bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical analysis of an integrated solar cell and a photon up converter, providing guidance for future device engineering efforts
Authors: Hamzawy Sameh , Wagner Pawel , Gallaher Joseph K. , Schmidt Timothy W. , Mozer Attila J. , Nattestad Andrew
Published: November 2021

To date, a number of photon up-conversion (UC) systems with high quantum efficiencies have been demonstrated, including at non-concentrated solar illumination intensities. These are, however, yet to be successfully combined with photovoltaic devices in order to provide substantial increases in photocurrent, as compared with devices without UC. In the present work, we perform simple calculations, based on the optical properties of an UC + solar cell system, specifically a dye-sensitized solar cell and sensitized-triplet-triplet annihilation based UC system, in line with our previous experimentally realized proof-of-concept devices. This model is then used to more specifically identify the limitations and losses, thereby providing a pathway toward improvements, based on either real or hypothetical materials. This model highlights that only a fraction of the benefit may be realized without substantial improvements being made in terms of various transmission losses, coupled with the fact that UC emission typically scales quadratically in this flux regime. The model presented can help identify where research efforts should be focused as well as where there may be little utility, with these lessons also being valuable in the future as even more efficient UC systems are developed. Furthermore, a spreadsheet is provided in the supplementary material to assist other researchers in their efforts.
The diversity of plant species used in traditional herbal massage oil in Indonesia
Authors: Rahayu Mulyati , Susan Dewi , Keim Ary Prihardhyanto , Susiarti Siti , Sujarwo Wawan
Published: November 2021

Context The Austronesian peoples, predecessors of most of the population of Indonesia today, discovered and developed many kinds of plant-based medicines and treatments to combat illness and maintain good health. These include massage oils. Aims This study investigated how three tribal communities in Indonesia utilised plants for massage oils with the aim of preserving their traditional methods. Methods Traditional plant-based massage oils used by the western–central Austronesians were studied in three traditional communities in West Java, Lombok Island and Sumbawa Island. Key results Traditional herbal oils contain various active compounds that possess medicinal values. Coconut (Cocos nucifera; Arecaceae), which is typical of Austronesian flora, is harvested for milk and is the main ingredient in the production of herbal treatments for massages. Forty-six other plant species have also been recorded being mixed with coconut milk. The main three families of plants are: Fabaceae, Lauraceae and Zingiberaceae. Species such as Dipterocarpus retusus (endangered) and Sindora galedupa are medicinal plants with high conservation value. Conclusions Changes in land use threaten wild plant species that are used in making herbal oils. Likewise, traditional community knowledge could be eroded by globalisation. Therefore, the cultivation and conservation of wild plants is needed to maintain their presence in nature so that the traditional knowledge can be sustained. Implications Local governments need to play a role in developing and socialising the use of traditional herbal massage oils. It is hoped that the traditional knowledge and wisdom of the local communities can form the basis of developing their territory into a traditional village, like the village of Songak, Lombok Island.
Cover crop residue diversity enhances microbial activity and biomass with additive effects on microbial structure
Authors: Shu Xin , Zou Yiran , Shaw Liz J. , Todman Lindsay , Tibbett Mark , Sizmur Tom
Published: November 2021

Context Cover crops are used to improve soil fertility and environmental sustainability. Decomposition of cover crop residues can affect belowground microbial communities and activity, which is important for soil functions (e.g. nutrient cycling, organic matter decomposition). Aims We investiagated the effect of plant residues from a range of cover crop species on soil microbial activity, diversity and microbial community composition. Methods A mixture of four cover crop residues (buckwheat, clover, sunflower, radish) or an equal mass of the residues of each of the individual species were assessed for their effect on soil respiration and soil microbial community structure. Key results Cover crop residue incorporation significantly (P < 0.001) increased soil respiration during 84 days incubation and this response caused a significant change in microbial community composition by increasing the proportion of fungi and Gram-positive bacteria at the cost of decreasing Gram-negative bacteria. The mixture of cover crop residues had a significantly (P < 0.05) greater soil respiration rate, by 57.61 μg C g−1 h−1, than the average of the four individual residues, but did not have a significantly different soil microbial biomass or microbial community structure. Conclusions Greater diversity of organic resources increased the number biochemical niches, and activated dormant microbial communities to increase activity without affecting biomass or community composition. Greater respiration from similar microbial biomasses suggests that microbial activity might be more efficient following more diverse substrate input. Implications The positive impact of cover crop residues on soil microbial activity suggests that mixtures of cover crop residues may enhance soil functions beyond the sum of individual cover crop residues.
-ŋ plurals in North Lombard varieties
Authors: Manzini Maria Rita , Savoia Leonardo M. , Baldi Benedetta
Published: November 2021

We focus on North Lombard -a and -n feminine plurals, for which we provide a morphological analysis. At the syntactic level, the relevant varieties are characterized by the phenomenon of Differential Plural Marking, whereby phasal domains have different realizations of plural morphology on the head of the phase and on the complement of the phase. We provide an account of DPM based on the assumption that under the PIC the complement of the phase and its head are externalized separately. We draw consequences concerning clitics as phasal heads as well as object agreement with participles and with finite verbs.
Aspect in the acquisition of the Spanish locative paradigm by Italian L2 learners
Authors: Perpiñán Silvia , Marín Rafael
Published: November 2021

The present study investigates the development of the expression of the locative paradigm in the L2 Spanish of Italian-speaking learners. We investigate (i) whether the developmental stages proposed for English-speaking learners (VanPatten 1987; Perpiñán, Marín & Moreno Villamar 2020) hold for Italian-speaking learners; and (ii) whether Italian, a language that partially overlaps with the distribution of the Spanish copulas has a facilitative role in the process. 33 Italian-speaking learners of Spanish and 21 monolingual Spanish speakers completed a short proficiency test, an acceptability judgement task, and a picture matching task targeting these constructions. Results indicate that unlike what VanPatten (1987, 2010) has proposed for English-speaking learners of Spanish, Italian speakers do not present a delay in the acquisition of estar, but instead, it is overproduced in locative contexts from very early on. We argue that this overproduction of estar is due to the readily available mapping of ‘temporal boundedness’ with estar in the grammar of these L2 learners, whereas the presence of the feature ‘dynamicity’, even though it is relevant in the distribution of copulas in Italian, comes later in L2 development.
Catalan nativization patterns in the light of weighted scalar constraints
Authors: Pons-Moll Claudia , Torres-Tamarit Francesc
Published: November 2021

In this paper we analyze, from an experimental and formal perspective, the interaction and the implicational relationships between vowel reduction and word-final nasal deletion in Catalan loanwords. We present the results of both a production and a perception test carried out with 31 young speakers from the Barcelona area. Loanwords susceptible to undergoing both nasal deletion and vowel reduction display different patterns, which, according to the tests, show different degrees of likeliness. The most common pattern is underapplication of both processes, followed closely by underapplication of nasal deletion alone and at a large distance by the application of both processes. Finally, underapplication of vowel reduction and application of nasal deletion is unattested in the production test and obtains a very low score in the perception test, that is, it is a very unlikely nativization pattern. The typology of possible nativizations and the implicational relationships between the processes under scrutiny are analyzed in the framework of Harmonic Grammar under Weighted Scalar Constraints, following recent proposals by Hsu & Jesney (2017, 2018).
High-throughput single-cell epigenomic profiling by targeted insertion of promoters (TIP-seq)
Authors: Bartlett Daniel A. , Dileep Vishnu , Handa Tetsuya , Ohkawa Yasuyuki , Kimura Hiroshi , Henikoff Steven , Gilbert David M.
Published: November 2021

Chromatin profiling in single cells has been extremely challenging and almost exclusively limited to histone proteins. In cases where single-cell methods have shown promise, many require highly specialized equipment or cell type–specific protocols and are relatively low throughput. Here, we combine the advantages of tagmentation, linear amplification, and combinatorial indexing to produce a high-throughput single-cell DNA binding site mapping method that is simple, inexpensive, and capable of multiplexing several independent samples per experiment. Targeted insertion of promoters sequencing (TIP-seq) uses Tn5 fused to proteinA to insert a T7 RNA polymerase promoter adjacent to a chromatin protein of interest. Linear amplification of flanking DNA with T7 polymerase before sequencing library preparation provides ∼10-fold higher unique reads per single cell compared with other methods. We applied TIP-seq to map histone modifications, RNA polymerase II (RNAPII), and transcription factor CTCF binding sites in single human and mouse cells.
Effect of annealing temperature and time on recrystallization behavior of Mg-Gd-Y-Zn-Zr alloy
Authors: Han Rui , Jia Leichen , Zhang Zhimin , Wang Qiang , Yu Jianmin , Xu Jian , Xue Yong
Published: November 2021

In this paper, the effect of annealing treatment on the microstructure and hardness of extruded Mg-9Gd-4Y-2Zn-0.5Zr alloy (wt. %) was discussed. The microstructure evolution of the alloy under different annealing conditions was studied by optical microscope (OM), scanning electron microscopy (SEM) and electron backscatter diffraction (EBSD), and the variation of hardness was analyzed. With the increase of annealing temperature, the large deformed grains first break into small recrystallized grains. When the temperature continues to increase, the recrystallized grains grow abnormally with the precipitation of chain phase and the fragmentation of lamellar long-period stacking ordered (LPSO) phase. The alloy does not recrystallize at low temperature, and the recrystallize grains grow abnormally at high temperature. The increase of annealing time will also lead to abnormal growth of recrystallized grains. The texture gradually diffuses from the classical extrusion texture to the extrusion direction (ED). The results show that under the condition of 430 °C × 5 h, the recrystallization volume of the alloy is the largest, the recrystallization grain distribution is uniform, and the hardness value is the highest.
3D-bioprinted microenvironments for sweat gland regeneration
Authors: Song Wei , Yao Bin , Zhu Dongzhen , Zhang Yijie , Li Zhao , Huang Sha , Fu Xiaobing
Published: November 2021

The development of 3D bioprinting in recent years has provided new insights into the creation of in vitro microenvironments for promoting stem cell-based regeneration. Sweat glands (SGs) are mainly responsible for thermoregulation and are a highly differentiated organ with limited regenerative ability. Recent studies have focused on stem cell-based therapies as strategies for repairing SGs after deep dermal injury. In this review, we highlight the recent trend in 3D bioprinted native-like microenvironments and emphasize recent advances in functional SG regeneration using this technology. Furthermore, we discuss five possible regulatory mechanisms in terms of biochemical factors and structural and mechanical cues from 3D bioprinted microenvironments, as well as the most promising regulation from neighbor cells and the vascular microenvironment.
Left ventricular shape predicts arrhythmic risk in fibrotic dilated cardiomyopathy
Authors: Balaban Gabriel , Halliday Brian P , Hammersley Daniel , Rinaldi Christopher A , Prasad Sanjay K , Bishop Martin J , Lamata Pablo
Published: November 2021

Aims

Remodelling of the left ventricular (LV) shape is one of the hallmarks of non-ischaemic dilated cardiomyopathy (DCM) and may contribute to ventricular arrhythmias and sudden cardiac death. We sought to investigate a novel three dimensional (3D) shape analysis approach to quantify LV remodelling for arrhythmia prediction in DCM.

Methods and results

We created 3D LV shape models from end-diastolic cardiac magnetic resonance images of 156 patients with DCM and late gadolinium enhancement (LGE). Using the shape models, principle component analysis, and Cox-Lasso regression, we derived a prognostic LV arrhythmic shape (LVAS) score which identified patients who reached a composite arrhythmic endpoint of sudden cardiac death, aborted sudden cardiac death, and sustained ventricular tachycardia. We also extracted geometrical metrics to look for potential prognostic markers. During a follow-up period of up to 16 years (median 7.7, interquartile range: 3.9), 25 patients met the arrhythmic endpoint. The optimally prognostic LV shape for predicting the time-to arrhythmic event was a paraboloidal longitudinal profile, with a relatively wide base. The corresponding LVAS was associated with arrhythmic events in univariate Cox regression (hazard ratio = 2.0 per quartile; 95% confidence interval: 1.3–2.9), in univariate Cox regression with propensity score adjustment, and in three multivariate models; with LV ejection fraction, New York Heart Association Class III/IV (Model 1), implantable cardioverter-defibrillator receipt (Model 2), and cardiac resynchronization therapy (Model 3).

Conclusion

Biomarkers of LV shape remodelling in DCM can help to identify the patients at greatest risk of lethal ventricular arrhythmias.
Effectiveness of non-opioid interventions to reduce opioid withdrawal symptoms in patients with chronic pain: a systematic review
Authors: Langejan Annely I , de Kleijn Loes , Rijkels-Otters Hanneke J B M , Chudy Stan F J , Chiarotto Alessandro , Koes Bart W
Published: November 2021

Background

Dealing with the opioid crisis, medical doctors are keen to learn how to best treat opioid dependency in patients with chronic non-cancer pain. Opioid replacement therapy is commonly used, but success rates vary widely. Since many patients still experience severe withdrawal symptoms, additional interventions are necessary.

Objective

To review the effectiveness of interventions in the treatment of withdrawal symptoms during opioid tapering or acute withdrawal in patients with long-term non-cancer pain.

Methods

A systematic review was conducted in Embase.com, MEDLINE, Web of Science, PsycINFO, and Cochrane CENTRAL register of trials. Studies eligible for inclusion were (non-)randomized controlled trials in adults with long-term opioid prescriptions for non-cancer pain. Included trials had to compare a non-opioid intervention to placebo, usual care, no treatment, or non-opioid drug and had to report on withdrawal symptoms as an outcome. Study quality was assessed with the 2.0 Cochrane risk of bias (RoB) tool. Evidence quality was rated following the GRADE approach.

Results

One trial (n = 21, some concerns regarding RoB) compared Varenicline to placebo. There was no statistically significant between-group reduction of withdrawal symptoms (moderate-quality evidence).

Conclusions

Evidence from clinical trials on interventions reducing withdrawal symptoms is scarce. Based on one trial with a small sample size, no firm conclusion can be drawn. Meanwhile, doctors are in dire need for therapeutic options to tackle withdrawal symptoms while tapering patients with prescription opioid dependence. We hope this review draws attention to this unfortunate research gap so that future research can provide doctors with answers.
Narratives Beyond books: Artistic Agency and Encounter with an Audience in the Work of the Compagnia delle poete and Gabriella Ghermandi
Authors: Panzarella Gioia
Published: November 2021

Building on recent critical contributions on contemporary transnational literature in the Italian language, this article explores the link between the literary production of the artist Gabriella Ghermandi and the Compagnia delle poete – a collective of 20 female artists from different countries – and some of their respective performances. I argue that these performances reduce the space for interventions by the cultural intermediaries involved in the organization of events aimed at disseminating the Compagnia’s and Ghermandi’s literary production: the performances constitute new interzonal artistic explorations and preserve the agency of the artists when presenting their narrative around their own literary production; they emphasize the element of collaboration and can be discussed as part of a process of self-translation. This article pays particular attention to the prominence of the theme of migration in public discourse in Italy, which has provided opportunities for writers and artists with an interest in migration to take part in cultural events.
Understanding the complexity of demand-side determinants on vaccine uptake in sub-Saharan Africa
Authors: van Heemskerken Phylisha G , Decouttere Catherine J , Broekhuizen Henk , Vandaele Nico J
Published: November 2021

Routine vaccination annually prevents millions of deaths worldwide but is underutilized in sub-Saharan Africa (SSA). The complexity of socio-cultural factors impacting vaccine uptake is not well understood. Hence, this paper aims to review the socio-cultural determinants of vaccine uptake and visualize their interrelationships. We conducted a literature search using Pubmed and Embase databases, including articles published from 2000 to 2019 describing socio-cultural demand-side determinants for vaccine uptake. Using the Andersen and Newman Framework of Health Services Utilization, demand-side determinants were categorized as predisposing, enabling or need factors. A qualitative system dynamics approach was employed to visualize how these factors and their dynamic interrelationships influence vaccine uptake. This visualization, by means of a causal-loop diagram (CLD), was mostly based on a qualitative input, with the majority being statements of the authors. These statements were abstracted from the papers found in the review. Quantification was done by counting direct (statistical) associations between each determinant and ‘timely and full routine immunization coverage’. A total of 90 articles, primarily from Nigeria (n = 23), Ethiopia (n = 17) and Kenya (n = 11), met the inclusion criteria. We find that maternal autonomy and the perceived benefits caregivers attach to vaccination and exert their influences on many other factors through several feedback loops, thereby influencing timely and full routine immunization coverage. Utilization of health services (supply-related) and access to information (demand-related) were considered as high-potential leverage points. Quantification has shown that maternal autonomy and perceived benefit have an unclear evidence base. Future research should focus on these key players as they play a central role in multiple complex pathways, through which they could influence the uptake of vaccines in SSA.
Mitochondrial genome-wide analysis of nuclear DNA methylation quantitative trait loci
Authors: Laaksonen Jaakko , Mishra Pashupati P , Seppälä Ilkka , Raitoharju Emma , Marttila Saara , Mononen Nina , Lyytikäinen Leo-Pekka , Kleber Marcus E , Delgado Graciela E , Lepistö Maija , Almusa Henrikki , Ellonen Pekka , Lorkowski Stefan , März Winfried , Hutri-Kähönen Nina , Raitakari Olli , Kähönen Mika , Salonen Jukka T , Lehtimäki Terho
Published: November 2021

Mitochondria have a complex communication network with the surrounding cell and can alter nuclear DNA methylation (DNAm). Variation in the mitochondrial DNA (mtDNA) has also been linked to differential DNAm. Genome-wide association studies have identified numerous DNAm quantitative trait loci, but these studies have not examined the mitochondrial genome. Herein, we quantified nuclear DNAm from blood and conducted a mitochondrial genome-wide association study of DNAm, with an additional emphasis on sex- and prediabetes-specific heterogeneity. We used the Young Finns Study (n = 926) with sequenced mtDNA genotypes as a discovery sample and sought replication in the Ludwigshafen Risk and Cardiovascular Health study (n = 2317). We identified numerous significant associations in the discovery phase (P < 10−9), but they were not replicated when accounting for multiple testing. In total, 27 associations were nominally replicated with a P < 0.05. The replication analysis presented no evidence of sex- or prediabetes-specific heterogeneity. The 27 associations were included in a joint meta-analysis of the two cohorts, and 19 DNAm sites associated with mtDNA variants, while four other sites showed haplogroup associations. An expression quantitative trait methylation analysis was performed for the identified DNAm sites, pinpointing two statistically significant associations. This study provides evidence of a mitochondrial genetic control of nuclear DNAm with little evidence found for sex- and prediabetes-specific effects. The lack of a comparable mtDNA data set for replication is a limitation in our study and further studies are needed to validate our results.
A rare case of abdominal wall necrotizing fasciitis caused by Actinomyces europaeus—a novel pathogen
Authors: Allen Neill , James Georgina , Jain Yogesh
Published: November 2021

Actinomyces europaeus is a sub-species of actinomyces first isolated in humans in 1997. It is commensal bacteria found within the genitourinary and gastrointestinal tract. Although it is known to cause soft tissue infection and has been known to cause abscesses, it has never been identified as the primary pathogen in a case of necrotizing fasciitis. We present the case of a 59-year-old man with recurrent groin infections, poorly controlled Type 2 diabetes and obesity who developed necrotizing fasciitis of his lower abdominal wall secondary to Actinomyces europaeus. We discuss the clinical course and the value of early identification of the pathogen and specialist microbiologist advice.
A Novel Technique for Securing a Bolster For Skin Grafting after Extensive Vulvar Resection
Authors: Fei Y. Frances , Welch Kathryn C. , Haefner Hope K.
Published: November 2021

Patients with stage III hidradenitis suppurativa of the vulva and adjacent areas, unresponsive to other therapies, may require extensive surgeries. These include excision of diseased areas on the buttocks, vulva, groins, and abdomen, followed by delayed skin grafting. Negative pressure wound therapy has been used over grafts, but it can be difficult to maintain a seal when extensive areas have been resected. We present a novel technique to bolster skin grafts for optimal success. A total vulvectomy and resection of the buttocks, groins, and abdomen are first performed for stage III HS, incorporating all diseased tissue. Negative pressure wound therapy is applied and changed on postoperative day 3–4. On postoperative day 7, split-thickness skin grafts are applied. The skin grafts are covered by Adaptic gauze (3M Company, Minn.), cotton, and a layer of Reston foam (3M Company, St. Paul, Minn.) which is cut to fit the size of the wound. Ostomy skin barriers (Hollister Incorporated, Libertyville, Ill.) are placed on the skin surrounding the excised areas. Pediatric Foley catheters are then placed through the ostomy skin barriers and tied together to prevent movement of the bolster. The use of ostomy skin barriers and pediatric Foley catheters to secure bolsters has not previously been described. We demonstrate a well-tolerated technique, using common surgical supplies, to provide consistent uniform pressure over the graft site. This technique also allows for easy bedside dressing change(s) when indicated.
A Quiet Compassion
Authors: Chu Kevin
Published: November 2021

Through a difficult encounter with a new patient, the author became immersed in the messiness of patient care and learned that goals need to be defined and hard fought. The lesson learned serves as a reminder that compassion for our patients is necessary to help understand their fears and anxieties.
Characteristics of Convex Skin Barriers and Clinical Application
Authors: McNichol Laurie , Cobb Terri , Depaifve Yves , Quigley Mary , Smitka Kimberly , Gray Mikel
Published: November 2021

Regulatory bodies do not set parameters for measuring certain ostomy product characteristics. As a result, each manufacturer has a different way of measuring specific convex skin barrier characteristics that may create confusion among clinicians when selecting a product. In order to alleviate this confusion and encourage consistency in reporting product characteristics, an international meeting of clinicians with expertise in the care of persons living with an ostomy was convened. The goal of the meeting was to define and establish consistency in convex skin barrier characteristics and their clinical application of the product based on these characteristics. Twelve nurse panelists from 11 countries reviewed, discussed, and reached consensus on a group of proposed statements designed to provide standard definitions of convex skin barrier characteristics and clinically relevant application. The group reached consensus on 5 characteristics of convex skin barriers: depth, compressibility, flexibility, slope, and tension location. These statements provide a basis for quantifying the most clinically relevant characteristics of convex skin barriers and a framework for their application in clinical practice.
Psychedelic medicines for mood disorders: current evidence and clinical considerations
Authors: Sarris Jerome , Pinzon Rubiano Diego , Day Kimberley , Galvão-Coelho Nicole L. , Perkins Daniel
Published: November 2021

Purpose of review

Despite advances in treatment modalities for mood disorders over recent decades, further therapeutic options are still required. Increased research is occurring, with the pursuit of psychedelic-based pharmacotherapies for a range of mood disorders and other conditions.

Recent findings

Serotonergic psychedelics have been found to modulate brain networks underlying various psychiatric disorders, as well promoting neurogenesis and neuroplasticity. Randomized placebo-controlled trials have found psilocybin with psychological support effective at treating depression, including treatment-resistant depression; with emergent research also signalling N,N-dimethyltryptamine/ayahuasca also as a potential option for the treatment of depression. Lysergic acid diethylamide has been found to have anxiolytic effects, whereas 3,4-methylenedioxymethamphetamine (MDMA) has been used effectively to treat post-traumatic stress disorder (PTSD), with Phase III clinical trial evidence. Microdosing of psychedelics is a growing phenomenon that has shown benefits in some preclinical data; however, a recent self-directed controlled trial reported no evidence of improved mood.

Current research with medicinal psychedelics, usually as an adjunct to psychotherapy, has shown encouraging results in treating mood disorders. However, there are challenges regarding blinding and sample sizes remain small, and there have been no definitive Phase III studies (aside from MDMA for PTSD). Further work exploring novel formulations, interface with pharmacogenomics and the microbiome, and inflammatory pathways can be advised.
Massively parallel transposon mutagenesis identifies temporally essential genes for biofilm formation in Escherichia coli
Authors: Holden Emma R. , Yasir Muhammad , Turner A. Keith , Wain John , Charles Ian G. , Webber Mark A.
Published: November 2021

Biofilms complete a life cycle where cells aggregate, grow and produce a structured community before dispersing to colonize new environments. Progression through this life cycle requires temporally controlled gene expression to maximize fitness at each stage. Previous studies have largely focused on identifying genes essential for the formation of a mature biofilm; here, we present an insight into the genes involved at different stages of biofilm formation. We used TraDIS-Xpress, a massively parallel transposon mutagenesis approach using transposon-located promoters to assay the impact of disruption or altered expression of all genes in the genome on biofilm formation. We identified 48 genes that affected the fitness of cells growing in a biofilm, including genes with known roles and those not previously implicated in biofilm formation. Regulation of type 1 fimbriae and motility were important at all time points, adhesion and motility were important for the early biofilm, whereas matrix production and purine biosynthesis were only important as the biofilm matured. We found strong temporal contributions to biofilm fitness for some genes, including some where expression changed between being beneficial or detrimental depending on the stage at which they are expressed, including dksA and dsbA. Novel genes implicated in biofilm formation included zapE and truA involved in cell division, maoP in chromosome organization, and yigZ and ykgJ of unknown function. This work provides new insights into the requirements for successful biofilm formation through the biofilm life cycle and demonstrates the importance of understanding expression and fitness through time.
Interacting host modifier systems control Wolbachia-induced cytoplasmic incompatibility in a haplodiploid mite
Authors: Wybouw Nicky , Mortier Frederik , Bonte Dries
Published: November 2021

Many reproductive parasites such as Wolbachia spread within host populations by inducing cytoplasmic incompatibility (CI). CI occurs when parasite-modified sperm fertilizes uninfected eggs. In haplodiploid hosts, CI can lead to different phenotypes depending on whether the fertilized eggs die or develop into males. Genetic conflict theories predict the evolution of host modulation of CI, which in turn strongly influences the stability of reproductive parasitism. Yet, despite the ubiquity of CI-inducing parasites in nature, there is no conclusive evidence for strong intraspecific host modulation of CI strength and phenotype. Here, we tested for intraspecific host modulation of Wolbachia-induced CI in haplodiploid Tetranychus spider mites. Using a single CI-inducing Wolbachia variant and mitochondrion, a Tetranychus urticae nuclear panel was created that consisted of infected and cured near-isogenic lines. We performed a highly replicated age-synchronized full diallel cross comprised of incompatible and compatible control crosses. We uncovered host modifier systems that strongly suppress CI strength when carried by infected T. urticae males. Interspecific crosses showed that the male modifier systems suppress CI strength across species boundaries. We also observed a continuum of CI phenotypes in our crosses and identified strong intraspecific female modulation of CI phenotype when paired with a specific male genotype. Crosses established a recessive genetic basis for the maternal effect and were consistent with polygenic Mendelian inheritance. Our findings identify spermatogenesis as an important target of selection for host suppression of CI strength and underscore the importance of maternal genetic effects for the CI phenotype. Both mechanisms interacted with the genotype of the mating partner, revealing that intraspecific host modulation of CI strength and phenotype is underpinned by complex genetic architectures.
A Landmark-based Common Coordinate Framework for Spatial Transcriptomics Data
Authors: Andersson Alma , Andrusivová Žaneta , Czarnewski Paulo , Li Xiaofei , Sundström Erik , Lundeberg Joakim
Published: November 2021

1

The increasing amount of spatial transcriptomics data prompts for means to amalgamate observations from distinct experiments, especially attractive is to cast quantities from different sources into a common coordinate frame-work (CCF) to relate signals across space. We here present a method that enables transfer of information from multiple samples to a reference representing a CCF, and show its utility by analyzing an assortment of real and synthetic data sets.
networkGWAS: A network-based approach to discover genetic associations
Authors: Muzio Giulia , O’Bray Leslie , Meng-Papaxanthos Laetitia , Klatt Juliane , Borgwardt Karsten
Published: November 2021

While the search for associations between genetic markers and complex traits has led to the discovery of tens of thousands of trait-related genetic variants, the vast majority of these only explain a small fraction of observed phenotypic variation. One possible strategy to detect stronger associations is to aggregate the effects of several genetic markers and to test entire genes, pathways or (sub)networks of genes for association to a phenotype. The latter, network-based genome-wide association studies, in particular suffers from a vast search space and an inherent multiple testing problem. As a consequence, current approaches are either based on greedy feature selection, thereby risking that they miss relevant associations, or neglect doing a multiple testing correction, which can lead to an abundance of false positive findings.

To address the shortcomings of current approaches of network-based genome-wide association studies, we proposenetworkGWAS, a computationally efficient and statistically sound approach to network-based genome-wide association studies using mixed models and neighborhood aggregation. It allows for population structure correction and for well-calibratedp-values, which are obtained through circular and degree-preserving network permutation schemes.networkGWASsuccessfully detects known associations on semi-simulated common variants fromA. thalianaand on simulated rare variants fromH. sapiens, as well as neighborhoods of genes involved in stress-related biological processes on a stress-induced phenotype fromS. cerevisiae. It thereby enables the systematic combination of gene-based genome-wide association studies with biological network information.

Availability

https://github.com/BorgwardtLab/networkGWAS.git

Contact

giulia.muzio@bsse.ethz.ch,karsten.borgwardt@bsse.ethz.ch
The chromatin-regulating CoREST complex is animal specific and essential for development in the cnidarian Nematostella vectensis
Authors: Gahan James M , Hernandez-Valladares Maria , Rentzsch Fabian
Published: November 2021

Chromatin-modifying proteins are key players in the regulation of development and cell differentiation in animals. Many individual chromatin modifiers, however, predate the evolution of animal multicellularity and how they became integrated into the regulatory networks underlying development is unclear. Here we show that CoREST is an animal-specific protein that assembles a conserved, vertebrate-like histone-modifying complex including Lsd1 and HDAC1/2 in the sea anemone Nematostella vectensis. We further show that NvCoREST expression overlaps fully with that of NvLsd1 throughout development. NvCoREST mutants, generated using CRISPR-Cas9, reveal essential roles during development and for the differentiation of cnidocytes, thereby phenocopying NvLsd1 mutants. We also show that this requirement is cell autonomous using a cell-type-specific rescue approach. Together, this shows that the evolution of CoREST allowed the formation of a chromatin-modifying complex that was present before the last common cnidarian-bilaterian ancestor and thus represents an ancient component of the animal developmental toolkit.
Risky choice: probability weighting explains Independence Axiom violations in monkeys
Authors: Ferrari-Toniolo Simone , Seak Leo Chi U , Schultz Wolfram
Published: November 2021

Expected Utility Theory (EUT) provides axioms for maximizing utility in risky choice. The Independence Axiom (IA) is its most demanding axiom: preferences between two options should not change when altering both options equally by mixing them with a common gamble. We tested common consequence (CC) and common ratio (CR) violations of the IA over several months in thousands of stochastic choices using a large variety of binary option sets. Three monkeys showed consistently few outrightPreference Reversals(8%) but substantial gradedPreference Changes(46%) between the initial preferred gamble and the corresponding altered gamble. Linear Discriminant Analysis (LDA) indicated that gamble probabilities predicted mostPreference Changesin CC (72%) and CR (88%) tests. The Akaike Information Criterion indicated that probability weighting within Cumulative Prospect Theory (CPT) explained choices better than models using Expected Value (EV) or EUT. Fitting by utility and probability weighting functions of CPT resulted in nonlinear and non-parallel indifference curves (IC) in the Marschak-Machina triangle and suggested IA non-compliance of models using EV or EUT. Indeed, CPT models predictedPreference Changesbetter than EV and EUT models. Indifference points in out-of-sample tests were closer to CPT-estimated ICs than EV and EUT ICs. Finally, while the few outrightPreference Reversalsmay reflect the long experience of our monkeys, their more gradedPreference Changescorresponded to those reported for humans. In benefitting from the wide testing possibilities in monkeys, our stringent axiomatic tests contribute critical information about risky decision-making and serve as basis for investigating neuronal decision mechanisms.
Congenital Zika virus infection impairs corpus callosum development
Authors: Christoff Raissa R. , Quintanilha Jefferson H. , Ferreira Raiane O. , Ferreira Jessica C. C. G. , Guimarães Daniel M. , Valério-Gomes Bruna , Higa Luiza M. , Rossi Átila D. , Vasconcelos Janaina M. , Vianez João L.S.G. , Bellio Maria , Tanuri Amilcar , Lent Roberto , Garcez Patricia P.
Published: November 2021

Congenital Zika Syndrome (CZS) is a set of birth defects caused by Zika virus (ZIKV) infection during pregnancy. Microcephaly is its main feature, but other brain abnormalities are found in CZS patients, such as ventriculomegaly, brain calcifications, and dysgenesis of the corpus callosum. Many studies have focused on microcephaly, but it remains unknown how ZIKV infection leads to callosal malformation. To tackle this issue, we infected mouse embryosin uterowith a Brazilian ZIKV isolate and found that they are born with a reduction in callosal area and density of callosal neurons. ZIKV infection also causes a density reduction of PH3+ cells, intermediate progenitor cells and SATB2+ neurons. Moreover, axonal tracing revealed that callosal axons are reduced and misrouted. Also, ZIKV infected cultures show a reduction of callosal axon length. GFAP labelling showed thatin uteroinfection compromises glial cells responsible for midline axon guidance. The RNA-Seq data from infected brains identified downregulation of axon guidance and axonogenesis related genes. In sum, we showed that ZIKV infection impairs critical steps of corpus callosum formation by disrupting not only neurogenesis but also axon guidance and growth across the midline.

Summary Statement

Zika virus infection during development impairs the formation of corpus callosum by disturbing axon guidance and growth of callosal neurons.
MiR-144 regulates adipogenesis by mediating formation of C/EBPα-FoxO1 protein complex
Authors: Lin Weimin , Wen Xianyu , Li Xuexin , Chen Lei , Wei Wei , Zhang Lifan , Chen Jie
Published: November 2021

Excessive adipogenesis caused obesity, which was a serious risk of health and led to a series of diseases, including type II diabetes (T2D) for example. Adipocyte as the basic unit of adipose tissue has emerged as one of significant target of the treatment of obesity-related metabolic syndromes by revealed its adipogenic molecular mechanism. MicroRNAs (miRNAs) have been demonstrated involving adipogenesis, and played a crucial role in the competitive endogenous RNA (ceRNA) effect. Besides that, C/EBPα as a crucial adipogenic regulator still lacked epigenetic explanation during pre-adipocyte adipogenesis. In this study, we first verified FoxO1 was one of the ceRNA of C/EBPα. They co-regulated adipogenesis through formed a protein complex that directly bound to its promoter to activate AdipoQ, and AdipoQ (Adiponectin) was a negative adipocytokines that suppressed adipogenesis, which played an important role in retaining adipogensis balance. Moreover, an adipose tissue specific enriched miRNA, miR-144 was the key regulator of the ceRNA effect between C/EBPα and FoxO1, which mediated the C/EBPα-FoxO1 complex formation, thus altered AdipoQ, furthermore regulated pre-adipocyte adipogenesis. This research will provide a new supplementary idea of the C/EBPα epigenetic role in pre-adipocyte adipogenesis.
Structural brain connectivity predicts acute pain after mild traumatic brain injury
Authors: Branco Paulo , Bosak Noam , Bielefeld Jannis , Cong Olivia , Granovsky Yelena , Kahn Itamar , Yarnitsky David , Apkarian A. Vania
Published: November 2021

Mild traumatic brain injury, mTBI, is a leading cause of disability worldwide, with acute pain manifesting as one of its most debilitating symptoms. Understanding acute post-injury pain is important since it is a strong predictor of long-term outcomes. In this study, we imaged the brains of 172 patients with mTBI, following a motorized vehicle collision and used a machine learning approach to extract white matter structural and resting state fMRI functional connectivity measures to predict acute pain. Stronger white matter tracts within the sensorimotor, thalamic-cortical, and default-mode systems predicted 20% of the variance in pain severity within 72 hours of the injury. This result generalized in two independent groups: 39 mTBI patients and 13 mTBI patients without whiplash symptoms. White matter measures collected at 6-months after the collision still predicted mTBI pain at that timepoint (n = 36). These white-matter connections were associated with two nociceptive psychophysical outcomes tested at a remote body site – namely conditioned pain modulation and magnitude of suprathreshold pain–, and with pain sensitivity questionnaire scores. Our validated findings demonstrate a stable white-matter network, the properties of which determine a significant amount of pain experienced after acute injury, pinpointing a circuitry engaged in the transformation and amplification of nociceptive inputs to pain perception.
Pangenome evolution in environmentally transmitted symbionts of deep-sea mussels is governed by vertical inheritance
Authors: Picazo Devani Romero , Werner Almut , Dagan Tal , Kupczok Anne
Published: November 2021

Microbial pangenomes vary across species; their size and structure are determined by genetic diversity within the population and by gene loss and horizontal gene transfer (HGT). Many bacteria are associated with eukaryotic hosts where the host colonization dynamics may impact bacterial genome evolution. Host-associated lifestyle has been recognized as a barrier to HGT in parentally transmitted bacteria. However, pangenome evolution of environmentally acquired symbionts remains understudied, often due to limitations in symbiont cultivation. Using high-resolution metagenomics, here we study pangenome evolution of two co-occurring endosymbionts inhabiting Bathymodiolus brooksi mussels from a single cold seep. The symbionts, sulfur-oxidizing (SOX) and methane-oxidizing (MOX) gamma-proteobacteria, are environmentally acquired at an early developmental stage and individual mussels may harbor multiple strains of each species. We found differences in the accessory gene content of both symbionts across individual mussels, which are reflected by differences in symbiont strain composition. Compared to core genes, accessory genes are enriched in functions involved in genome integrity. We found no evidence for recent horizontal gene transfer between both symbionts. A comparison between the symbiont pangenomes revealed that the MOX population is less diverged and contains fewer accessory genes, supporting that the MOX association with B. brooksi is more recent than that of SOX. Our results show that the pangenomes of both symbionts evolved mainly by vertical inheritance. We conclude that environmentally transmitted symbionts that associate with individual hosts over their lifetime show features of narrow symbioses, where the frequency of HGT is constrained.
Microglial phagocytosis dysfunction during stroke is prevented by rapamycin
Authors: Beccari S , Sierra-Torre V , Valero J , García-Zaballa M , Carretero-Guillen A , Capetillo-Zarate E , Domercq M , Huguet PR , Ramonet D , Osman A , Han W , Dominguez C , Faust TE , Touzani O , Boya P , Schafer D , Mariño G , Canet-Soulas E , Blomgren K , Plaza-Zabala A , Sierra A
Published: November 2021

Microglial phagocytosis is rapidly emerging as a therapeutic target in neurodegenerative and neurological disorders. An efficient removal of cellular debris is necessary to prevent buildup damage of neighbor neurons and the development of an inflammatory response. As the brain professional phagocytes, microglia are equipped with an array of mechanisms that enable them to recognize and degrade several types of cargo, including neurons undergoing apoptotic cell death. While microglia are very competent phagocytes of apoptotic cells under physiological conditions, here we report their dysfunction in mouse and monkey (Macaca fascicularisandCallithrix jacchus) models of stroke by transient occlusion of the medial cerebral artery (tMCAo). The impairment of both engulfment and degradation was related to energy depletion triggered by oxygen and nutrients deprivation (OND), which led to reduced process motility, lysosomal depletion, and the induction of a protective autophagy response in microglia. Basal autophagy, which is in charge of removing and recycling intracellular elements, was critical to maintain microglial physiology, including survival and phagocytosis, as we determined both in vivo and in vitro using knock-out models of autophagy genes and the autophagy inhibitor MRT68921. Notably, the autophagy inducer rapamycin partially prevented the phagocytosis impairment induced by tMCAo in vivo but not by OND in vitro. These results suggest a more complex role of microglia in stroke than previously acknowledged, classically related to the inflammatory response. In contrast, here we demonstrate the impairment of apoptotic cell phagocytosis, a microglial function critical for brain recovery. We propose that phagocytosis is a therapeutic target yet to be explored and provide evidence that it can be modulated in vivo using rapamycin, setting the stage for future therapies for stroke patients.