bluuebunny/crossref_metadata_2025 huggingface dataset:
Pitch and Duration Mismatch Negativity are Associated With Distinct Auditory Cortex and Inferior Frontal Cortex Volumes in the First-Episode Schizophrenia Spectrum
Authors: Curtis Mark T , Coffman Brian A , Salisbury Dean F
Published: February 2021

Background

Pitch and duration mismatch negativity (pMMN/dMMN) are related to left Heschl’s gyrus gray matter volumes in first-episode schizophrenia (FESz). Previous methods were unable to delineate functional subregions within and outside Heschl’s gyrus. The Human Connectome Project multimodal parcellation (HCP-MMP) atlas overcomes this limitation by parcellating these functional subregions. Further, MMN has generators in inferior frontal cortex, and therefore, may be associated with inferior frontal cortex pathology. With the novel use of the HCP-MMP to precisely parcellate auditory and inferior frontal cortex, we investigated relationships between gray matter and pMMN and dMMN in FESz.

Methods

pMMN and dMMN were measured at Fz from 27 FESz and 27 matched healthy controls. T1-weighted MRI scans were acquired. The HCP-MMP atlas was applied to individuals, and gray matter volumes were calculated for bilateral auditory and inferior frontal cortex parcels and correlated with MMN. FDR correction was used for multiple comparisons.

Results

In FESz only, pMMN was negatively correlated with left medial belt in auditory cortex and area 47L in inferior frontal cortex. Duration MMN negatively correlated with the following auditory parcels: left medial belt, lateral belt, parabelt, TA2, and right A5. Further, dMMN was associated with left area 47L, right area 44, and right area 47L in inferior frontal cortex.

Conclusions

The novel approach revealed overlapping and distinct gray matter associations for pMMN and dMMN in auditory and inferior frontal cortex in FESz. Thus, pMMN and dMMN may serve as biomarkers of underlying pathological deficits in both similar and slightly different cortical areas.
Banning Because of Science or In Spite of it? Scientific Authority, Religious Conservatism, and Support for Outlawing Pornography, 1984–2018
Authors: Perry Samuel L
Published: February 2021

For decades anti-pornography sentiment and campaigns were driven largely by religious conservatives citing pornography’s “contaminating” moral effects. More recently, however, anti-porn campaigns have sought to support their arguments by appealing to social and cognitive science. This raises the question of whether anti-pornography sentiment is undergoing an “internal secularization,” reflected in a growing connection to scientific authority and weakening connection to religious authority, or conversely, whether the use of “science” reflects a more symbolic and tactical framing used by religious conservatives who already oppose pornography. Using the General Social Surveys (1984–2018), I examine how trust in scientific authority and traditional measures of religious conservatism are associated with anti-pornography sentiment and how these associations have changed since the mid-1980s. The positive association between religious conservatism and support for anti-pornography legislation has either remained the same or, in the case of biblical literalism, grown stronger. In contrast, Americans with greater confidence in science or scientists are less likely to support outlawing pornography, and this pattern has not reversed. Indeed, in recent decades, Americans across all levels of confidence in science have declined in their support for banning porn and now differ only minimally. Together these patterns suggest anti-porn sentiment is actually desecularizing, growing more connected to religious conservatism than views about scientific authority. Findings suggest current anti-pornography sentiment does not stem from scientific authority gaining ground among Americans who oppose pornography. Rather, citing scientific research likely reflects efforts to leverage its cultural authority among those already morally inclined to restrict porn’s availability.
Mendelian randomization highlights insomnia as a risk factor for pain diagnoses
Authors: Broberg Martin , Karjalainen Juha ,   FinnGen, Ollila Hanna M
Published: February 2021

Study Objective

Insomnia has been linked to acute and chronic pain conditions; however, it is unclear whether such relationships are causal. Recently, a large number of genetic variants have been discovered for both insomnia and pain through genome-wide association studies (GWASs) providing a unique opportunity to examine the evidence for causal relationships through the use of the Mendelian randomization paradigm.

Methods

To elucidate the causality between insomnia and pain, we performed bidirectional Mendelian randomization analysis in FinnGen, where clinically diagnosed ICD-10 categories of pain had been evaluated. In addition, we used measures of self-reported insomnia symptoms. We used endpoints for pain in the FinnGen Release 5 (R5) (N = 218,379), and a non-overlapping sample for insomnia (UK Biobank (UKBB) and 23andMe, N = 1,331,010 or UKBB alone N = 453,379). We assessed the robustness of results through conventional Mendelian randomization sensitivity analyses.

Results

Genetic liability to insomnia symptoms increased the odds of reporting pain (odds ratio (OR) [95% confidence interval (CI)] = 1.47 [1.38–1.58], p = 4.12 × 10−28). Manifested pain had a small effect on increased risk for insomnia (OR [95% CI] = 1.04 [1.01–1.07], p < 0.05). Results were consistent in sensitivity analyses.

Conclusions

Our findings support a bidirectional causal relationship between insomnia and pain. These data support a further clinical investigation into the utility of insomnia treatment as a strategy for pain management and vice versa.
Sleep quality deterioration in middle-aged and older adults living in a rural Ecuadorian village severely struck by the SARS-CoV-2 pandemic. A population-based longitudinal prospective study
Authors: Del Brutto Oscar H , Mera Robertino M , Costa Aldo F , Recalde Bettsy Y , Castillo Pablo R
Published: February 2021

Study Objectives

This study assessed changes in sleep quality before and after the peak of the SARS-CoV-2 pandemic in community dwellers enrolled in the Atahualpa Project.

Methods

Atahualpa residents aged ≥40 years were eligible if they had a Pittsburgh Sleep Quality Index (PSQI) 9 months before the pandemic and a lateral flow-based test for identification of SARS-CoV-2 antibodies during the peak of the pandemic. Six months later, individuals completed a follow-up PSQI. The independent relationship between SARS-CoV-2 infection and deterioration in sleep quality was assessed by fitting logistic mixed models for longitudinal data.

Results

Of 639 participants (mean age at baseline: 59 ± 12.8 years), 325 (51%) had SARS-CoV-2 antibodies. A total of 185 (29%) individuals at baseline and 311 (49%) at follow-up were poor sleepers (p < 0.001). Mixed logistic regression models demonstrated a significant increase in poor sleepers at follow-up (odds ratio [OR]: 2.85; 95% CI: 2.16 to 3.75), which was more marked among SARS-CoV-2 seropositive subjects (OR: 3.8; 95% CI: 2.48 to 5.81). The adjusted proportion of poor sleepers increased from 29% to 56.2% (95% CI: 50.9% to 61.6%) among SARS-CoV-2 seropositive individuals, but only to 40.7% (95% CI: 35.3% to 46.1%) in their seronegative counterparts (p < 0.001). Likewise, progression from a good to a poor sleeper status was higher among seropositive individuals than in their seronegative counterparts (38.1% vs 22.3%; p < 0.001), after adjusting for relevant covariates.

Conclusions

This study shows a deleterious effect of SARS-CoV-2 in sleep quality. An effect of SARS-CoV-2 in disrupting sleep-related pathways cannot be ruled out.

Trial registration

The Atahualpa Project has been registered at ClinicalTrials.gov; the identifier number is NCT01627600, and the date was: 10/02/2012 (https://clinicaltrials.gov/ct2/show/NCT01627600?cond=Atahualpa&draw=2&rank=1). The Sleep Disorders substudy has been registered at ClinicalTrials.gov; the identifier number is NCT01877616, and the date was: 06/13/2013 (https://clinicaltrials.gov/ct2/show/NCT01877616?cond=Atahualpa&draw=2&rank=4).
Fluctuating Palmar Erythema in a Toddler during COVID-19 Pandemic: Do You Know the Offender?
Authors: Panda Prateek Kumar , Sharawat Indar Kumar
Published: February 2021

Palmar erythema in children can be due to various reasons, such as chronic liver disease, rheumatological disorders, medications, irritant contact dermatitis and atopic dermatitis. Recently, there are few reports about contact dermatitis caused by frequent, daily use of hand sanitizers during this COVID-19 pandemic. A 3-year-old toddler brought with the concern of waxing-waning bilateral palmar erythema for the past 2 weeks. The parents revealed that the child liked the bright color of a recently bought hand sanitizer bottle so much he used to wash his hands every 20–30 min throughout the day. The atypical presentation of contact dermatitis might be because the child was using the sanitizer more frequently during the daytime. The dermatitis resolved with stopping excessive use of the hand sanitizer by the toddler. Clinicians should be aware of contact dermatitis during these pandemic times. Instead of investigating them extensively, careful history taking and merely advising them to judicially utilize the sanitizer can lead to complete reversal of symptoms.
Tuberous Sclerosis Complex: Early Screening and Infant Outcome in NICU
Authors: Su Yajie , Wei Qiufen , Wan Jing , Li Long
Published: February 2021

Objective

We describe the clinical and genetic features, drug use and neuropsychiatric disorders of infants diagnosed with tuberous sclerosis complex (TSC) within 3 months of age at a neonatal intensive care unit (NICU) to better understand the different outcomes from early screening.

Methods

In this retrospective study, we consisted of 42 infants with a definitive TSC diagnosis by genetic criteria (TSC1 = 8, TSC2 = 34). The different phenotypes and outcomes between patients with TSC1 and TSC2 mutations were analyzed.

Results

The most common initial presenting features of TSC were cortical tubers on magnetic resonance imaging (50%), hypomelanotic macules on skin (47.61%) and spasm (42.85%), when they were diagnosed. Following disease progression to time of follow-up 1 year later, we found that the rate of epilepsy increased from 42.85% to 75.61% and that of cardiac rhabdomyoma increased from 28.57% to 43.9%. The median age at first presentation was 7.84 ± 1.88 months. We also found that 54.83% of patients on medication were seizure free for over 1 year, and that 43.9% of patients have intellectual disability. In total, 42 variants of TSC were detected, including 12 novel variants. We found no evidence of an association between different clinical features and their outcomes among patients with different gene mutations.

Conclusion

Early diagnosis of TSC in NICU opens a window of opportunity for early, more effective treatment of epilepsy as well as reduces the risk of neurological conditions.
Lack of Causal Effects or Genetic Correlation between Restless Legs Syndrome and Parkinson’s Disease
Authors: Estiar Mehrdad A , Senkevich Konstantin , Yu Eric , Varghaei Parizad , Krohn Lynne , Bandres-Ciga Sara , Noyce Alastair J , Rouleau Guy A , Gan-Or Ziv
Published: February 2021

Background

Epidemiological studies have reported association between Parkinson’s disease (PD) and restless legs syndrome (RLS).

Objectives

We aimed to use genetic data to study whether these two disorders are causally linked or share genetic architecture.

Methods

We performed two-sample Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC) using summary statistics from recent genome-wide meta-analyses of PD and RLS.

Results

We found no evidence for a causal relationship between RLS (as the exposure) and PD (as the outcome, inverse variance-weighted; b=-0.003, se=0.031, p=0.916, F-statistic=217.5). Reverse MR also did not demonstrate any causal effect of PD on RLS (inverse variance-weighted; b=-0.012, se=0.023, p=0.592, F-statistic=191.7). LDSC analysis demonstrated lack of genetic correlation between RLS and PD (rg=-0.028, se=0.042, p=0.507).

Conclusions

There was no evidence for a causal relationship or genetic correlation between RLS and PD. The associations observed in epidemiological studies could be, in part, attributed to confounding or non-genetic determinants.
RNA-binding proteins regulate aldosterone homeostasis in human steroidogenic cells
Authors: Fu Rui , Wellman Kimberly , Baldwin Amber , Rege Juilee , Walters Kathryn , Hirsekorn Antje , Riemondy Kent , Rainey William , Mukherjee Neelanjan
Published: February 2021

Angiotensin II (AngII) binds to the type I angiotensin receptor in the adrenal cortex to initiate a cascade of events leading to the production of aldosterone, a master regulator of blood pressure. Despite extensive characterization of the transcriptional and enzymatic control of adrenocortical steroidogenesis, there are still major gaps in our knowledge related to precise regulation of AII-induced gene expression kinetics. Specifically, we do not know the regulatory contribution of RNA-binding proteins (RBPs) and RNA decay, which can control the timing of stimulus-induced gene expression. To investigate this question, we performed a high-resolution RNA-seq time course of the AngII stimulation response and 4-thiouridine pulse labeling in a steroidogenic human cell line (H295R). We identified twelve temporally distinct gene expression responses that contained mRNA encoding proteins known to be important for various steps of aldosterone production, such as cAMP signaling components and steroidogenic enzymes. AngII response kinetics for many of these mRNAs revealed a coordinated increase in both synthesis and decay. These findings were validated in primary human adrenocortical cells stimulated ex vivo with AngII. Using a candidate siRNA screen, we identified a subset of RNA-binding protein and RNA decay factors that activate or repress AngII-stimulated aldosterone production. Among the repressors of aldosterone were BTG2, which promotes deadenylation and global RNA decay. BTG2 was induced in response to AngII stimulation and promoted the repression of mRNAs encoding pro-steroidogenic factors indicating the existence of an incoherent feedforward loop controlling aldosterone homeostasis. Together, these data support a model in which coordinated increases in transcription and regulated RNA decay facilitates the major transcriptomic changes required to implement a pro-steroidogenic gene expression program that is temporally restricted to prevent aldosterone overproduction.
Whole-genome analysis of antimicrobial-resistantEscherichia coliin human gut microbiota reveals its origin and flexibility in transmittingmcr-1
Authors: Ding Yichen , Saw Woei-Yuh , Tan Linda Wei Lin , Moong Don Kyin Nwe , Nagarajan Niranjan , Teo Yik Ying , Seedorf Henning
Published: February 2021

Multidrug resistant (MDR)Escherichia colistrains that carry extended-spectrum β-lactamases (ESBLs) or colistin resistance genemcr-1have been identified in the human gut at an increasing incidence worldwide. In this study, we sampled and characterized MDR Enterobacteriaceae from the gut microbiota of healthy Singaporeans and show that the prevalence of ESBL-producing andmcr-positive Enterobacteriaceae is 26.6% and 7.3%, respectively. Whole-genome sequencing of 37E. coliisolates identified 25 sequence types and assigned them into six different phylogroups, suggesting that the human intestinal MDRE. colistrains are highly diverse. In addition, we found thatE. coliisolates belonging to phylogroup D, B2 and F carry a higher number of virulence genes, whereas isolates of phylogroup A, B1 and E carry fewer virulence factor genes but are frequent carriers of florfenicol resistance genefloRand colistin resistance genemcr-1. Comparison of the sevenmcr-1-positiveE. coliisolates revealed thatmcr-1is carried by conjugative plasmids or embedded in composite transposons, which could potentially mobilizemcr-1to other pathogenic Enterobacteriaceae strains or MDR plasmids. Finally, we found that 12 out of the 37 MDRE. coliisolates in this study show high similarity to ESBL-producingE. coliisolates from raw meats from local markets, suggesting a potential transmission of MDRE. colifrom meat products to the human gut microbiota. Our findings show diverse antibiotic resistance and virulence profiles of intestinalE. coliand call for better countermeasures to block the transmission of MDRE. colivia the food chain.

Importance

The human gut can harbor both antibiotic resistant and virulentE. coliwhich may subsequently cause infections. In this study, the antibiotic resistance and virulence traits of antibiotic-resistantE. coliisolates from human gut microbiota of healthy subjects were investigated. The isolatedE. colistrains carry a diverse range of antibiotic resistance mechanisms and virulence factor genes, are highly diverse to each other, and are likely to originate from raw meat products from the local markets. Of particular concern are sevenE. coliisolates which carry colistin resistance genemcr-1. This gene can be mobilized into other pathogens and MDR plasmids, thereby spreading resistance to the last-resort antibiotic colistin. Our findings also suggest that raw meat could serve as important source to transmit MDR bacteria into the human gut microbiota.
Strategies to assure optimal trade-offs among competing objectives for genetic improvement of soybean
Authors: Ramasubramanian Vishnu , Beavis William
Published: February 2021

Plant breeding is a decision making discipline based on understanding project objectives. Genetic improvement projects can have two competing objectives: maximize rate of genetic improvement and minimize loss of useful genetic variance. For commercial plant breeders competition in the marketplace forces greater emphasis on maximizing immediate genetic improvements. In contrast public plant breeders have an opportunity, perhaps an obligation, to place greater emphasis on minimizing loss of useful genetic variance while realizing genetic improvements. Considerable research indicates that short term genetic gains from Genomic Selection (GS) are much greater than Phenotypic Selection (PS), while PS provides better long term genetic gains because PS retains useful genetic diversity during the early cycles of selection. With limited resources must a soybean breeder choose between the two extreme responses provided by GS or PS? Or is it possible to develop novel breeding strategies that will provide a desirable compromise between the competing objectives? To address these questions, we decomposed breeding strategies into decisions about selection methods, mating designs and whether the breeding population should be organized as family islands. For breeding populations organized into islands decisions about possible migration rules among family islands were included. From among 60 possible strategies, genetic improvement is maximized for the first five to ten cycles using GS, a hub network mating design in breeding populations organized as fully connected family islands and migration rules allowing exchange of two lines among islands every other cycle of selection. If the objectives are to maximize both short-term and long-term gains, then the best compromise strategy is similar except a genomic mating design, instead of a hub networked mating design, is used. This strategy also resulted in realizing the greatest proportion of genetic potential of the founder populations. Weighted genomic selection applied to both non-isolated and island populations also resulted in realization of the greatest proportion of genetic potential of the founders, but required more cycles than the best compromise strategy.
Cultivation-based quantification and identification of bacteria at two hygienic key sides of domestic washing machines
Authors: Jacksch Susanne , Zohra Huzefa , Weide Mirko , Schnell Sylvia , Egert Markus
Published: February 2021

Detergent drawer and door seal represent important sites for microbial life in domestic washing machines. Interestingly, quantitative data on microbial contamination of these sites is scarce. Here, 10 domestic washing machines were swap-sampled for subsequent bacterial cultivation at four different sampling sites, each: detergent drawer, detergent drawer chamber as well as top and bottom part of the rubber door seal. The average bacterial load over all washing machines and sites was 2.1 ± 1.0 × 104CFU cm−2(average ± standard error of the mean (SEM)). The top part of the door seal showed the lowest contamination (11.1 ± 9.2 × 101CFU cm−2), probably due to less humidity.

Out of 212 isolates, 178 (84%) were identified on genus level and 118 (56%) on species level using MALDI biotyping, resulting in 29 genera and 40 identified species across all machines. The predominant bacterial genera wereStaphylococcusandMicrococcus, which were found at all sites. 21 out of 40 species were classified as opportunistic pathogens, emphasizing the need for regular cleaning of the investigated sites.
Stable behavioral state-specific large scale activity patterns in the developing cortex of neonates
Authors: Mojtahedi Nima , Kovalchuk Yury , Böttcher Alexander , Garaschuk Olga
Published: February 2021

Endogenous neuronal activity is a hallmark of the developing brain. In rodents, a handful of such activities were described in different cortical areas but the unifying macroscopic perspective is still lacking. Here we combined large-scalein vivoCa2+imaging of the dorsal cortex in non-anesthetized neonatal mice with advanced mathematical analyses to reveal unique behavioral state-specific maps of endogenous activity. These maps were remarkably stable over time within and across experiments and used patches of correlated activity with little hemispheric symmetry as well as stationary and propagating waves as building blocks. Importantly, the maps recorded during motion and rest were almost inverse, with sensory-motor areas active during motion and posterior-lateral areas active at rest. The retrosplenial cortex engaged in both resting- and motion-related activities, building functional long-range connections with respective cortical areas. The data obtained bind different region-specific activity patterns described so far into a single consistent picture and set the stage for future inactivation studies, probing the exact function of this complex activity pattern for cortical wiring in neonates.
Quantitative Analysis of Plasmodesmata Permeability using Cultured Tobacco BY-2 Cells Entrapped in Microfluidic Chips
Authors: Shimizu Kazunori , Kikkawa Masahiro , Tabata Ryo , Kurihara Daisuke , Kurotani Ken-ichi , Honda Hiroyuki , Notaguchi Michitaka
Published: February 2021

Plasmodesmata are unique channel structures in plants that link the fluid cytoplasm between adjacent cells. Plants have evolved these microchannels to allow trafficking of nutritious substances as well as signaling molecules for intercellular communication. However, tracking the behavior of plasmodesmata in real time is difficult because they are located inside tissues. Hence, we developed a microfluidic device that traps cultured cells and fixes their positions to allow testing of plasmodesmata permeability. The device has 112 tandemly aligned trap zones in the flow channel. Cells of the tobacco line BY-2 were cultured for 7 days and filtered using a sieve and a cell strainer before use to isolate short cell clusters consisting of only a few cells. The isolated cells were introduced into the flow channel, resulting in entrapment of cell clusters at 25 out of 112 trap zones (22.3%). Plasmodesmata permeability was tested from 1 to 4 days after trapping the cells. During this period, the cell numbers increased through cell division. Fluorescence recovery after photobleaching experiments using a transgenic marker line expressing nuclear-localized H2B-GFP demonstrated that cell-to-cell movement of H2B-GFP protein occurred within 200 min of photobleaching. The transport of H2B-GFP protein was not observed when sodium chloride, a compound known to cause plasmodesmata closure, was present in the microfluid channel. Thus, this microfluidic device and one-dimensional plant cell samples allowed us to observe plasmodesmata behavior in real time under controllable conditions.
Optimizing EEG source reconstruction with concurrent fMRI-derived spatial priors
Authors: Abreu Rodolfo , F. Soares Júlia , Batista Sónia , Cláudia Lima Ana , Sousa Lívia , Castelo-Branco Miguel , Duarte João Valente
Published: February 2021

Reconstructing EEG sources involves a complex pipeline, with the inverse problem being the most challenging. Multiple inversion algorithms are being continuously developed, aiming to tackle the non-uniqueness of this problem, which has been shown to be partially circumvented by also including fMRI-derived spatial priors in the inverse models. However, only task activation maps and resting-state networks (RSNs) have been explored so far, overlooking the recent, but already accepted, notion that brain networks exhibit dynamic functional connectivity (dFC) fluctuations. Moreover, there is no consensus regarding the inversion algorithm of choice, nor a systematic comparison between different sets of spatial priors. Using simultaneous EEG-fMRI data, here we compared four different inversion algorithms (MN, LORETA, EBB and MSP) under a Bayesian framework, each with three different sets of priors consisting of: 1) those specific to the algorithm (S1); 2) S1plus fMRI task activation maps and RSNs (S2); and 3) S2plus network modules of task-related dFC states estimated from the dFC fluctuations (S3). The quality of the reconstructed EEG sources was quantified in terms of model-based metrics, namely the free-energy and variance explained of the inversion models, and the overlap/proportion of brain regions known to be involved in the visual perception tasks that the participants were submitted to, and RSN templates, with/within EEG source components. Model-based metrics suggested that model parsimony is preferred, with the combination MSP+S1exhibiting the best performance. However, optimal overlap/proportion values were found using EBB+S2or MSP+S3, respectively, indicating that fMRI spatial priors, including dFC state modules, are crucial for the EEG source components to reflect neuronal activity of interest. Our results pave the way towards a more informative selection of the optimal EEG source reconstruction approach, which may be crucial in future studies.
Rules for the self-assembly of ESCRT-III on endosomes
Authors: Sprenger Simon , Migliano Simona M. , Oleschko Florian , Kobald Marvin , Hess Michael , Teis David
Published: February 2021

We, the authors, have withdrawn this manuscript. During our work on the revision of this manuscript for eLife, it became clear that several key results of the manuscript were not reproducible by my lab. The rules for ESCRT-III assembly and the model that we have proposed in this manuscript are no longer supported by the data. Currently we are performing additional experiments to test some of our conclusions further. Therefore, we do not wish this work to be cited.

We sincerely apologize to the scientific community for any inconvenience resulting from this manuscript.

If you have any questions, please contact the corresponding author.
Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma
Authors: Ray Arja , Callaway Mackenzie K. , Rodríguez-Merced Nelson J. , Crampton Alexandra L. , Carlson Marjorie , Emme Kenneth B. , Ensminger Ethan A. , Kinne Alexander A. , Schrope Jonathan H. , Rasmussen Haley R. , Jiang Hong , Denardo David G. , Wood David K. , Provenzano Paolo P.
Published: February 2021

Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here in both murine and human PDA we demonstrate that extracellular matrix architecture regulates cell extrusion and subsequent invasion from intact ductal structures through Tumor-Associated Collagen Signatures (TACS), resulting in early dissemination from histologically pre-malignant lesions and continual invasion from well-differentiated disease. Furthermore, we show that pancreatitis results in invasion-conducive architectures, thus priming the stroma prior to malignant disease. Analysis in novel microfluidics-derived microtissues andin vivodemonstrates decreased extrusion and invasion following focal adhesion kinase (FAK) inhibition, consistent with decreased metastasis. Thus, data suggest that targeting FAK or strategies to re-engineer and normalize tumor microenvironments, may have a role not only in also in very early disease but also for limiting continued dissemination from unresectable disease. Likewise, it may be beneficial to employ stroma targeting strategies to resolve precursor diseases such as pancreatitis in order to remove stromal architectures that increase risk for early dissemination.

Impact Statement

Collagen architectures in the tumor stroma facilitate dissemination of carcinoma cells from the earliest histologically “pre-malignant” lesions and continue to promote disease spread from well-differentiated PDA.
A self-templated route to monodisperse complex droplets as artificial extremophile-mimic from coacervate-liposome interplay
Authors: Li Qingchuan , Song Qingchun , Guo Wei , Cao Yang , Chao Youchuang , Cui Xinyu , Wei Jing , Chen Dairong , Shum Ho Cheung
Published: February 2021

Bottom-up synthetic biology seeks to construct artificial cells from simple building blocks for exploring origin and principles of cellular life and material design. Although cellular life may have emerged spontaneously, programmable integration of building blocks into size, membrane property-controlled compartments (liposome or coacervate) towards cellular organization, without using specialized devices, has proven difficult. Here, we report a self-templated route to monodisperse complex droplets in bulk solution from coacervate-liposome synergy, with nanoliposome controlling coacervate size and coacervate templating on-surface nanoliposome fusion. Nanoliposome-coated monodisperse coacervates are self-assembled within 30 seconds, which are sealed by fusing nanoliposomes into size-controlled giant unilamellar vesicles (GUVs), with model building blocks combinatorially integrated into droplets. Defect-free membrane is established on coacervate, which render these complex GUVs surviving at extreme osmotic, salty and pH conditions (4 M NaCl, 100 mM HCl, 1 M NaOH), while providing homeostasis for enzymatic reactions, reminiscent of extremophiles.
Structural connectome fingerprinting and age prediction in pediatric development: assessing voxel- and surface-based white matter connectivity
Authors: Al-Sharif Noor B , St-Onge Etienne , Vogel Jacob W , Descoteaux Maxime , Evans Alan C
Published: February 2021

Mapping structural white matter connectivity is a challenge, with many barriers to accurate representation. Here, we assessed the replicability and reliability of two connectome-generating methods, voxel- or surface-based, using test-retest analyses, fingerprinting and age prediction. The two connectomic methods are initiated by the same state-of-the-art dMRI processing pipeline before diverging at the tractography and connectome-generating steps using either voxels or surfaces. While both methods performed very well across all analyses, voxel-based connectomes performed marginally better than surface-based connectomes. Notably, structural connectomes derived from either method demonstrate reliably accurate representations of both individuals and their chronological age, comparable to similar analyses employing multi-modal features. The difference in methodological performance could be attributed to a number of method-specific features but ultimately show that cutting-edge tractography with robust dMRI processing produces reliable white matter connectivity measures.
Paradoxical Roles of Peritumoral Myofibroblasts in Intrahepatic Cholangiocarcinoma Growth and Metastasis
Authors: Tian Cheng , Li Liyuan , Li Yizhen , Fan Li , Brown Anthony , Morrison Michelle , Norris Eric J. , Yang Jun J. , Glazer Evan S. , Zhu Liqin
Published: February 2021

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive type of primary liver cancer characterized by its highly desmoplastic stroma. Compared to the ample knowledge on cancer-associated fibroblast residing within iCCA tumor mass, little is known about the fibrotic response from the tumor-surrounding liver and its role in iCCA development. In this study, we find a significant accumulation of peritumoral myofibroblasts (pMFs) in both patient iCCA and tumors from an iCCA orthotopic allograft mouse model. Using tumor and liver spheroid coculture we show that iCCA-liver interaction induces rapid pMF accumulation at the interface. We find pMFs placed around iCCA spheroids exert a strong suppressive effect on tumor cells growth, in contrast to the pro-proliferative effect of MFs mixed within tumor spheroids. However, prolonged iCCA-pMF interaction elicits tumor cell dissemination in vitro. We find an upregulation of Vcam1 in tumor cells in the early phase of iCCA-pMF interaction both in vitro and in vivo which is downregulated when tumor cells disseminate. Blocking Vcam1 activity in iCCA allograft mouse models slows primary tumor growth but lead to increased tumor metastasis. Our data suggest that pMFs are beyond simple pro- or anti-tumorigenic in iCCA, with the ability to suppress tumor growth but elicit tumor cell dissemination.
Long-term association of pregnancy and maternal brain structure: the Rotterdam Study
Authors: Aleknaviciute Jurate , Evans Tavia E. , Aribas Elif , de Vries Merel W. , Steegers Eric A.P. , Ikram M. Arfan , Tiemeier Henning , Kavousi Maryam , Vernooij Meike W. , Kushner Steven A.
Published: February 2021

The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women’s lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of parity on maternal brain structure remain unknown. Therefore, we utilized a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (β= 0.14, 95% CI = 0.09-0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings indicate that pregnancy and childbirth are associated with robust long-term changes in brain structure involving larger global gray matter volume that persists for decades. Taken together, these data provide novel insight into the impact of motherhood on the human brain.
Environmental DNA in a Global Biodiversity Hotspot: Lessons from Coral Reef Fish Diversity Across the Indonesian Archipelago
Authors: Marwayana Onny N. , Gold Zachary , Barber Paul H.
Published: February 2021

Indonesia is the heart of the Coral Triangle, the world’s most diverse marine ecosystem. Preserving the biological and economic value of this marine biodiversity requires efficient and economical ecosystem monitoring, yet our understanding of marine biodiversity in this region remains limited. This study uses environmental DNA (eDNA) to survey fish communities across a pronounced biodiversity gradient in Indonesia. A total of 12,939,690 sequence reads of MiFish12SrRNA from 39 sites spanning 7 regions of Indonesia revealed 4,146 Amplified Sequence Variants (ASVs). Regional patterns of fish diversity based on eDNA broadly conformed to expectations based on traditional biodiversity survey methods, with the highest fish biodiversity in Raja Ampat and generally lower diversity in Western Indonesia. However, eDNA performed relatively poorly compared to visual survey methods in site-by-site comparisons, both in terms of total number of taxa recovered and ability to assign species names to ASVs. This result stands in a stark contrast to eDNA studies of temperate and tropical ecosystems with lower diversity. Analyses show that while sequencing depth was sufficient to capture all fish diversity within individual seawater samples, variation among samples from individual localities was high, and sampling effort was insufficient to capture all fish diversity at a given sampling site. Interestingly, mean ASVs recovered per one-liter seawater was surprisingly similar across sites, despite substantial differences in total diversity, suggesting a limit to total ASVs (~200) per one-liter eDNA sample. Combined, results highlight two major challenges of eDNA in highly diverse ecosystems such as the Coral Triangle. First, reference databases are incomplete and insufficient for effective ASV taxonomic assignment. Second, eDNA sampling design developed from lower diversity temperate marine ecosystems are inadequate to fully capture diversity of biodiversity hotspots like the Coral Triangle.
VAMP2 AND SYNAPTOTAGMINS ARE RELATIVELY IMMOBILE ON CHROMAFFIN GRANULE MEMBRANES: IMPLICATIONS FOR MEMBRANE FUSION AND FUSION PORE EXPANSION
Authors: Abbineni Prabhodh S. , Briguglio Joseph S. , Chapman Edwin R. , Holz Ronald W. , Axelrod Daniel
Published: February 2021

Although many of the proteins of secretory granules have been identified, little is known about their molecular organization and diffusion characteristics. Granule-plasma membrane fusion can only occur when proteins that enable fusion are present at the granule-plasma membrane contact. Thus, the mobility of granule membrane proteins may be an important determinant of fusion pore formation and expansion. To address this issue, we measured the mobility of (fluorophore-tagged) vesicle associated membrane protein 2 (VAMP2), synaptotagmin 1 (Syt1), and synaptotagmin 7 (Syt7) in chromaffin granule membranes in living chromaffin cells. We used a method that is not limited by standard optical resolution. A bright flash of strongly decaying evanescent field (∼80 nm exponential decay constant) produced by total internal reflection (TIR) was used to photobleach GFP-labeled proteins in the granule membrane. Fluorescence recovery occurs as unbleached protein in the granule membrane distal from the glass interface diffuses into the more bleached proximal regions, thereby enabling the measurement of diffusion coefficients. The studies revealed that VAMP2, Syt1, and Syt7 are relatively immobile in chromaffin granules membranes with diffusion constants of ≤ 3 × 10−10 cm2/s. Utilizing these diffusion parameters and the known density of VAMP2 and Syt 1 on synaptic vesicles, we estimated the time required for these proteins to arrive at a nascent fusion site to be tens of milliseconds. We propose that the mobilities of secretory granule SNARE and Syt proteins, heretofore unappreciated factors, influence the kinetics of exocytosis and protein discharge.

Significance Statement

In eukaryotic cells, secretory vesicles fuse with the plasma membrane to secrete chemical transmitters, hormones and proteins that enable diverse physiological functions including neurotransmission. Fusion proteins need to be assembled at the fusion site in sufficient number in order to enable membrane fusion. However, the diffusion characteristics of fusogenic proteins on secretory vesicles remained unknown. Here we used a novel method not limited by standard optical resolution to measure the diffusion of VAMP2 and synaptotagmins on chromaffin granule membranes. We found they have limited mobility. The time required for these proteins to reach the granule-plasma membrane contact site suggests that their limited mobility likely influences the kinetics of membrane fusion and subsequent fusion pore expansion.
Corrosion mechanism of a new-type low-alloy corrosion resistant steel containing Sb used in acid environment
Authors: Yang Ying , Wu Wei , Cheng Xuequn , Zhao Jinbin , Zhaoal Baijie , Li Xiaogang
Published: February 2021

Purpose

This study aims to develops a new-type low-alloy corrosion resistant steel containing Sb and investigate the corrosion mechanism of this new-type low-alloy steel.

Design/methodology/approach

Energy dispersive spectrometer, X-ray photoelectron spectroscopy, X-Ray diffraction and scanning electron microscopy were used to evaluate the corrosion resistance of the rust layers formed on these samples. Laser confocal microscopy was used to observe the corroded surfaces of the steels.

Findings

Results showed that Sb added can consume H+ in the solution, thereby preventing the oxygen reaction to slow down the corrosion rate. Meanwhile, a stable and insoluble substance (Sb2O3) in the acidic solution would be produced when the reaction of the product of Sb and H+ with the enough dissolved oxygen in the solution. Due to the precipitation of Sb2O3 and iron oxyhydroxides, the rust layer of Sb-containing steel became more uniform and compact, which resulted in better corrosion resistance in acid environment.

Originality/value

In this study, a new-type acid resistant low-alloy steel containing Sb was developed. Compared with the results, the corrosion mechanism of the new-type low-alloy steel in acid environment was discussed.
The costs of COVID-19 and the cost-effectiveness of testing
Authors: González López-Valcárcel Beatriz , Vallejo-Torres Laura
Published: February 2021

Purpose

This paper aims to provide an estimation of the costs of the coronavirus (COVID-19) pandemic with a special focus on Spain. Costs include macroeconomic costs of foregone gross domestic product (GDP) attributable to the pandemic and the direct and indirect costs of prevention, treatment and lost productivity. This study also analyzes the cost-effectiveness of the test-tracking-quarantine (TTQ) strategy in Spain.

Design/methodology/approach

The macroeconomic costs of foregone GDP attributable to the pandemic are estimated for different countries and areas by comparing the present GDP forecasts for 2020 and 2021 with counterfactuals estimated before the COVID-19 crisis aftermath. The total cost of the COVID-19 for Spain in 2020 was obtained using the cost of illness approach with a bottom-up process. A cost-effectiveness analysis of the TTQ strategy in Spain is based on the estimation of the total costs of TTQ and the health gains and avoided health-care costs associated with the TTQ strategy. A sensitivity analysis explores the consequences of uncertainty in key parameters.

Findings

The GDP cost of the COVID-19 is by far larger than all the other components of the cost. The global cost of the Covid-19 crisis in 2020–2021 is estimated at 14% of 2019 GDP (around 12,206 mm$). In the specific case of Spain, it amounts to 24% of the 2019 GDP; which is 397.3 m €. Spain is and will be by far the European country most economically affected by the pandemic. In Spain 2020, the GDP cost accounts for 94.7% of the total cost of the COVID-19 and health-care direct costs are only 2.14%. TTQ is a dominant strategy in Spain. For each euro spent on it, 7 euros will be recovered only in terms of saved health-care resources.

Research limitations/implications

Given the large degree of uncertainty and the fast-evolving nature of the epidemic, a number of assumptions are required to arrive at the estimates provided in this study. The results were found to be robust to the assumptions applied.

Practical implications

TTQ is a key strategy for the contention of the epidemy and it is justified from the economic perspective.

Originality/value

This is the first estimation of the cost of the COVID-19 and the cost-effectiveness of the TTQ strategy for Spain.
Proposed guidelines for treatment of recurrent failures for sustainability of results in the post-project improvement stage process
Authors: Almeida Caio Melo , Araujo Fernando Oliveira , Abreu Chrystyane Gerth Silveira , Batista Haydee Maria Correia da Silveira
Published: February 2021

Purpose

The maintenance of process improvement programs within organizations is not an easy task. Some processes do not maintain the results achieved with the improvement project and again present low performance shortly after completion of the project. This paper aims to identify the socio-technical causes responsible for the loss of process performance after applying improvement projects, in order to support the mitigation of the problem.

Design/methodology/approach

A systematic review of the literature was carried out, which allowed the selection of 28 articles. The empirical stage used the benchmarking technique, along a large Brazilian mining company with an international standard of production and quality. This organization has been using improvement projects for more than ten years.

Findings

The research complements the literature regarding the prioritization of the 26 identified failures and the identification of seven new failure factors and two resources. Findings in this study can be an inspiration for other organizations, considering the similarity of methodological aspects of improvement projects since internationally standardized methodologies such as Six Sigma, Lean, Kaizen and 5S are used.

Originality/value

The research presented a proposal of guidelines that corroborate to the mitigation of loss of process performance after improvement project.
Voremetur Project: proposal for the digital cataloguing of museum objects on media art
Authors: García-López Fátima , Martínez-Cardama Sara , Morales-García Ana María
Published: February 2021

Purpose

The purpose of this paper is to describe the creation of a catalogue of museum objects associated with two media art collections. The proposal was formulated under the Voremetur Project “Vocabularios para una Red de Archivos y Colecciones de Media Art y sus efectos: metaliteracy y turismo de conocimiento” (thesauri for networked media art archives and collections and their effects: metaliteracy and knowledge tourism) (HAR2016-75949-C2-1-R). Collection characteristics and typologies are discussed along with the difficulties encountered and the interoperability of the platform chosen with other Web resources that foster visibility.

Design/methodology/approach

This paper describes a case study and a review of the protocols and standards used to catalogue media art collections. Digitised descriptions were processed with Omeka software in conjunction with the expanded Dublin Core metadata schema. This paper also reviews the literature on the conceptualisation of these collections and the challenges involved in their conservation and management.

Findings

The result was the creation of a digital repository for two media art collections: one linked to Espacio P; and the other the outcome of digitising part of the MIDECIANT collection (Archivo Media ART AEMA).

Originality/value

The methodology innovates the description and analysis of museum objects on media art in Spain. The proposed cataloguing method can be replicated and used to describe similar collections and lays the grounds for creating a Spanish network of media art archives and collections.