Ana Sofia , Teshima Akiko , Beck Hans Christian , Matthiesen Rune , Costa-Silva Bruno , Macedo Maria Paula
Published: February 2021

Extracellular vesicles (EVs) mediate communication in physiological and pathological conditions. In the pathogenesis of type 2 diabetes, inter-organ communication plays an important role in its progress and metabolic surgery leads to its remission. Moreover, gut dysbiosis is emerging as a diabetogenic factor. However, it remains unclear how gut senses metabolic alterations and whether this is transmitted to other tissues via EVs. Using a diet induced-prediabetic mouse model, we observed that protein packaging in gut derived EVs (GDE), specifically small intestine, is increased in prediabetes. Proteins related to lipid metabolism and to oxidative stress management were more abundant in prediabetic GDE compared to healthy controls. On the other hand, proteins related to glycolytic activity, as well as those responsible for the degradation of polyubiquitinated composites, were depleted in prediabetic GDE. Together, our findings show that protein packaging in GDE is markedly modified during prediabetes pathogenesis. Thus, suggesting that prediabetic alterations in small intestine are translated into modified GDE proteome, which are dispersed into the circulation where they can interact with and influence the metabolic status of other tissues. This study highlights the importance of the small intestine as a tissue that propagates prediabetic metabolic dysfunction throughout the body and the importance of GDE as the messenger.
Comparing optimized exoskeleton assistance of the hip, knee, and ankle in single and multi-joint configurations
Authors: Franks Patrick W. , Bryan Gwendolyn M. , Martin Russell M. , Reyes Ricardo , Collins Steven H.
Published: February 2021

Exoskeletons that assist the hip, knee, and ankle joints have begun to improve human mobility, particularly by reducing the metabolic cost of walking. However, direct comparisons of optimal assistance of these joints, or their combinations, have not yet been possible. Assisting multiple joints may be more beneficial than the sum of individual effects, because muscles often span multiple joints, or less effective, because single-joint assistance can indirectly aid other joints. In this study, we used a hip-knee-ankle exoskeleton emulator paired with human-in-the-loop optimization to find single-joint, two-joint, and whole-leg assistance that maximally reduced the metabolic cost of walking for three participants. Hip-only and ankle-only assistance reduced the metabolic cost of walking by 26% and 30% relative to walking in the device unassisted, confirming that both joints are good targets for assistance. Knee-only assistance reduced the metabolic cost of walking by 13%, demonstrating that effective knee assistance is possible. Two-joint assistance reduced the metabolic cost of walking by between 34% and 42%, with the largest improvements coming from hip-ankle assistance. Assisting all three joints reduced the metabolic cost of walking by 50%, showing that at least half of the metabolic energy expended during walking can be saved through exoskeleton assistance. Changes in kinematics and muscle activity indicate that single-joint assistance indirectly assisted muscles at other joints, such that the improvement from whole-leg assistance was smaller than the sum of its single-joint parts. Exoskeletons can assist the entire limb for maximum effect, but a single well-chosen joint can be more efficient when considering additional factors such as weight and cost.
Parallel Characterization ofcis-Regulatory Elements for Multiple Genes Using CRISPRpath
Authors: Ren Xingjie , Wang Mengchi , Li Bingkun , Jamieson Kirsty , Zheng Lina , Jones Ian R. , Li Bin , Takagi Maya Asami , Lee Jerry , Maliskova Lenka , Tam Tsz Wai , Yu Miao , Hu Rong , Lee Lindsay , Abnousi Armen , Li Gang , Li Yun , Hu Ming , Ren Bing , Wang Wei , Shen Yin
Published: February 2021

Current pooled CRISPR screens forcis-regulatory elements (CREs) can only accommodate one gene based on its expression level. Here, we describe CRISPRpath, a scalable screening strategy for parallelly characterizing CREs of genes linked to the same biological pathway and converging phenotypes. We demonstrate the ability of CRISPRpath for simultaneously identifying functional enhancers of six genes in the 6-thioguanine-induced DNA mismatch repair pathway using both CRISPR interference (CRISPRi) and CRISPR nuclease (CRISPRn) approaches. 60% of the identified enhancers are known promoters with distinct epigenomic features compared to other active promoters, including increased chromatin accessibility and interactivity. Furthermore, by imposing different levels of selection pressure, CRISPRpath can distinguish enhancers exerting strong impact on gene expression from those exerting weak impact. Our results offer a nuanced view ofcis-regulation and demonstrate that CRISPRpath can be leveraged for understanding the complex gene regulatory program beyond transcriptional output at scale.
MVPA does not reveal neural representations of hierarchical linguistic structure in MEG
Authors: Arana Sophie , Schoffelen Jan-Mathijs , Mitchell Tom , Hagoort Peter
Published: February 2021

During comprehension, the meaning extracted from serial language input can be described by hierarchical phrase structure. Whether our brains explicitly encode hierarchical structure during processing is, however, debated. In this study we recorded Magnetoencephalography (MEG) during reading of structurally ambiguous sentences to probe neural activity for representations of underlying phrase structure. 10 human subjects were presented with simple sentences, each containing a prepositional phrase that was ambiguous with respect to its attachment site. Disambiguation was possible based on semantic information. We applied multivariate pattern analyses (MVPA) to the MEG data using linear classifiers as well as representational similarity analysis to probe various effects of phrase structure building on the neural signal. Using MVPA techniques we successfully decoded both syntactic (part-of-speech) as well as semantic information from the brain signal. Importantly, however, we did not find any patterns in the neural signal that differentiate between different hierarchical structures. Nor did we find neural traces of syntactic or semantic reactivation following disambiguating sentence material. These null findings suggest that subjects may not have processed the sentences with respect to their underlying phrase structure. We discuss methodological limits of our analysis as well as cognitive theories of “shallow processing”, i.e. in how far rich semantic information can prevent thorough syntactic analysis during processing.
Comparative Analysis of Genetically-Modified Crops: Conditional Equivalence Criteria
Authors: Jiang Changjian , Meng Chen , Schapaugh Adam W. , Jin Huizhe
Published: February 2021

The comparative assessment of genetically-modified (GM) crops relies on the principle of substantial equivalence, which states that such products should be compared to conventional counterparts that have an established history of safe use. In an effort to operationalize this principle, the GMO Panel of the European Food Safety Authority proposed an equivalence test that directly compares a GM test variety with a set of unrelated, conventionally-bred reference varieties with part of the difference as the known background of the test (the same as the given control). The criterion of the EFSA test, however, is defined solely by genotypic differences between the non-traited control and reference varieties (i.e. the background effect) while assuming the so-called GM trait effect as zero. As the outcome of an EFSA equivalence test is determined primarily by the similarity, or lack thereof, of the control and references, a conditional equivalence criterion is proposed in this investigation that focuses on “unintended” effects of a GM trait which is irrespective of the (random) genotypic value of a given control. The new criterion also includes a mean-scaled standard similar to the 80-125% rule for bioequivalence assessment practiced in the pharmaceutical industry as an alternative when the reference variation is zero or close to zero. In addition, optional criteria are proposed with a step-wise procedure to control the rate of false negatives (non-equivalence by chance) providing a comprehensive assessment under multiple comparisons. An application to maize grain composition data demonstrates that the conditional equivalence criterion provides effect-specific and more robust assessment of equivalence than the EFSA criterion did, especially for GM traits showing negligible or no unintended effects which are likely true for most traits in the current market.
Mosquito saliva sialokinin-dependent enhancement of arbovirus infection through endothelial barrier leakage
Authors: Lefteri Daniella A , Bryden Steven R , Pingen Marieke , Terry Sandra , Beswick Emily F , Georgiev Georgi , Van der Laan Marleen , Mastrullo Valeria , Campagnolo Paola , Waterhouse Robert , Varjak Margus , Merits Andres , Fragkoudis Rennos , Griffin Stephen , Shams Kave , Pondeville Emilie , McKimmie Clive S
Published: February 2021

Viruses transmitted byAedesmosquitoes constitute an increasingly important global health burden. Defining common determinants of host susceptibility to this large group of heterogenous pathogens are key for informing the rational design of new pan-viral medicines. Infection of the vertebrate host with these viruses is enhanced by the presence of mosquito saliva, a complex mixture of salivary gland-derived factors and microbiota. We show that enhancement of infection by saliva was dependent on vascular function and was independent of most anti-saliva immune responses, including to salivary microbiota. Instead, theAedesgene product sialokinin mediated enhancement of virus infection through a rapid reduction in endothelial barrier integrity. Sialokinin is unique within the insect world as having vertebrate-like tachykinin sequence and is absent from non-vector competentAnophelesmosquitoes, whose saliva was not pro-viral and did not induce similar vascular permeability. Therapeutic strategies targeting sialokinin have potential to limit disease severity following infection withAedesmosquito-borne viruses.
A single cell atlas of human teeth
Authors: Pagella Pierfrancesco , de Vargas Roditi Laura , Stadlinger Bernd , Moor Andreas E. , Mitsiadis Thimios A.
Published: February 2021

Teeth exert fundamental functions related to mastication and speech. Despite their great biomedical importance, an overall picture of their cellular and molecular composition is still missing. In this study, we have mapped the transcriptional landscape of the various cell populations that compose human teeth at single-cell resolution, and we analyzed in deeper detail their stem cell populations and their microenvironment. Our study identified great cellular heterogeneity in the dental pulp and the periodontium. Unexpectedly, we found that the molecular signatures of the stem cell populations were very similar, and that their distinctive behavior could be due to substantial differences between their microenvironments. Our findings suggest that the microenvironmental specificity is the potential source for the major functional differences of the stem cells located in the various tooth compartments and open new perspectives towards cell-based dental therapeutic approaches.
Relevance of network topology for the dynamics of biological neuronal networks
Authors: Mengiste Simachew Abebe , Aertsen Ad , Kumar Arvind
Published: February 2021

Complex random networks provide a powerful mathematical framework to study high-dimensional physical and biological systems. Several features of network structure (e.g. degree correlation, average path length, clustering coefficient) are correlated with descriptors of network dynamics and function. However, it is not clear which features of network structure relate to the dynamics of biological neuronal networks (BNNs), characterized by non-linear nodes with high in- and out degrees, but being weakly connected and communicating in an event-driven manner, i.e. only when neurons spike. To better understand the structure-dynamics relationship in BNNs, we analysed the structure and dynamics of > 9, 000 BNNs with different sizes and topologies. In addition, we also studied the effect of network degeneration on neuronal network structure and dynamics. Surprisingly, we found that the topological class (random, small-world, scale-free) was not an indicator of the BNNs activity state as quantified by the firing rate, network synchrony and spiking regularity. In fact, we show that different network topologies could result in similar activity dynamics. Furthermore, in most cases, the network activity changes did not depend on the rules according to which neurons or synapses were pruned from the networks. The analysis of dynamics and structure of the networks we studied revealed that the effective synaptic weight (ESW) was the most crucial feature in predicting the statistics of spiking activity in BNNs.ESWalso explained why different synapse and neuron pruning strategies resulted in almost identical effects on the network dynamics. Thus, our findings provide new insights into the structure-dynamics relationships in BNNs. Moreover, we argue that network topology and rules by which BNNs degenerate are irrelevant for BNN activity dynamics. Beyond neuroscience, our results suggest that in large networks with non-linear nodes, the effective interaction strength among the nodes, instead of the topological network class, may be a better predictor of the network dynamics and information flow.
Recoding enhances the metabolic capabilities of two novel methylotrophic Asgardarchaeota lineages
Authors: Sun Jiarui , Evans Paul N. , Gagen Emma J. , Woodcroft Ben J. , Hedlund Brian P. , Woyke Tanja , Hugenholtz Philip , Rinke Christian
Published: February 2021

Asgardarchaeota have been proposed as the closest living relatives to eukaryotes, and a total of 72 metagenome-assembled genomes (MAGs) representing six primary lineages in this archaeal phylum have thus far been described. These organisms are predicted to be fermentative organoheterotrophs contributing to carbon cycling in sediment ecosystems. Here, we double the genomic catalogue of Asgardarchaeota by obtaining 71 MAGs from a range of habitats around the globe, including deep subsurface, shallow lake, and geothermal spring sediments. Phylogenomic inferences followed by taxonomic rank normalisation confirmed previously established Asgardarchaeota classes and revealed four novel lineages, two of which were consistently recovered as monophyletic classes. We therefore propose the namesCandidatusHodarchaeia class nov. andCand.Jordarchaeia class nov., derived from the gods Hod and Jord in Norse mythology. Metabolic inference suggests that both novel classes represent methylotrophic acetogens, encoding the transfer of methyl groups, such as methylated amines, to coenzyme M with acetate as the end product in remnants of a methanogen-derived core metabolism. This inferred mode of energy conservation is predicted to be enhanced by genetic code expansions, i.e. recoding, allowing the incorporation of the rare 21st and 22nd amino acids selenocysteine (Sec) and pyrrolysine (Pyl). We found Sec recoding in Jordarchaeia and all other Asgardarchaeota classes, which likely benefit from increased catalytic activities of Sec-containing enzymes. Pyl recoding on the other hand is restricted to Hodarchaeia in the Asgardarchaeota, making it the first reported non-methanogenic lineage with an inferred complete Pyl machinery, likely providing this class with an efficient mechanism for methylamine utilisation. Furthermore, we identified enzymes for the biosynthesis of ester-type lipids, characteristic of Bacteria and Eukaryotes, in both novel classes, supporting the hypothesis that mixed ether-ester lipids are a shared feature among Asgardarchaeota.
Characterization of SdGA, a cold-adapted glucoamylase fromSaccharophagus degradans
Authors: Wayllace Natael M. , Hedín Nicolas , Busi María V. , Gomez-Casati Diego F.
Published: February 2021

We investigated the structural and functional properties of SdGA, a glucoamylase (GA) fromSaccharophagus degradans, a marine bacterium which degrades different complex polysaccharides at high rate. SdGA is composed mainly by a N-terminal GH15_N domain linked to a C-terminal catalytic domain (CD) found in the GH15 family of glycosylhydrolases with an overall structure similar to other bacterial GAs. The protein was expressed inEscherichia colicells, purified and its biochemical properties were investigated. Although SdGA has a maximum activity at 39°C and pH 6.0, it also shows high activity in a wide range, from low to mild temperatures, like cold-adapted enzymes. Furthermore, SdGA has a higher content of flexible residues and a larger CD due to various amino acid insertions compared to other thermostable GAs. We propose that this novel SdGA, is a cold-adapted enzyme that might be suitable for use in different industrial processes that require enzymes which act at low or medium temperatures.
Antiviral activity of influenza A virus defective interfering particles against SARS-CoV-2 replicationin vitrothrough stimulation of innate immunity
Authors: Rand U. , Kupke S.Y. , Shkarlet H. , Hein M.D. , Hirsch T. , Marichal-Gallardo P. , Cicin-Sain L. , Reichl U. , Bruder D.
Published: February 2021

SARS-CoV-2 causing COVID-19 emerged in late 2019 and resulted in a devastating pandemic. Although the first approved vaccines were already administered by the end of 2020, worldwide vaccine availability is still limited. Moreover, immune escape variants of the virus are emerging against which the current vaccines may confer only limited protection. Further, existing antivirals and treatment options against COVID-19 only show limited efficacy. Influenza A virus (IAV) defective interfering particles (DIPs) were previously proposed not only for antiviral treatment of the influenza disease but also for pan-specific treatment of interferon (IFN)-sensitive respiratory virus infections. To investigate the applicability of IAV DIPs as an antiviral for the treatment of COVID-19, we conductedin vitroco-infection experiments with cell culture-derived DIPs and the IFN-sensitive SARS-CoV-2 in human lung cells. We show that treatment with IAV DIPs leads to complete abrogation of SARS-CoV-2 replication. Moreover, this inhibitory effect was dependent on janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling. Further, our results suggest boosting of IFN-induced antiviral activity by IAV DIPs as a major contributor in suppressing SARS-CoV-2 replication. Thus, we propose IAV DIPs as an effective antiviral agent for treatment of COVID-19, and potentially also for suppressing the replication of new variants of SARS-CoV-2.
Fibroblasts – the neglected cell type in peripheral sensitization and chronic pain? - A systematic view on the current state of the literature
Authors: Shinotsuka Naomi , Denk Franziska
Published: February 2021

Chronic pain and its underlying biological mechanisms have been studied for many decades, with a myriad of molecules, receptors and cell types known to contribute to abnormal pain sensations. We now know that besides an obvious role for neuronal populations in the peripheral and central nervous system, immune cells like microglia, macrophages and T cells are also important drivers of persistent pain. While neuroinflammation has therefore been widely studied in pain research, there is one cell-type that appears to be rather neglected in this context: the humble fibroblast.

Fibroblasts may seem unassuming, but actually play a major part in regulating immune cell function and driving chronic inflammation. What is known about them in the context chronic pain?

Here we set out to analyze the literature on this topic – using systematic screening and data extraction methods to obtain a balanced view on what has been published. We found that there has been surprisingly little research in this area: 134 articles met our inclusion criteria, only a tiny minority of which directly investigated interactions between fibroblasts and peripheral neurons. We categorized the articles we included – stratifying them according to what was investigated, the estimated quality of results, and any common conclusions.

Fibroblasts are a ubiquitous cell type and a prominent source of many pro-algesic mediators in a wide variety of tissues. We think that they deserve a more central role in pain research and propose a new, testable model of how fibroblasts might drive peripheral neuron sensitization.
Dynamic Electrode-to-Image (DETI) Mapping Reveals the Human Brain’s Spatiotemporal Code of Visual Information
Authors: Hansen Bruce C. , Greene Michelle R. , Field David J.
Published: February 2021

A chief goal of systems neuroscience is to understand how the brain encodes information in our visual environments. Understanding that neural code is crucial to explaining how visual content is transformed via subsequent semantic representations to enable intelligent behavior. Although the visual code is not static, this reality is often obscured in voxel-wise encoding models of BOLD signals due to fMRI’s poor temporal resolution. We leveraged the high temporal resolution of EEG to develop an encoding technique based in state-space theory. This approach maps neural signals to each pixel within a given image and reveals location-specific transformations of the visual code, providing a spatiotemporal signature for the image at each electrode. This technique offers a spatiotemporal visualization of the evolution of the neural code of visual information thought impossible to obtain from EEG and promises to provide insight into how visual meaning is developed through dynamic feedforward and recurrent processes.
Circulating Low Density Neutrophils of Breast Cancer Patients are Associated with their Worse Prognosis due to the Impairment of T cell Responses
Authors: Saraiva Diana P. , Correia Bruna F. , Salvador Rute , de Sousa Nídia , Jacinto António , Braga Sofia , Cabral M. Guadalupe
Published: February 2021

Neutrophils are prominent immune components of solid tumors, which can protect against the onset of cancer (N1) or have pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN, a rare subset in non-pathological conditions, have been extensively studied in cancer, due to their frequency in this disease and their pro-tumor phenotype. However, this has been mainly demonstrated in animal models and proper validation in humans is an urgent need. Here, we further enlighten the clinical impact of LDN in a cohort of breast cancer (BC) patients. We observed that LDN were practically absent in healthy donors’ blood, while were significantly increased in the blood of BC patients, particularly with metastatic disease. Relevant for a clinical translation, within the population of non-metastatic patients, LDN were more prevalent in patients with poor response to neoadjuvant chemotherapy than in responders. The association of a higher incidence of circulating LDN and the worse prognosis of BC patients could be explained by the pro-tumor/immunosuppressive characteristics exhibited by these cells. Namely, there are more LDN expressing the immunosuppressive marker PD-L1, than HDN. Additionally, LDN also showed increased expression of activation markers; a robust formation of neutrophil extracellular traps; an augmented phagocytic activity; and a higher capacity to release reactive oxygen species, which may contribute for tumor development and metastization. Moreover, the percentage of LDN in BC patients’ blood was negatively correlated with activated cytotoxic T lymphocytes and positively correlated with the immunosuppressive CCR4+ regulatory T cells, corroborating their impairment on the anti-tumor immune responses, which was further demonstratedex vivo. Hence, this study reveals the potential of LDN as a clinical meaningful biomarker of BC response to treatment and opens new avenues for developing targeted immunotherapies.
Zooming into the genomic vicinity of the major locus for vicine and convicine in faba bean (Vicia fabaL.)
Authors: Tacke Rebecca , Ecke Wolfgang , Höfer Michael , Sass Olaf , Link Wolfgang
Published: February 2021

The versatility of faba bean (Vicia fabaL.) seed as valuable protein feed is hampered by its relatively high level of the compounds vicine and convicine (VC), which are antinutritive factors in poultry and further non-ruminant feed. The objective here was to develop the first-ever genetically low-VC winter faba bean. Hence, the low VC allele vc-, that should be the basis of a known, major locus for VC, need verification and molecular identification and be based on appropriately developed DNA-markers; the low VC feature awaited its transfer into the high-performing winter faba bean germplams. Based on bi-parental F2-families and isogenic lines, we thus developed highly useful SNP markers exploiting transcriptomic data. Furthermore, we fine-mapped and, based on synteny toMedicago truncatulaandCicer arietinum, we identified a candidate gene for the VC locus. A novel, genetically low VC winter faba bean population was bred. The path is now well-prepared for further marker-based breeding progress.
Impacts of an urban sanitation intervention on fecal indicators and the prevalence of human fecal contamination in Mozambique
Authors: Holcomb David A. , Knee Jackie , Capone Drew , Sumner Trent , Adriano Zaida , Nalá Rassul , Cumming Oliver , Brown Joe , Stewart Jill R.
Published: February 2021

Fecal source tracking (FST) may be useful to assess pathways of fecal contamination in domestic environments and to estimate the impacts of water, sanitation, and hygiene (WASH) interventions in low-income settings. We measured two non-specific and two human-associated fecal indicators in water, soil, and surfaces before and after a shared latrine intervention from low-income households in Maputo, Mozambique participating in the Maputo Sanitation (MapSan) trial. Up to a quarter of households were impacted by human fecal contamination, but trends were unaffected by improvements to shared sanitation facilities. The intervention reducedE. coligene concentrations in soil but did not impact culturableE. colior the prevalence of human FST markers in a difference-in-differences analysis. Using a novel Bayesian hierarchical modeling approach to account for human marker diagnostic sensitivity and specificity, we revealed a high amount of uncertainty associated with human FST measurements and intervention effect estimates. The field of microbial source tracking would benefit from adding measures of diagnostic accuracy to better interpret findings, particularly when FST analyses convey insufficient information for robust inference. With improved measures, FST could help identify dominant pathways of human and animal fecal contamination in communities and guide implementation of effective interventions to safeguard health.

SYNOPSIS

An urban sanitation intervention had minimal and highly uncertain effects on human fecal contamination after accounting for fecal indicator sensitivity and specificity.

TOC GRAPHIC/ABSTRACT ART
Competitive coordination of the dual roles of the Hedgehog co-receptor in homophilic adhesion and signal reception
Authors: Yang Shu , Zhang Ya , Yang Chuxuan , Wu Xuefeng , El Oud Sarah Maria , Chen Rongfang , Cai Xudong , Wu Xufeng S. , Lan Ganhui , Zheng Xiaoyan
Published: February 2021

Hedgehog (Hh) signaling patterns embryonic tissues and contributes to homeostasis in adults. InDrosophila, Hh transport and signaling are thought to occur along a specialized class of actin-rich filopodia, termed cytonemes. Here, we report that Interference hedgehog (Ihog) not only forms a Hh receptor complex with Patched to mediate intracellular signaling, but Ihog also engages intrans-homophilic binding leading to cytoneme stabilization in a manner independent of its role as the Hh receptor. Both functions of Ihog (trans-homophilic binding for cytoneme stabilization and Hh binding for ligand sensing) involve a region of the first fibronectin repeat of the extracellular domain. Thus, the Ihog-Ihog interaction and the Hh-Ihog interaction cannot occur simultaneously for a single Ihog molecule. By combining experimental data and mathematical modeling, we determined that Hh-Ihog heterophilic interaction dominates and Hh can disrupt and displace Ihog molecules involved intrans-homophilic binding. Consequently, we proposed that the weaker Ihog-Ihogtransinteraction promotes and stabilizes direct membrane contacts along cytonemes and that, as the cytoneme encounters secreted Hh ligands, the ligands trigger release of Ihog fromtransIhog-Ihog complex enabling transport or internalization of the Hh ligand-Ihog-Patched -receptor complex. Thus, the seemingly incompatible functions of Ihog in homophilic adhesion and ligand binding cooperate to assist Hh transport and reception along the cytonemes.

One-sentence summary

Apparently incompatible functions of Ihog in homophilic adhesion and ligand binding cooperate in Hh transport and reception.
No evidence for short-term evolutionary response to a warming environment in Drosophila
Authors: Santos Marta A. , Carromeu-Santos Ana , Quina Ana S. , Santos Mauro , Matos Margarida , Simões Pedro
Published: February 2021

Adaptive evolution is key in mediating responses to climate change. Such evolution will expectedly lead to changes in the populations’ thermal reaction norm and improve their ability to cope with stressful conditions. Conversely, constraints of different nature might limit the adaptive response. Here, we test these expectations by performing a real-time evolution experiment in historically differentiatedDrosophila subobscurapopulations. We address the phenotypic changes of flies evolving for nine generations in a daily fluctuating environment with average constant temperature, or a warming environment with increasing average and amplitude temperature across generations. Our results showed that (1) evolution under a global warming scenario has not led, so far, to a noticeable change in the thermal response; (2) historical background appears to be affecting the responses of populations under the warming environment, particularly at higher temperatures; (3) thermal reaction norms are trait-dependent: while lifelong exposure to low temperature decreases fecundity and productivity but not viability, high temperature causes negative transgenerational effects on productivity and viability, even though fecundity remains high. These findings raise concerns about the short-term efficiency of adaptive responses to the current changing climate.