bluuebunny/crossref_metadata_2025 huggingface dataset:
Spiritually and culturally sensitive evidence-based approaches to taking a spiritual history
Authors: Kao Larkin , Peteet John
Published: August 2021

Given the demonstrated relationship between religion and spirituality (R/S) and mental health, clinicians are faced with the decision of how to integrate R/S into clinical care. The first, most basic step to inform this decision is to ascertain a spiritual history. A skillful spiritual history can help the clinician to understand not only the patient’s R/S and whether they would like R/S involved in his clinical care, but also key mental health information, aiding in diagnosis and treatment planning. Studies have shown that patients want clinicians to ask about R/S, and that taking a spiritual history can correlate with improved patient treatment adherence, trust, and well-being. While many mental health professionals consider patient R/S to be important, few discuss R/S with patients in practice, and few training programs include guidance on the spiritual history. This chapter includes practical tools and considerations to consider when taking a spiritual history in various clinical and cultural scenarios. Basic tenets of taking a spiritual history are reviewed, along with the details of a few published tools for taking the spiritual history. The chapter concludes with a discussion of nuances in the spiritual history and a summary of areas for future study.
Religion and spirituality in prevention and promotion in mental health
Authors: Braam Arjan W.
Published: August 2021

The role religion and spirituality (R/S) can play in the promotion and prevention of mental health is not strictly defined, and the influence of culture is probably decisive. Aspects of R/S can be tentatively conceived of as epidemiological factors sometimes associated with better or poorer mental health (as is clear for at least one aspect—that is, religious struggle). Three main targets of prevention are suggested: (1) to consider how R/S may contribute to mental hygiene and educate accordingly, (2) to address religious struggle and positive elements of R/S in people with mental problems, and foster the therapeutic alliance and compliance, and (3) to prevent associated disabilities in those with mental disorders, and consider R/S as a field in need of care, with special attention to how R/S relates to existential concerns and the recovery process.
Geometry effects on dust attenuation curves with different grain sources at high redshift
Authors: Lin Yen-Hsing , Hirashita Hiroyuki , Camps Peter , Baes Maarten
Published: August 2021

Dust has been detected in high-redshift (z > 5) galaxies but its origin is still being debated. Dust production in high-redshift galaxies could be dominated by stellar production or by accretion (dust growth) in the interstellar medium. Previous studies have shown that these two dust sources predict different grain-size distributions, which lead to significantly different extinction curves. In this paper, by performing radiative transfer calculations, we investigate how the difference in the extinction curves affects the dust attenuation properties of galaxies. To examine the major effects of the dust–stars distribution geometry, we adopt two representative cases in spherical symmetry: the well-mixed geometry (stars and dust are homogeneously mixed) and the two-layer geometry (young stars are more concentrated in the centre). In both cases, we confirm that the attenuation curve can be drastically steepened by scattering and by different optical depths between young and old stellar populations, and can be flattened by the existence of unobscured stellar populations. We can reproduce similar attenuation curves even with very different extinction curves. Thus, we conclude that it is difficult to distinguish dust sources only with attenuation curves. However, if we include information on dust emission and plot the relation between infrared excess (IRX) and the ultraviolet spectral slope (β), then different dust sources predict different positions in the IRX–β diagram. A larger β is preferred under a similar IRX if dust growth is the dominant dust source.
Balmer-series spectral lines for hydrogen atoms in parallel magnetic and electric fields of white dwarfs
Authors: Zhao L B , Liu F L
Published: August 2021

We extended the two-dimensional B-spline approach recently developed to investigate the influence of a strong electric field on atomic structures and spectra for hydrogen atoms in magnetic fields of white dwarfs. Spectral lines for hydrogen in parallel magnetic and electric fields have been calculated. Wavelengths and oscillator strengths are presented for 14 Balmer α transitions as a function of magnetic and electric fields. The magnetic and electric field strengths involved span a scope, respectively, from around 23.5 to 2350 MG, and from 0 to 108 V/m. Our calculations show that the shift of Balmer-series spectral lines induced by a strong electric field reduces as the magnetic field strength increases. The obtained energy levels, wavelengths, and oscillator strengths are compared to available results in the literature, and excellent agreement was discovered. The spectral data reported in this paper can be applied to interpret the shifts of spectral lines of hydrogen in magnetic white dwarfs due to the presence of electric fields, and to predict additional spectral lines dipole-forbidden in a pure magnetic field.
Transposable element sequence fragments incorporated into coding and noncoding transcripts modulate the transcriptome of human pluripotent stem cells
Authors: Babarinde Isaac A , Ma Gang , Li Yuhao , Deng Boping , Luo Zhiwei , Liu Hao , Abdul Mazid Md , Ward Carl , Chen Minchun , Fu Xiuling , Shi Liyang , Duttlinger Martha , He Jiangping , Sun Li , Li Wenjuan , Zhuang Qiang , Tong Guoqing , Frampton Jon , Cazier Jean-Baptiste , Chen Jiekai , Jauch Ralf , Esteban Miguel A , Hutchins Andrew P
Published: August 2021

Transposable elements (TEs) occupy nearly 40% of mammalian genomes and, whilst most are fragmentary and no longer capable of transposition, they can nevertheless contribute to cell function. TEs within genes transcribed by RNA polymerase II can be copied as parts of primary transcripts; however, their full contribution to mature transcript sequences remains unresolved. Here, using long and short read (LR and SR) RNA sequencing data, we show that 26% of coding and 65% of noncoding transcripts in human pluripotent stem cells (hPSCs) contain TE-derived sequences. Different TE families are incorporated into RNAs in unique patterns, with consequences to transcript structure and function. The presence of TE sequences within a transcript is correlated with TE-type specific changes in its subcellular distribution, alterations in steady-state levels and half-life, and differential association with RNA Binding Proteins (RBPs). We identify hPSC-specific incorporation of endogenous retroviruses (ERVs) and LINE:L1 into protein-coding mRNAs, which generate TE sequence-derived peptides. Finally, single cell RNA-seq reveals that hPSCs express ERV-containing transcripts, whilst differentiating subpopulations lack ERVs and express SINE and LINE-containing transcripts. Overall, our comprehensive analysis demonstrates that the incorporation of TE sequences into the RNAs of hPSCs is more widespread and has a greater impact than previously appreciated.
Surgical versus conservative management of tongue lacerations in the acute care setting: A systematic review of the literature
Authors: Gonsalves Clarelle L , Zhu Jie Wei , Kim Grace Y , Leveille Cameron F , Kam April J
Published: August 2021

Objective

The objective of this study was to determine whether suturing or conservative management of tongue lacerations results in differences in wound healing and functional outcome. The secondary aim was to identify whether antibiotics are required in the treatment of tongue lacerations.

Methods

Studies published between December 1954 and August 2020 were extracted from MEDLINE via PubMed, Embase via OVID, CINAHL via EBSCO, Web of Science, and the Cochrane Library and evaluated for inclusion based on predetermined inclusion and exclusion criteria by two independent reviewers in accordance with PRISMA guidelines.

Results

The search yielded a total of 16,111 articles, 124 of which were evaluated by full-text review, resulting in 11 articles included in this systematic review representing 142 unique cases of tongue lacerations. At least 26 lacerations (18.3%) included penetration of the muscle layer of the tongue, and 24 (16.9%) were classified as full-thickness lacerations. Thirty-five of the 142 tongue lacerations (24.6%) were sutured. The remaining lacerations underwent some form of conservative management. The majority of studies reported excellent healing of tongue lacerations regardless of the management method, with minimal scarring and excellent return to normal functional status. No cases of infection were reported.

Conclusions

Current literature is inconsistent with regards to indications and guidelines for primary repair of tongue lacerations. The majority of tongue lacerations reported in the literature heal with excellent outcomes regardless of management method. Physician judgement along with patient and parental preference based on potential risks of the procedure should be used when deciding whether a tongue laceration requires primary repair. Tongue lacerations in otherwise healthy individuals are at very low risk of infection.
Are Positive Psychology Interventions Efficacious in Chronic Pain Treatment? A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Braunwalder Céline , Müller Rachel , Glisic Marija , Fekete Christine
Published: August 2021

Objective

Although positive psychology interventions (PPIs) are increasingly popular in chronic pain treatment their efficacy is still unclear. The objective is to summarize evidence on the effect of PPIs on pain, physical functioning, and emotional functioning in adults with chronic pain.

Methods

Four electronic databases and additional references were searched for randomized controlled trials (RCTs) published between 1990 and 2020. Findings from included studies were qualitatively and quantitatively synthesized, and study quality was assessed for risk of bias. A random effects meta-analysis model was applied for outcomes with more than four findings.

Results

Of 16 included RCTs, almost half delivered PPIs as self-help online interventions, and half conducted guided face-to-face interventions which lasted mostly eight weeks. Results from meta-analysis showed beneficial effects of PPIs compared to the control group on pain intensity and emotional functioning (i.e., less depressive symptoms, pain catastrophizing, negative affect; more positive affect) post-intervention. At 3-month follow-up, beneficial effects were maintained for depressive symptoms and positive and negative affect, but not for pain catastrophizing. However, the evidence on the long-term efficacy of PPIs and the efficacy of PPIs on physical functioning remains limited.

Conclusions

This review supports the notion that PPIs are beneficial to chronic pain treatment, although further, high quality research is needed to support this conclusion.
A sandwich structure composite wound dressing with firmly anchored silver nanoparticles for severe burn wound healing in a porcine model
Authors: Yang Jianmin , Huang Yufeng , Dai Jiajia , Shi Xianai , Zheng Yunquan
Published: August 2021

Wounds may remain open for a few weeks in severe burns, which provide an entry point for pathogens and microorganisms invading. Thus, wound dressings with long-term antimicrobial activity are crucial for severe burn wound healing. Here, a sandwich structure composite wound dressing anchored with silver nanoparticles (AgNPs) was developed for severe burn wound healing. AgNPs were in situ synthesized on the fibers of chitosan nonwoven fabric (CSNWF) as the interlayer of wound dressing for sustained release of silver ion. The firmly anchored AgNPs could prevent its entry into the body, thereby eliminating the toxicity of nanomaterials. The outer layer was a polyurethane membrane, which has a nanoporous structure that could maintain free transmission of water vapor. Chitosan/collagen sponge was selected as the inner layer because of its excellent biocompatibility and biodegradability. The presence of AgNPs in the CSNWF was fully characterized, and the high antibacterial activity of CSNWF/AgNPs was confirmed by against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The superior wound healing effect on deep dermal burns of presented composite wound dressing was demonstrated in a porcine model. Our finding suggested that the prepared AgNPs doped sandwich structure composite wound dressing has great potential application in severe wound care.
The effect of neural cell integrated into 3D co-axial bioprinted BMMSC structures during osteogenesis
Authors: Zhang Yi , Chen Haiyan , Long Xiaoyan , Xu Tao
Published: August 2021

A three-dimensional (3D) bioprinting is a new strategy for fabricating 3D cell-laden constructs that mimic the structural and functional characteristics of various tissues and provides a similar architecture and microenvironment of the native tissue. However, there are few reported studies on the neural function properties of bioengineered bone autografts. Thus, this study was aimed at investigating the effects of neural cell integration into 3D bioprinted bone constructs. The bioprinted hydrogel constructs could maintain long-term cell survival, support cell growth for human bone marrow-derived mesenchymal stem cells (BMMSCs), reduce cell surface biomarkers of stemness, and enhance orthopedic differentiation with higher expression of osteogenesis-related genes, including osteopontin (OPN) and bone morphogenetic protein-2. More importantly, the bioprinted constructs with neural cell integration indicated higher OPN gene and secretory alkaline phosphatase levels. These results suggested that the innervation in bioprinted bone constructs can accelerate the differentiation and maturation of bone development and provide patients with an option for accelerated bone function restoration.
Miscarriage, False Conceptions, and Other Lumps: Women’s Pregnancy Loss in Seventeenth- and Eighteenth-Century England
Authors: Donaghy Paige
Published: August 2021

Histories of early modern medicine and generation have tended to overlook the place that miscarriage, infertility, false conception and uterine diseases had in medical knowledge and women’s lives. By exploring English medical literature, casebooks, and letters, the study argues that a wide range of physical events, including miscarriage and false conception or mola, were experienced by women as a pregnancy, and then as the ‘loss of pregnancy’, or the loss of a potential infant. Early modern women often felt distress, grief and confusion at such losses, and medical practitioners formulated specific responses or treatments to these women’s experiences of losses. Considering miscarriage, false conception and uterine masses through the concept of ‘pregnancy loss’ challenges current narratives about generation. It shows that at this time a variety of gestational experiences, such as non-foetal gravidities and miscarriage formed part of ‘generation’, alongside the conception and birth of living infants.
Predicting ewe body condition score using adjusted liveweight for conceptus and fleece weight, height at withers, and previous body condition score record
Authors: Semakula Jimmy , Corner-Thomas Rene A , Morris Steve T , Blair Hugh T , Kenyon Paul R
Published: August 2021

The relationship between ewe body condition score (BCS) and liveweight (LW) has been exploited previously to predict the former from LW, LW-change, and previous BCS records. It was hypothesized that if fleece weight and conceptus-free liveweight and LW-change, and in addition, height at withers were used, the accuracy of current approaches to predicting BCS would be enhanced. Ewes born in 2017 (n = 429) were followed from 8 mo to approximately 42 mo of age in New Zealand. Individual ewe data were collected on LW and BCS at different stages of the annual production cycle (i.e., prebreeding, at pregnancy diagnosis, prelambing, and weaning). Additionally, individual lambing dates, ewe fleece weight, and height at withers data were collected. Linear regression models were fitted to predict current BCS at each ewe age and stage of the annual production cycle using two LW-based models, namely, unadjusted for conceptus weight and fleece weight (LW alone1) and adjusted (LW alone2) models. Furthermore, another two models based on a combination of LW, LW-change, previous BCS, and height at withers (combined models), namely, unadjusted (combined1) and adjusted for conceptus and fleece weight (combined2), were fitted. Combined models gave more accurate (with lower root mean square error: RMSE) BCS predictions than models based on LW records alone. However, applying adjusted models did not improve BCS prediction accuracy (or reduce RMSE) or improve model goodness of fit (R2) (P > 0.05). Furthermore, in all models, both LW-alone and combined models, a great proportion of variability in BCS, could not be accounted for (0.25 ≥ R2 ≥ 0.83) and there was substantial prediction error (0.33 BCS ≥ RMSE ≥ 0.49 BCS) across age groups and stages of the annual production cycle and over time (years). Therefore, using additional ewe data which allowed for the correction of LW for fleece and conceptus weight and using height at withers as an additional predictor did not improve model accuracy. In fact, the findings suggest that adjusting LW data for conceptus and fleece weight offer no additional value to the BCS prediction models based on LW. Therefore, additional research to identify alternative methodologies to account for individual animal variability is still needed.
Overexpression of geranyl diphosphate synthase (PmGPPS1) boosts monoterpene and diterpene production involved in the response to pine wood nematode invasion
Authors: Liu Bin , Liu Qinghua , Zhou Zhichun , Yin Hengfu , Xie Yini
Published: August 2021

Outbreaks of pine wood nematode (PWN; Bursaphelenchus xylophilus) represent a severe biotic epidemic for the Pinus massoniana in China. When invaded by the PWN, the resistant P. massoniana might secret abundant oleoresin terpenoid to form certain defensive fronts for survival. However, the regulatory mechanisms of this process remain unclear.

Here, the geranyl diphosphate synthase (PmGPPS1) gene was identified from resistant P. massoniana. Tissue-specific expression patterns of PmGPPS1 at transcript and protein level in resistant P. massoniana were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry. Functional characteristics analysis of PmGPPS1 was performed on transgenic Nicotiana benthamiana by overexpression, as genetic transformation of P. massoniana is, so far, not possible.

In summary, we identified and functionally characterized PmGPPS1 from the resistant P. massoniana following PWN inoculation. Tissue-specific expression patterns and localization of PmGPPS1 indicated that it may play a positive role involved in the metabolic and defensive processes of oleoresin terpenes production in response to PWN attack. Furthermore, overexpression of PmGPPS1 may enhance the production of monoterpene, among which limonene reduced the survival of PWN in vitro. In addition, PmGPPS1 upregulated the expression level of key genes involved in mevalonic acid (MVA) pathway, the methylerythritol phosphate (MEP) pathway and gibberellins (GAs) biosynthesis to boost the growth and development of tobacco through a feedback regulation mechanism.

Our results offered new insights into the pivotal role of the PmGPPS1 involved in terpene-based defense mechanisms responding to the PWN invasion in resistant P. massoniana and provided a new metabolic engineering scenario to improve monoterpene production in tobacco.
Agreed payment for non-performance under the Unidroit Principles and Arab region laws
Authors: Dawwas Amin
Published: August 2021

This article deals with parties’ pre-estimation of the amount of compensation for non-performance (liquidated damages, penalty clause). It discusses this agreed payment in terms of definition, validity, invocation, and possibility of adjustment upon the application of either party. The article presents the provisions of this legal institution in the Unidroit Principles, the Egyptian Civil Code, and the Jordanian Civil Code. It, first, draws a comparison between these laws in the Arab region and, second, considers them in relation to the Unidroit Principles to conclude with a solution that best serves the parties’ interests.
Trajectories of Worktime Control From Midlife to Retirement and Working Beyond Retirement Age
Authors: Virtanen Marianna , Myllyntausta Saana , Kauppi Maarit , Kivimäki Mika , Pentti Jaana , Ervasti Jenni , Prakash K C , Vahtera Jussi , Stenholm Sari
Published: August 2021

The extent to which long-term individual-oriented flexibility in working hours is associated with working beyond retirement age is not known. The aims of the present study were to identify trajectories of worktime control (WTC) and to examine whether the membership of WTC trajectories was associated with working beyond individual’s pensionable age. A total of 1,953 older employees participated in the study and had data up to 16 years before pensionable age. Group-based latent trajectory modeling was used to identify WTC trajectories and Cox proportional hazard regression models were used to examine the associations of WTC trajectories with duration of employment. Seven trajectories described WTC: “Stable very low” (7%), “Stable low” (21%), “Declined” (12%), “Stable mid-low” (28%), “Improved” (10%), “Stable high” (16%), and “Stable very high” (5%). When compared with the lowest WTC trajectory groups, trajectories of “Stable high/very high” (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.17–1.54) and “Improved” WTC (HR 1.49, 95% CI 1.25–1.78) were associated with longer duration of employment. Although the memberships of the “Stable high/very high” and “Improved” WTC trajectories correlated with gender, marital status, occupational position, and self-rated health, the association between WTC and duration of employment was not fully confounded or mediated by these factors. These findings support the hypothesis that having improved or constantly high control over working times from midlife to retirement age may prolong working lives at retirement age.
Phylogeny indicates polyphyly in Cnodocentron (Trichoptera: Xiphocentronidae): biogeography and revision of New World species (Caenocentron)
Authors: Vilarino Albane , Dias Everton Santos , Bispo Pitágoras Da Conceição
Published: August 2021

Cnodocentron has a disjunct Laurasian distribution, with species in South-East Asia and the New World. It is divided into two subgenera: Cnodocentron and Caenocentron. Here, we infer the evolutionary history of the genus through phylogenetic and biogeographic data combining COI and 46 morphological characters. Phylogenetic relationships and divergence-time estimation were simultaneously inferred through Bayesian inference. The dating analysis was performed through relaxed morphological and molecular clocks. The historical biogeography was investigated using the dispersal–extinction–cladogenesis model. Our results indicate the polyphyly of the genus Cnodocentron, with each subgenus being more related to other genera than to each other. Therefore, the subgenus Caenocentron is elevated to genus status here. The biogeographical analysis showed that the Oriental Cnodocentron diverged in the Indian subcontinent during the Middle Eocene, while the New World Caenocentron stat. nov. originated in the Chortis Block in the Late Eocene. The dispersal of Caenocentron to South America occurred only after the Late Miocene, around 10 Mya. Additionally, we provide a revision of Caenocentron, with an identification key and description of the male and female of two new species from Costa Rica: Caenocentron carlosdelarosai sp. nov. and Caenocentron rafamoralesi sp. nov..
Linking Climate Variables to Large-Scale Spatial Pattern and Risk of Citrus Huanglongbing: A Hierarchical Bayesian Modeling Approach
Authors: Alves Kaique S. , Rothmann Lisa A. , Del Ponte Emerson M.
Published: August 2021

Huanglongbing (HLB) is one of the most important diseases affecting citriculture in the world. Knowledge of climatic factors linked to HLB risk at large spatial scales is limited. We gathered HLB presence and absence data from official surveys conducted in the state of Minas Gerais, Brazil, over 13 years. The total count of orange and mandarin orchards, and mean orchard area, normalized to a spatial grid of 60 cells (55 × 55 km), were derived from the same database. Monthly climate normals (1984 to 2013) of rainfall, mean temperature, and wind speed split into rainy (September to April) and dry (May to August) seasons (annual summary was retained) were obtained for each grid cell. Two hierarchical Bayesian modeling approaches were evaluated, both based on the integrated nested Laplace approximation method. The first, the climate covariates model (CC model), used orchard, climate, and the spatial effect as covariates. The second, principal components (PC model), used the first three components from a principal component analysis of all variables and the spatial effect as covariates. Both models showed an inverse relationship between posterior prevalence and grid cell mean temperature during the dry season. Annual wind speed, as well as annual and rainy season rainfall, contributed to HLB risk in the CC and PC models, respectively. A partial influence of neighboring regions on HLB risk was observed. The results should assist policymakers in defining regions at HLB risk and guide monitoring strategies to mitigate further spread of HLB in the state of Minas Gerais.
Thermococcus aciditolerans sp. nov., a piezotolerant, hyperthermophilic archaeon isolated from a deep-sea hydrothermal vent chimney in the Southwest Indian Ridge
Authors: Li Xue-Gong , Tang Hong-Zhi , Zhang Wei-Jia , Qi Xiao-Qing , Qu Zhi-Guo , Xu Jun , Wu Long-Fei
Published: August 2021

A hyperthermophilic, strictly anaerobic archaeon, designated strain SY113T, was isolated from a deep-sea hydrothermal vent chimney on the Southwest Indian Ridge at a water depth of 2770 m. Enrichment and isolation of strain SY113Twere performed at 85 °C at 0.1 MPa. Cells of strain SY113Twere irregular motile cocci with peritrichous flagella and generally 0.8–2.4 µm in diameter. Growth was observed at temperatures between 50 and 90 °C (optimum at 85 °C) and under hydrostatic pressures of 0.1–60 MPa (optimum, 27 MPa). Cells of SY113Tgrew at pH 4.0–9.0 (optimum, pH 5.5) and a NaCl concentration of 0.5–5.5 % (w/v; optimum concentration, 3.0 % NaCl). Strain SY113Twas an anaerobic chemoorganoheterotroph and grew on complex proteinaceous substrates such as yeast extract and tryptone, as well as on maltose and starch. Elemental sulphur stimulated growth, but not obligatory for its growth. The G+C content of the genomic DNA was 55.0 mol%. Phylogenetic analysis of the 16S rRNA sequence of strain SY113Tshowed that the novel isolate belonged to the genusThermococcus. On the basis of physiological characteristics, average nucleotide identity values andin silicoDNA–DNA hybridization results, we propose a novel species, namedThermococcus aciditoleranssp. nov. The type strain is SY113T(=MCCC 1K04190T=JCM 39083T).
Emendation of General Consideration 5 and Rules 18a, 24a and 30 of the International Code of Nomenclature of Prokaryotes to resolve the status of the Cyanobacteria in the prokaryotic nomenclature
Authors: Oren Aharon , Arahal David R. , Rosselló-Móra Ramon , Sutcliffe Iain C. , Moore Edward R. B.
Published: August 2021

Following the International Committee on Systematics of Prokaryotes electronic discussion and vote on proposals to resolve the status of the

Cyanobacteria

in the prokaryotic nomenclature, we announce here the results of the ballot. We also present the emended versions of General Consideration 5 and Rules 18a, 24a and 30, based on the outcome of the ballot, to be included in the new revision of the International Code of Nomenclature of Prokaryotes.
Cancer-associated fibroblasts exert a pro-angiogenic activity in Merkel cell carcinoma
Authors: Albertini Silvia , Martuscelli Licia , Borgogna Cinzia , Virdi Sanamjeet , Indenbirken Daniela , Cigno Irene Lo , Griffante Gloria , Calati Federica , Boldorini Renzo , Fischer Nicole , Gariglio Marisa
Published: August 2021

The tumor microenvironment (TME) is a complex niche enveloping a tumor formed by extracellular matrix, blood vessels, immune cells, and fibroblasts constantly interacting with cancer cells. Although TME is increasingly recognized as a major player in cancer initiation and progression in many tumor types, its involvement in Merkel cell carcinoma (MCC) pathogenesis is currently unknown. Here, we provide the first molecular and functional characterization of cancer- associated fibroblasts (CAFs), the major TME component, in MCC patient-derived xenografts. We show that subcutaneous co-injection of patient-derived CAFs and human MCC MKL-1 cells into SCID mice significantly promotes tumor growth and metastasis. These fast-growing xenografts are characterized by areas densely populated with human CAFs, mainly localized around blood vessels. We also provide evidence that the growth-promoting activity of MCC-derived CAFs is mediated by the APA/Ang II-III/AT1R axis, with the expression of aminopeptidase A (APA) in CAFs being the upstream triggering event. Altogether, our findings point to APA as a potential marker for MCC prognostic stratification and a novel candidate therapeutic target.
Multi-Task Brain Network Reconfiguration is Inversely Associated with Human Intelligence
Authors: Thiele Jonas A. , Faskowitz Joshua , Sporns Olaf , Hilger Kirsten
Published: August 2021

Intelligence describes the general cognitive ability level of a person. It is one of the most fundamental concepts in psychological science and is crucial for effective adaption of behavior to varying environmental demands. Changing external task demands have been shown to induce reconfiguration of functional brain networks. However, whether neural reconfiguration between different tasks is associated with intelligence has not yet been investigated. We used fMRI data from 812 subjects to show that higher scores of general intelligence are related to less brain network reconfiguration between resting state and seven different task states as well as to network reconfiguration between tasks. This association holds for all functional brain networks except the motor system, and replicates in two independent samples (N = 138, N = 184). Our findings suggest that the intrinsic network architecture of individuals with higher intelligence scores is closer to the network architecture as required by various cognitive demands. Multi-task brain network reconfiguration may, therefore, represent a neural reflection of the behavioral positive manifold – the essence of the concept of general intelligence. Finally, our results support neural efficiency theories of cognitive ability and reveal insights into human intelligence as an emergent property from a distributed multi-task brain network.
Membrane channel hypothesis of lysosomal permeabilization by beta-amyloid
Authors: Zaretsky Dmitry V. , Zaretskaia Maria V. , Molkov Yaroslav I.
Published: August 2021

Alzheimer’s disease (AD) is the most common cause of dementia affecting millions of people. Neuronal death in AD is initiated by oligomeric amyloid-β (Aβ) peptides. Recently, we proposed the amyloid degradation toxicity hypothesis, which explains multiple major observations associated with AD – such as autophagy failure and a decreased metabolism. According to the hypothesis, the key event in the cellular toxicity of amyloid is the formation of non-selective membrane channels in lysosomal membranes by amyloid fragments that are produced by the digestion of Aβ previously absorbed by endocytosis. Electrophysiological data suggest that amyloid-formed channels have different sizes, which can be explained by the fact that barrel-shaped amyloid aggregates which create channels can consist of different number of monomers.

To estimate the ability of channels to leak molecules of various molecular weights, we modeled the channels as saline-filled cylinders in non-conductive membranes that pass spheres with a density of average globular proteins. As a basis, we used the conductance distribution taken from the previously published experimental dataset, in which single channels with a conductance reaching one nanosiemens were registered. Our calculations show that channels with a giant conductance can allow for passing macromolecules such as lysosomal cathepsins implicated in the activation of apoptosis. The formation of giant channels is disproportionally promoted in an acidic environment. Also, amyloid fragments leaking from permeabilized lysosomes can reach the internal leaflet of the plasma membrane and permeabilize it.

We conclude that while dissipation of the proton gradient by any – even the smallest amyloid channel – readily explains lysosomal failure, the relatively rare events of lysosomal permeabilization to large macromolecules can be an alternative mechanism of cellular death induced by exposure to Aβ.
Activity Space Maps: a novel human mobility data set for quantifying time spent at risk
Authors: Citron Daniel T. , Iyer Shankar , Reiner Robert C. , Smith David L.
Published: August 2021

Activity Space Maps are a novel global-scale movement and mobility data set which describes how people distribute their time through geographic space. The maps are intended for use by researchers for the purposes of epidemiological modeling. Activity Space Maps are designed to complement existing digitally-collected mobility data sets by quantifying the amount of time that people spend in different locations. This information is important for estimating the duration of contact with the environment and the potential risk of exposure to disease. More concretely, the type of information contained in Activity Space Maps will make it easier to model the spatial transmission patterns of vector-borne diseases like malaria and Dengue fever. We will discuss the motivation for designing Activity Space Maps, how the maps are generated from mobile phone user app location history data, and discuss an example use case demonstrating how such data may be used together with spatial epidemiological data to advance our understanding of spatial disease patterns and the relationship between travel behaviors and infection risk.
The spike protein of SARS-CoV-2 induces endothelial inflammation through integrin α5β1 and NF-κB
Authors: Robles Juan Pablo , Zamora Magdalena , de la Escalera Gonzalo Martinez , Clapp Carmen
Published: August 2021

Vascular endothelial cells (EC) form a critical interface between blood and tissues that maintains whole-body homeostasis. In COVID-19, disruption of the EC barrier results in edema, vascular inflammation, and coagulation, the hallmarks of the severe disease. However, the mechanisms by which EC are dysregulated in COVID-19 are unclear. Here, we show that the spike protein of SARS-CoV-2 alone activates the EC inflammatory phenotype in a manner dependent on integrin α5β1 signaling. Incubation of human umbilical vein EC with whole spike, its receptor-binding domain, or the integrin-binding tripeptide RGD induced the nuclear translocation of NF-κB and enhanced the expression of leukocyte adhesion molecules VCAM1 and ICAM1, the adhesion of peripheral blood leukocytes, and the permeability of the monolayer. Inhibitors of integrin α5β1 activation prevented these effects. We suggest that the spike protein, through its RGD motif in the receptor-binding domain, binds to integrin α5β1 in EC to activate Rho GTPases, eNOS pathways, and the NF-κB gene expression program responsible for vascular leakage and leukocyte infiltration, respectively. These findings uncover a new direct action of SARS-CoV-2 on EC dysfunction and introduce integrin α5β1 as a promising target for treating vascular inflammation in COVID-19.
Langerhans cells and cDC1s play redundant roles in mRNA-LNP induced protective anti-influenza and anti-SARS-CoV-2 responses
Authors: Ndeupen Sonia , Bouteau Aurélie , Herbst Christopher , Qin Zhen , Hutchins Zachary , Kurup Drishya , Diba Leila Zabihi , Igyártó Botond Z.
Published: August 2021

Nucleoside modified mRNA combined with Acuitas Therapeutics’ lipid nanoparticles (LNP) have been shown to support robust humoral immune responses in many preclinical animal vaccine studies and later in humans with the SARS-CoV-2 vaccination. We recently showed that this platform is highly inflammatory due to the LNPs’ ionizable lipid component. The inflammatory property is key to support the development of potent humoral immune responses. However, the mechanism by which this platform drives T follicular helper cells (Tfh) and humoral immune responses remains unknown. Here we show that lack of Langerhans cells or cDC1s neither significantly affected the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cells and humoral immune responses, nor susceptibility towards the lethal challenge of influenza and SARS-CoV-2. However, the combined deletion of these two DC subsets led to a significant decrease in the induction of PR8 HA and SARS-CoV-2 RBD-specific Tfh cell and humoral immune responses. Despite these observed defects, the still high antibody titers were sufficient to confer protection towards lethal viral challenges. We further found that IL-6, but not neutrophils, was required to generate Tfh cells and antibody responses.

In summary, here we bring evidence that the mRNA-LNP platform can support protective adaptive immune responses in the absence of specific DC subsets through an IL-6 dependent and neutrophil independent mechanism.
A mechanosensing mechanism mediated by IRSp53 controls plasma membrane shape homeostasis at the nanoscale
Authors: Quiroga Xarxa , Walani Nikhil , Chavero Albert , Mittens Alexandra , Disanza Andrea , Tebar Francesc , Trepat Xavier , Parton Robert G. , Scita Giorgio , Geli Maria Isabel , Arroyo Marino , Le Roux Anabel-Lise , Roca-Cusachs Pere
Published: August 2021

As cells migrate and experience forces from their surroundings, they constantly undergo mechanical deformations which reshape their plasma membrane (PM). To maintain homeostasis, cells need to detect and restore such changes, not only in terms of overall PM area and tension as previously described, but also in terms of local, nano-scale topography. Here we describe a novel phenomenon, by which cells sense and restore mechanically induced PM nano-scale deformations. We show that cell stretch and subsequent compression reshape the PM in a way that generates local membrane evaginations in the 100 nm scale. These evaginations are recognized by the I-BAR protein IRSp53, which triggers a burst of actin polymerization mediated by Rac1 and Arp2/3. The actin polymerization burst subsequently re-flattens the evagination, completing the mechanochemical feedback loop. Our results demonstrate a new mechanosensing mechanism for PM shape homeostasis, with potential applicability in different physiological scenarios.

Teaser

Cell stretch cycles generate PM evaginations of ≈100 nm which are sensed by IRSp53, triggering a local event of actin polymerization that flattens and recovers PM shape.
Dynamic inventory of moths of Savitribai Phule Pune University (Pune, India) through crowdsourcing via iNaturalist
Authors: Pujari Bhalchandra
Published: August 2021

We present here the checklist of moths (Lepidoptera: Heterocera) for the campus of Savitribai Phule Pune University, situated in the metropolis of Pune in the state Maharashra in India. We report identification of 189 unique genera along with 154 unique species. Despite the relative small size of the observation area and the location being at the heart of a busy metropolis, the moths were found to be of diverse variety, with 26 different families and 76 tribes.

The identifications of the species was crowd-sourced via iNaturalist.org. An automated program was developed to fetch the identification and generate the list. The program is also being made available open source. As a result the checklist remains relevant all the time with newer identification, correcting existing identification (if required) and taxonomic updates of the future.
Allosteric perspective on the mutability and druggability of the SARS-CoV-2 Spike protein
Authors: Tan Zhen Wah , Tee Wei-Ven , Samsudin Firdaus , Guarnera Enrico , Bond Peter J. , Berezovsky Igor N.
Published: August 2021

Recent developments in the SARS-CoV-2 pandemic point to its inevitable transformation into an endemic disease, urging both diagnostics of emerging variants of concern (VOCs) and design of the variant-specific drugs in addition to vaccine adjustments. Exploring the structure and dynamics of the SARS-CoV-2 Spike protein, we argue that the high mutability characteristic of RNA viruses coupled with the remarkable flexibility and dynamics of viral proteins result in a substantial involvement of allosteric mechanisms. While allosteric effects of mutations should be considered in predictions and diagnostics of new VOCs, allosteric drugs advantageously avoid escaping mutations via non-competitive inhibition originating from many alternative distal locations. The exhaustive allosteric signalling and probing maps provide a comprehensive picture of allostery in the Spike protein, making it possible to locate sites of potential mutations that could work as new VOCs “drivers”, and to determine binding patches that may be targeted by newly developed allosteric drugs.
Colon epithelial cell-specific Bmal1 deletion impairs bone formation in mice
Authors: Ko Frank C. , Jochum Sarah B. , Wilson Brittany M. , Adra Amal , Patel Nikhil , Wilber Sherry , Shaikh Maliha , Forsyth Christopher , Keshavarzian Ali , Swanson Garth R. , Rick Sumner D.
Published: August 2021

The circadian clock system regulates multiple metabolic processes, including bone metabolism. Previous studies have demonstrated that both central and peripheral circadian signaling regulate skeletal growth and homeostasis. Disruption in central circadian rhythms has been associated with a decline in bone mineral density and the global and osteoblast-specific disruption of clock genes in bone tissue leads to lower bone mass. Gut physiology is highly sensitive to circadian disruption. Since the gut is also known to affect bone remodeling, we sought to test the hypothesis that circadian signaling disruption in colon epithelial cells affects bone. We therefore assessed structural, functional, and cellular properties of bone in 8 week old Ts4-Cre and Ts4-Cre;Bmal1fl/fl (cBmalKO) mice, where the clock gene Bmal1 is deleted in colon epithelial cells. Axial and appendicular trabecular bone volume was significantly lower in cBmalKO compared to Ts4-Cre 8-week old mice in a sex-dependent fashion, with male but not female mice showing the phenotype. Similarly, the whole bone mechanical properties were deteriorated in cBmalKO male mice. The tissue level mechanisms involved suppressed bone formation with normal resorption, as evidenced by serum markers and dynamic histomorphometry. Our studies demonstrate that colon epithelial cell-specific deletion of Bmal1 leads to trabecular and cortical bone loss in male mice.
Microbial community of recently discovered Auka vent field sheds light on vent biogeography and evolutionary history of thermophily
Authors: Speth Daan R. , Yu Feiqiao B. , Connon Stephanie A. , Lim Sujung , Magyar John S. , Peña Manet E. , Quake Stephen R. , Orphan Victoria J.
Published: August 2021

Hydrothermal vents have been key to our understanding of the limits of life, and the metabolic and phylogenetic diversity of thermophilic organisms. Here we used environmental metagenomics combined with analysis of physico-chemical data and 16S rRNA amplicons to characterize the diversity, temperature optima, and biogeographic distribution of sediment-hosted microorganisms at the recently discovered Auka vents in the Gulf of California, the deepest known hydrothermal vent field in the Pacific Ocean. We recovered 325 metagenome assembled genomes (MAGs) representing 54 phyla, over 1/3 of the currently known phylum diversity, showing the microbial community in Auka hydrothermal sediments is highly diverse. Large scale 16S rRNA amplicon screening of 227 sediment samples across the vent field indicates that the MAGs are largely representative of the microbial community. Metabolic reconstruction of a vent-specific, deeply branching clade within the Desulfobacterota (Tharpobacteria) suggests these organisms metabolize sulfur using novel octaheme cytochrome-c proteins related to hydroxylamine oxidoreductase. Community-wide comparison of the average nucleotide identity of the Auka MAGs with MAGs from the Guaymas Basin vent field, found 400 km to the Northwest, revealed a remarkable 20% species-level overlap between vent sites, suggestive of long-distance species transfer and sediment colonization. An adapted version of a recently developed model for predicting optimal growth temperature to the Auka and Guaymas MAGs indicates several of these uncultured microorganisms could grow at temperatures exceeding the currently known upper limit of life. Extending this analysis to reference data shows that thermophily is a trait that has evolved frequently among Bacteria and Archaea. Combined, our results show that Auka vent field offers new perspectives on our understanding of hydrothermal vent microbiology.
Myth-busting the provider-user relationship for digital sequence information
Authors: Scholz Amber Hartman , Lange Matthias , Habekost Pia , Oldham Paul , Cancio Ibon , Cochrane Guy , Freitag Jens
Published: August 2021

The United Nations Convention on Biological Diversity (CBD) formally recognized the sovereign rights of nations over their biological diversity. Implicit within the treaty is the idea that mega-biodiverse countries will provide genetic resources and grant access to them and scientists in high-income countries will use these resources and share back benefits. However, little research has been conducted on how this framework is reflected in real-life scientific practice. Currently, parties to the CBD) are debating whether or not digital sequence information (DSI) should be regulated under a new benefit-sharing framework. At this critical time point in the upcoming international negotiations, we test the fundamental hypothesis of provision and use by looking at the global patterns of access and use in scientific publications. Our data reject the provider-user relationship and suggest far more complex information flow for digital sequence information. Therefore, any new policy decisions on digital sequence information should be aware of the high level of use of DSI across low- and middle-income countries and seek to preserve open access to this crucial common good.