bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of echocardiographic and cardiac magnetic resonance imaging abnormalities during follow-up in patients with multisystem inflammatory syndrome in children
Authors: Sirico D , Basso A , Sabatino J , Reffo E , Cavaliere A , Biffanti R , Cerutti A , Castaldi B , Zulian F , Da Dalt L , Di Salvo G
Published: May 2022

Aims

Multisystem inflammatory syndrome in children (MIS-C) with cardiovascular manifestations are frequent. However, there is lacking evidence regarding cardiological follow-up of this cohort of patients. The aim of our study was to describe the early and mid-term cardiac abnormalities assessed by standard and speckle-tracking echocardiography (STE), and cardiac MRI (CMR).

Methods and results

We enrolled 32 patients (21 male, 11 female), mean age 8.25 ± 4years, with diagnosis of MIS-C. During admission, all children underwent TTE, STE with analysis of left ventricle global longitudinal strain (GLS) and CMR. Patients underwent cardiological evaluation at 2 (T1) and 6 months (T2) after discharge. Cardiac MRI was repeated at 6 months after discharge. Mean left ventricular ejection fraction (LVEF) at baseline was 58.8 ± 10% with 10 patients (31%) below 55%. Speckle-tracking echocardiography showed reduced mean LV GLS (−17.4 ± 4%). On CMR, late gadolinium enhancement (LGE) with non-ischaemic pattern was evident in 8 of 23 patients (35%). Follow-up data showed rapid improvement of LVEF at T1 (62.5 ± 7.5 vs. 58.8 ± 10.6%, P-value 0.044) with only three patients (10%) below ≤ 55% at T1. Left ventricular (LV) GLS remained impaired at T1 (−17.2 ± 2.7 vs.−17.4 ± 4, P-value 0.71) and significantly improved at T2 (−19 ± 2.6% vs. −17.4 ± 4%, P-value 0.009). LV GLS was impaired (>−18%) in 53% of patients at baseline and T1, whereas only 13% showed persistent LV GLS reduction at T2. Follow-up CMR showed LGE persistence in 33.4% of cases.

Conclusion

Early cardiac involvement significantly improves during follow-up of MIS-C patients. However, subclinical myocardial dysfunction seems to be still detectable after 6 months of follow-up in a not negligible proportion of them.
Molecular approaches improving our understanding ofBrettanomycesphysiology
Authors: Varela Cristian , Borneman Anthony R
Published: May 2022

Brettanomyces species, and particularly B. bruxellensis as the most studied representative, are strongly linked to industrial fermentation processes. This association is considered either positive or undesirable depending on the industry. While in some brewing applications and in kombucha production Brettanomyces yeasts contribute to the flavour and aroma profile of these beverages, in winemaking and bioethanol production Brettanomyces is considered a spoilage or contaminant microorganism. Nevertheless, understanding Brettanomyces biology and metabolism in detail will benefit all industries. This review discusses recent molecular biology tools including genomics, transcriptomics, and genetic engineering techniques that can improve our understanding of Brettanomyces physiology and how these approaches can be used to make the industrial potential of this species a reality.
Highly efficient site-specific integration of DNA fragments into the honeybee genome using CRISPR/Cas9
Authors: Wagner Anna , Seiler Jana , Beye Martin
Published: May 2022

Functional genetic studies in honeybees have been limited to transposon mediated transformation and site directed mutagenesis tools. However, site- and sequence-specific manipulations that insert DNA fragments or replace sequences at specific target sites are lacking. Such tools would enable the tagging of proteins, the expression of reporters and site-specific amino acid changes, which are all gold standard manipulations for physiological, organismal, and genetic studies. However, such manipulations must be very efficient in honeybees since screening and crossing procedures are laborious due to their social organization. Here, we report an accurate and remarkably efficient site-specific integration of DNA-sequences into the honeybee genome using clustered regularly interspaced short palindromic repeat/clustered regularly interspaced short palindromic repeat-associated protein 9-mediated homology-directed repair. We employed early embryonic injections and selected a highly efficient sgRNA in order to insert 294 and 729 bp long DNA sequences into a specific locus at the dsx gene. These sequences were locus-specifically integrated in 57% and 59% of injected bees. Most importantly, 21% and 25% of the individuals lacked the wildtype sequence demonstrating that we generated homozygous mutants in which all cells are affected (no mosaicism). The highly efficient, locus-specific insertions of nucleotide sequences generating homozygous mutants demonstrate that systematic molecular studies for honeybees are in hand that allow somatic mutation approaches via workers or studies in the next generation using queens with their worker progeny. The employment of early embryonic injections and screenings of highly efficient sgRNAs may offer the prospect of highly successful sequence- and locus-specific mutations also in other organisms.
The Drosophila melanogaster enzyme glycerol-3-phosphate dehydrogenase 1 is required for oogenesis, embryonic development, and amino acid homeostasis
Authors: Rai Madhulika , Carter Sarah M , Shefali Shefali A , Mahmoudzadeh Nader H , Pepin Robert , Tennessen Jason M
Published: May 2022

As the fruit fly, Drosophila melanogaster, progresses from one life stage to the next, many of the enzymes that compose intermediary metabolism undergo substantial changes in both expression and activity. These predictable shifts in metabolic flux allow the fly meet stage-specific requirements for energy production and biosynthesis. In this regard, the enzyme glycerol-3-phosphate dehydrogenase 1 (GPDH1) has been the focus of biochemical genetics studies for several decades and, as a result, is one of the most well-characterized Drosophila enzymes. Among the findings of these earlier studies is that GPDH1 acts throughout the fly lifecycle to promote mitochondrial energy production and triglyceride accumulation while also serving a key role in maintaining redox balance. Here, we expand upon the known roles of GPDH1 during fly development by examining how depletion of both the maternal and zygotic pools of this enzyme influences development, metabolism, and viability. Our findings not only confirm previous observations that Gpdh1 mutants exhibit defects in larval development, lifespan, and fat storage but also reveal that GPDH1 serves essential roles in oogenesis and embryogenesis. Moreover, metabolomics analysis reveals that a Gpdh1 mutant stock maintained in a homozygous state exhibits larval metabolic defects that significantly differ from those observed in the F1 mutant generation. Overall, our findings highlight unappreciated roles for GPDH1 in early development and uncover previously undescribed metabolic adaptations that could allow flies to survive the loss of this key enzyme.
Population Genetics of Reproductive Genes in Haplodiploid Species
Authors: Dapper Amy L. , Slater Garett P. , Shores Katherynne , Harpur Brock A.
Published: May 2022

Many animal species are haplodiploid: their fertilized eggs develop into diploid females and their unfertilized eggs develop into haploid males. The unique genetic features of haplodiploidy raise the prospect that these systems can be used to disentangle the population genetic consequences of haploid and diploid selection. To this end, sex-specific reproductive genes are of particular interest because, while they are shared within the same genome, they consistently experience selection in different ploidal environments. However, other features of these genes, including sex-specific expression and putative involvement in postcopulatory sexual selection, are potentially confounding factors because they may also impact the efficacy of selection asymmetrically between the sexes. Thus, to properly interpret evolutionary genomic patterns, it is necessary to generate a null expectation for the relative amount of polymorphism and divergence we expect to observe among sex-specific genes in haplodiploid species, given differences in ploidal environment, sex-limited expression, and their potential role in sexual selection. Here, we derive the theoretical expectation for the rate of evolution of sex-specific genes in haplodiploid species, under the assumption that they experience the same selective environment as genes expressed in both sexes. We find that the null expectation is that reproductive genes evolve more rapidly than constitutively expressed genes in haplodiploid genomes. However, despite the aforementioned differences, the null expectation does not differ between male- and female-specific reproductive genes, when assuming additivity. Our theoretical results provide an important baseline expectation that should be used in molecular evolution studies comparing rates of evolution among classes of genes in haplodiploid species.
BioKIT: a versatile toolkit for processing and analyzing diverse types of sequence data
Authors: Steenwyk Jacob L , Buida Thomas J , Gonçalves Carla , Goltz Dayna C , Morales Grace , Mead Matthew E , LaBella Abigail L , Chavez Christina M , Schmitz Jonathan E , Hadjifrangiskou Maria , Li Yuanning , Rokas Antonis
Published: May 2022

Bioinformatic analysis—such as genome assembly quality assessment, alignment summary statistics, relative synonymous codon usage, file format conversion, and processing and analysis—is integrated into diverse disciplines in the biological sciences. Several command-line pieces of software have been developed to conduct some of these individual analyses, but unified toolkits that conduct all these analyses are lacking. To address this gap, we introduce BioKIT, a versatile command line toolkit that has, upon publication, 42 functions, several of which were community-sourced, that conduct routine and novel processing and analysis of genome assemblies, multiple sequence alignments, coding sequences, sequencing data, and more. To demonstrate the utility of BioKIT, we conducted a comprehensive examination of relative synonymous codon usage across 171 fungal genomes that use alternative genetic codes, showed that the novel metric of gene-wise relative synonymous codon usage can accurately estimate gene-wise codon optimization, evaluated the quality and characteristics of 901 eukaryotic genome assemblies, and calculated alignment summary statistics for 10 phylogenomic data matrices. BioKIT will be helpful in facilitating and streamlining sequence analysis workflows. BioKIT is freely available under the MIT license from GitHub (https://github.com/JLSteenwyk/BioKIT), PyPi (https://pypi.org/project/jlsteenwyk-biokit/), and the Anaconda Cloud (https://anaconda.org/jlsteenwyk/jlsteenwyk-biokit). Documentation, user tutorials, and instructions for requesting new features are available online (https://jlsteenwyk.com/BioKIT).
Tobacco advertisement, promotion and sponsorship in Arabic media between 2017 and 2019
Authors: Monshi Sarah S , Collins Bradley N , Wu Jingwei , Alzahrani Mona Ahmed J , Ibrahim Jennifer K
Published: May 2022

Nineteen out of 22 countries in the Eastern Mediterranean region, including the Gulf Cooperation Council countries, have ratified the World Health Organization Framework Convention on Tobacco Control (FCTC) treaty. One of FCTC’s provisions prohibits tobacco advertisement, promotion and sponsorship (TAPS). The TAPS provision requires nations to ban direct and indirect tobacco ads in media, as exposure to tobacco use in the media encourages smoking initiation. A limited number of studies have examined TAPS in Arabic media. This study examined the occurrence of tobacco use across Arabic television (TV) series released between January 2017 and December 2019 to assess compliance with the FCTC provision banning TAPS. The content analysis examined incidents of tobacco use in Arabic TV series, types of tobacco products used and the portrayal of second-hand smoking exposure. Out of 92 Arabic TV series (2952 episodes), there were 32 044 incidents of tobacco use. Incidents of tobacco use per episode fluctuated over time. During Ramadan, the median number of tobacco incidents declined from 6 in 2017 to 3 in 2019; however, it increased to 8 in 2018. Regular cigarettes and water pipes were the most common tobacco products used in TV series. While 27% of tobacco use showed characters who smoked tobacco products alone, 13% of the incidents portrayed characters who were smoking in the presence of children. This study concludes that tobacco imagery is not completely banned in Arabic media and its continued representation weakens tobacco control measures.
Understanding the child mortality decline in Guinea-Bissau: the role of population-level nutritional status measured by mid-upper arm circumference
Authors: Rieckmann Andreas , Fisker Ane Bærent , Øland Christian Bjerregård , Nielsen Sebastian , Wibaek Rasmus , Sørensen Tina Bonde , Martins Cesário Lourenço , Benn Christine Stabell , Aaby Peter
Published: May 2022

Background

Malnutrition is considered an important contributing factor to child mortality, and the mid-upper arm circumference (MUAC) is regarded as one of the better anthropometric predictors of child mortality. We explored whether the decline in child mortality over recent decades could be explained by changes in children’s MUAC.

Methods

This prospective study analysed individual-level data from 47 731 children from the capital of Guinea-Bissau followed from 3 months until 36 months of age over 2003 to 2016. We used standardization to compare the mortality rate as if only the MUAC distribution had changed between an early period (2003–05) and a late period (2014–16). We adjusted the analyses for age, sex, socioeconomic-related possessions and maternal education.

Results

A total of 949 deaths were included in the analysis. The adjusted mortality rate was 18.9 [95% confidence interval (CI) 14.3-23.3] deaths per 1000 person-years (pyrs) in the early period and declined to 4.4 (95% CI 2.9-6.0) deaths per 1000 pyrs in the late period, a 77% (95% CI 71-83%) reduction in the mortality rate. At all calendar years, the MUAC distribution in the population was close to the WHO reference population. MUAC below -1 z-score was associated with increased child mortality. The change in MUAC distribution from the early period to the late period (in the early period mortality standardization) corresponded to 1.5 (95% CI 1.0-2.2) fewer deaths per 1000 pyrs, equivalent to 11% (95% CI 7-14%) of the observed change in child mortality.

Conclusions

From 2003 to 2016, child mortality in urban Guinea-Bissau declined considerably but, though a low MUAC was associated with increased mortality, changes in the MUAC distribution in the population explained little of the decline. Understanding the driving factors of child mortality decline can help scope tomorrow’s interventions.
Formative service evaluation of transfer of care service for care home residents after hospital discharge
Authors: Kandiah Janani , Nazar Hamde , Wright David
Published: May 2022

Objectives

This study provides a service description and analysis of a pilot across two sites involving pharmacists aiming to support care home residents with their medications post-discharge.

Methods

An interview with the pilot coordinator was undertaken to understand the pilot service. Service data (March 2020–June 2021) were analysed to investigate what was actually delivered to the care home residents.

Key findings

One hundred eighty-eight inpatients were referred and 132 received the post-discharge service. One hundred three residents received medicines reconciliation and 29 received an additional structured medication review. The latter cohort was significantly more likely to receive medicines and illness-related information and have medicines stopped.

Conclusions

The service facilitates the provision of medicines information and medicines-related interventions. Further evaluation is required to evidence the value of medicines review alongside the medicines reconciliation.
Influence of daptomycin doses on the outcomes of VRE bloodstream infection treated with high-dose daptomycin
Authors: Chuang Yu Chung , Lin Hsin Yi , Yang Jia Ling , Lin Chi Ying , Huang Sung Hsi , Wang Jann Tay , Chen Yee Chun , Chang Shan Chwen
Published: May 2022

Objectives

The CLSI recommended high-dose daptomycin (8–12 mg/kg) for treating Enterococcus faecium bloodstream infections (BSI). The current study was designed to determine the safety and efficacy of increasing the daptomycin dose for VRE BSI patients receiving ≥8 mg/kg.

Methods

We conducted a multicentre prospective observational study of patients who received a ≥8 mg/kg dose of daptomycin for treatment of VRE BSI. The primary outcome was 28 day mortality.

Results

A total of 661 patients were included. The 28 day mortality rate was 45.1%. The survivors received higher doses of daptomycin than non-survivors (10.1 versus 9.8 mg/kg; P < 0.001). An increase in the daptomycin dose independently predicted lower mortality [adjusted OR (aOR) = 0.85; 95% CI = 0.73–0.99; P = 0.03]. Eighty-six survivors (23.7%) and 43 non-survivors (14.4%) received a ≥11 mg/kg dose of daptomycin (P = 0.003). The 8 to <11 and ≥11 mg/kg doses of daptomycin differed in the 28 day mortality in the higher MIC group (≥2 mg/L) (49.4% versus 33.3%; P = 0.004), but not in the lower MIC group (≤1 mg/L) (29.3% versus 29.4%; P = 0.99). A dose of ≥11 mg/kg was associated with a higher (3.9%) rate of highly elevated creatine kinase (>2000 U/L) compared with 1.1% with 8 to <11 mg/kg (P = 0.04).

Conclusions

The efficacy of daptomycin is dose dependent. A high daptomycin dose, especially at ≥11 mg/kg, improved survival in patients with VRE BSI, but was associated with highly elevated creatine kinase. We recommend a ≥11 mg/kg dose of daptomycin be considered for treatment of VRE BSI, particularly for isolates with higher MICs.
dPQL: a lossless distributed algorithm for generalized linear mixed model with application to privacy-preserving hospital profiling
Authors: Luo Chongliang , Islam Md Nazmul , Sheils Natalie E , Buresh John , Schuemie Martijn J , Doshi Jalpa A , Werner Rachel M , Asch David A , Chen Yong
Published: May 2022

Objective

To develop a lossless distributed algorithm for generalized linear mixed model (GLMM) with application to privacy-preserving hospital profiling.

Materials and Methods

The GLMM is often fitted to implement hospital profiling, using clinical or administrative claims data. Due to individual patient data (IPD) privacy regulations and the computational complexity of GLMM, a distributed algorithm for hospital profiling is needed. We develop a novel distributed penalized quasi-likelihood (dPQL) algorithm to fit GLMM when only aggregated data, rather than IPD, can be shared across hospitals. We also show that the standardized mortality rates, which are often reported as the results of hospital profiling, can also be calculated distributively without sharing IPD. We demonstrate the applicability of the proposed dPQL algorithm by ranking 929 hospitals for coronavirus disease 2019 (COVID-19) mortality or referral to hospice that have been previously studied.

Results

The proposed dPQL algorithm is mathematically proven to be lossless, that is, it obtains identical results as if IPD were pooled from all hospitals. In the example of hospital profiling regarding COVID-19 mortality, the dPQL algorithm reached convergence with only 5 iterations, and the estimation of fixed effects, random effects, and mortality rates were identical to that of the PQL from pooled data.

Conclusion

The dPQL algorithm is lossless, privacy-preserving and fast-converging for fitting GLMM. It provides an extremely suitable and convenient distributed approach for hospital profiling.
Characterization and utilization of methyltransferase for apramycin production in Streptoalloteichus tenebrarius
Authors: Sun Junyang , Gao Hongjing , Yan Danyang , Liu Yu , Ni Xianpu , Xia Huanzhang
Published: May 2022

A structurally unique aminoglycoside produced in Streptoalloteichus tenebrarius, Apramycin is used in veterinary medicine or the treatment of Salmonella, Escherichia coli, and Pasteurella multocida infections. Although apramycin was discovered nearly 50 years ago, many biosynthetic steps of apramycin remain unknown. In this study, we identified a HemK family methyltransferase, AprI, to be the 7’-N-methyltransferase in apramycin biosynthetic pathway. Biochemical experiments showed that AprI converted demethyl-aprosamine to aprosamine. Through gene disruption of aprI, we identified a new aminoglycoside antibiotic demethyl-apramycin as the main product in aprI disruption strain. The demethyl-apramycin is an impurity in apramycin product. In addition to demethyl-apramycin, carbamyltobramycin is another major impurity. However, unlike demethyl-apramycin, tobramycin is biosynthesized by an independent biosynthetic pathway in S. tenebrarius. The titer and rate of apramycin were improved by overexpression of the aprI and disruption of the tobM2, which is a crucial gene for tobramycin biosynthesis. The titer of apramycin increased from 2227 ± 320 mg/L to 2331 ± 210 mg/L, while the titer of product impurity demethyl-apramycin decreased from 196 ± 36 mg/L to 51 ± 9 mg/L. Moreover, the carbamyltobramycin titer of the wild-type strain was 607 ± 111 mg/L and that of the engineering strain was null. The rate of apramycin increased from 68% to 87% and that of demethyl-apramycin decreased from 1.17% to 0.34%.
Bioethics and the Contours of Autonomy
Authors: Estes Derek
Published: May 2022

The principle of respect for autonomy often dominates the bioethical discourse. Yet despite its prominence, the exact contours are not always well defined. Widespread disagreement about the nature of autonomy has led some to conclude that autonomy is hopelessly vague and therefore ought to be abandoned in contemporary bioethics. Despite calls to move beyond it, autonomy remains at the center of bioethical reflection. The challenge, then, if autonomy is to function as a bedrock of contemporary bioethics, is to define more clearly the shape of autonomy, to mark more precisely its conceptual boundaries, and to delineate more carefully how best autonomy is put into practice in medical ethics. In this article, I raise questions about the ways autonomy is used in theory, as well as the ways that it is operationalized in practice.
Rare giant female adnexal tumor of probable Wolffian origin: a case report
Authors: Brzika Sanela , Rašić Ismar , Bektešević Admir , Gavrankapetanović Ali , Hasić Nedim , Pašović Salko
Published: May 2022

Female adnexal tumors of probable Wolffian origin (FATWOs) are extremely rare tumors, with only around 100 cases published worldwide. FATWOs are most frequently found in the broad ligament, but these can also appear in the mesosalpinx, Fallopian tube, ovary, paravaginal region or peritoneum. We present a case of a 68-year-old female with a history of painless abdominal distension and frequent urination, with palpable big abdominal mass. Initial diagnosis was made using ultrasound and computed tomography scan that showed 22 × 21-cm tumor with solid and cystic components. Blood test showed elevated serum levels of CA 125, HE4 and Roma index. Intraoperatively, a large abdominopelvic encapsulated mass, fixated to surrounding tissue, was found. Our patient underwent hysterectomy 12 years ago. Total tumor resection, including bilateral adnexectomy, was performed. At 6 months of following, there was no evidence of disease. Here, we report extremely rare abdominal tumors and one of the biggest FATWOs reported so far.
Jasmonate Hypersensitive 3 negatively regulates both jasmonate and ethylene-mediated responses in Arabidopsis
Authors: Chung KwiMi , Demianski Agnes J , Harrison Gregory A , Laurie-Berry Neva , Mitsuda Nobutaka , Kunkel Barbara N
Published: May 2022

Jasmonate (JA) is an important hormone involved in regulating diverse responses to environmental factors as well as growth and development, and its signalling is influenced by other hormones such as ethylene (ET). However, our understanding of the regulatory relationship between the JA and ET signalling pathways is limited. In this study, we isolated an Arabidopsis JA-hypersensitive mutant, jah3 (jasmonate hypersensitive3)-1. Map-based cloning revealed that the JAH3 gene corresponds to At4g16535. JAH3 encodes a protein of unknown function whose amino acid sequence has similarity to leukocyte receptor cluster-like protein. The mutation in jah3-1 is caused by a single nucleotide change from A to T at position 220 of 759 bp. Using CRISPR-Cas9, we generated a second allele, jah3-2, that encodes a truncated protein. Both of these loss-of-function alleles resulted in hypersensitivity to JA, ET-induced root growth inhibition, and accelerated dark-induced senescence. Double mutant analyses employing coronatine insensitive 1 (coi1) and ethylene insensitive 3 (ein3) mutants (jah3 coi1 and jah3 ein3) demonstrated that the hypersensitive phenotypes of the jah3 mutants are mediated by JA and ET signalling components COI1 and EIN3. Therefore, we propose that JAH3 is a negative regulator of both JA and ET signalling.
Other Looks: Chicana/o Responses to US Magazine Aesthetics
Authors: Merport Quiñones Carmen
Published: May 2022

I argue that Chicana/o artists and activists working in the second half of the twentieth century engaged with the visual culture of US mass picture magazines such as Life because they identified it as a crucial site of struggle even as they recognized the increasing significance of other mass media. Examining pages from Life throughout the years, I show how Henry Luce’s magazine used derogatory depictions of racialized subjects to sell a particular notion of readerly belonging to a white middle-class audience. I find traces of distinct activist and artistic responses to this biased visual culture in the pages of Chicano Movement periodicals such as La Raza, in a Time spread on author Carlos Castaneda, and in the collaboration of two Chicano avant-gardists, Teddy Sandoval and Gronk. Each of these practices, I argue, provide different perspectives on the degree to which the social imaginary and protocols of the magazine medium availed the formation of minoritarian counter-discourses. While the mass picture magazine has faded from prominence, becoming a mere shadow of what it once was, the visual culture that emerged from its glossy pages still haunts our present. As a result, the activist and artistic interventions discussed in this essay provide us with important models for rethinking contemporary efforts to transform the racial logics of the mass cultural sphere.
Modelling star cluster formation: Mergers
Authors: Karam Jeremy , Sills Alison
Published: May 2022

Star cluster formation in giant molecular clouds involves the local collapse of the cloud into small gas-rich subclusters, which can then subsequently collide and merge to build up the final star cluster(s). In this paper, we simulate collisions between these subclusters, using coupled smooth particle hydrodynamics for the gas and N-body dynamics for the stars. We are guided by previous radiation hydrodynamics simulations of molecular cloud collapse which provide the global properties of the colliding clusters, such as their stellar and gas masses, and their initial positions and velocities. The subclusters in the original simulation were treated as sink particles which immediately merged into a single entity after the collision. We show that the more detailed treatment provides a more complex picture. At collisional velocities above ≈ 10 km/s, the stellar components of the cluster do not form a monolithic cluster within 3 Myr, although the gas may do so. At lower velocities, the clusters do eventually merge but over timescales that may be longer than the time for a subsequent collision. The structure of the resultant cluster is not well-fit by any standard density distribution, and the clusters are not in equilibrium but continue to expand over our simulation time. We conclude that the simple sink particle treatment of subcluster mergers in large-scale giant molecular cloud simulations provides an upper limit on the final cluster properties.
Screening mechanism and late-time cosmology: Role of a Chameleon–Brans–Dicke scalar field
Authors: Chakrabarti Soumya , Dutta Koushik , Said Jackson Levi
Published: May 2022

We discuss a way in which the geometric scalar field in a Brans–Dicke (BD) theory can evade local astronomical tests and act as a driver of the late-time cosmic acceleration. This requires a self-interaction of the BD scalar as well as an interaction with ordinary matter. The scalar field in this construct acquires a density-dependent effective mass much like a Chameleon field. We discuss the viability of this setup in the context of Equivalence Principle, Fifth Force, and Solar System tests. The cosmological consistency is adjudged in comparison with observational data from recalibrated light curves of type Ia supernova (JLA), the Hubble parameter measurements (OHD) and the Baryon Acoustic Oscillation (BAO). We deduct that the astrophysical constraints indeed favour the existence of a mild scalar-matter interaction in the Jordan Frame.
The evolution of turbulent galactic discs: gravitational instability, feedback, and accretion
Authors: Ginzburg Omri , Dekel Avishal , Mandelker Nir , Krumholz Mark R
Published: May 2022

We study the driving of turbulence in star-forming disc galaxies of different masses at different epochs, using an analytic ‘bathtub’ model. The disc of gas and stars is assumed to be in marginal Toomre instability. Turbulence is assumed to be sustained via an energy balance between its dissipation and three simultaneous energy sources. These are stellar feedback, inward transport due to disc instability and clumpy accretion via streams. The transport rate is computed with two different formalisms, with similar results. To achieve the energy balance, the disc self-regulates either the mass fraction in clumps or the turbulent viscous torque parameter. In this version of the model, the efficiency by which the stream kinetic energy is converted into turbulence is a free parameter, ξa. We find that the contributions of the three energy sources are in the same ball park, within a factor of ∼2 in all discs at all times. In haloes that evolve to a mass $\le 10^{12}\, {\rm M_{\odot }}$ by z = 0 ($\le 10^{11.5}\, {\rm M_{\odot }}$ at z ∼ 2), feedback is the main driver throughout their lifetimes. Above this mass, the main driver is either transport or accretion for very low or very high values of ξa, respectively. For an assumed ξa(t) that declines in time, galaxies in haloes with present-day mass >1012 M⊙ make a transition from accretion to transport dominance at intermediate redshifts, z ∼ 3, when their mass was ${\ge }10^{11.5}\, {\rm M_{\odot }}$. The predicted relation between star formation rate and gas velocity dispersion is consistent with observations.
Synthesis of RNA-cofactor conjugates and structural exploration of RNA recognition by an m6A RNA methyltransferase
Authors: Meynier Vincent , Iannazzo Laura , Catala Marjorie , Oerum Stephanie , Braud Emmanuelle , Atdjian Colette , Barraud Pierre , Fonvielle Matthieu , Tisné Carine , Ethève-Quelquejeu Mélanie
Published: May 2022

Chemical synthesis of RNA conjugates has opened new strategies to study enzymatic mechanisms in RNA biology. To gain insights into poorly understood RNA nucleotide methylation processes, we developed a new method to synthesize RNA-conjugates for the study of RNA recognition and methyl-transfer mechanisms of SAM-dependent m6A RNA methyltransferases. These RNA conjugates contain a SAM cofactor analogue connected at the N6-atom of an adenosine within dinucleotides, a trinucleotide or a 13mer RNA. Our chemical route is chemo- and regio-selective and allows flexible modification of the RNA length and sequence. These compounds were used in crystallization assays with RlmJ, a bacterial m6A rRNA methyltransferase. Two crystal structures of RlmJ in complex with RNA–SAM conjugates were solved and revealed the RNA-specific recognition elements used by RlmJ to clamp the RNA substrate in its active site. From these structures, a model of a trinucleotide bound in the RlmJ active site could be built and validated by methyltransferase assays on RlmJ mutants. The methyl transfer by RlmJ could also be deduced. This study therefore shows that RNA-cofactor conjugates are potent molecular tools to explore the active site of RNA modification enzymes.
Ccr4–Not complex reduces transcription efficiency in heterochromatin
Authors: Monteagudo-Mesas Pablo , Brönner Cornelia , Kohvaei Parastou , Amedi Haris , Canzar Stefan , Halic Mario
Published: May 2022

Heterochromatic silencing is thought to occur through a combination of transcriptional silencing and RNA degradation, but the relative contribution of each pathway is not known. In this study, we analyzed RNA Polymerase II (RNA Pol II) occupancy and levels of nascent and steady-state RNA in different mutants of Schizosaccharomyces pombe, in order to quantify the contribution of each pathway to heterochromatic silencing. We found that transcriptional silencing consists of two components, reduced RNA Pol II accessibility and, unexpectedly, reduced transcriptional efficiency. Heterochromatic loci showed lower transcriptional output compared to euchromatic loci, even when comparable amounts of RNA Pol II were present in both types of regions. We determined that the Ccr4–Not complex and H3K9 methylation are required for reduced transcriptional efficiency in heterochromatin and that a subset of heterochromatic RNA is degraded more rapidly than euchromatic RNA. Finally, we quantified the contribution of different chromatin modifiers, RNAi and RNA degradation to each silencing pathway. Our data show that several pathways contribute to heterochromatic silencing in a locus-specific manner and reveal transcriptional efficiency as a new mechanism of silencing.
Diagnostic potential of extracellular vesicles in meningioma patients
Authors: Ricklefs Franz L , Maire Cecile L , Wollmann Kathrin , Dührsen Lasse , Fita Krystian D , Sahm Felix , Herold-Mende Christel , von Deimling Andreas , Kolbe Katharina , Holz Mareike , Bergmann Leonie , Fuh Marceline M , Schlüter Hartmut , Alawi Malik , Reimer Rudolph , Peine Sven , Glatzel Markus , Westphal Manfred , Lamszus Katrin
Published: May 2022

Background

Extracellular vesicles (EVs) play an important role in cell–cell communication, and tumor-derived EVs circulating in patient blood can serve as biomarkers. Here, we investigated the potential role of plasma EVs in meningioma patients for tumor detection and determined whether EVs secreted by meningioma cells reflect epigenetic, genomic, and proteomic alterations of original tumors.

Methods

EV concentrations were quantified in patient plasma (n = 46). Short-term meningioma cultures were established (n = 26) and secreted EVs were isolated. Methylation and copy number profiling was performed using 850k arrays, and mutations were identified by targeted gene panel sequencing. Differential quantitative mass spectrometry was employed for proteomic analysis.

Results

Levels of circulating EVs were elevated in meningioma patients compared to healthy individuals, and the plasma EV concentration correlated with malignancy grade and extent of peritumoral edema. Postoperatively, EV counts dropped to normal levels, and the magnitude of the postoperative decrease was associated with extent of tumor resection. Methylation profiling of EV-DNA allowed correct tumor classification as meningioma in all investigated cases, and accurate methylation subclass assignment in almost all cases. Copy number variations present in tumors, as well as tumor-specific mutations were faithfully reflected in meningioma EV-DNA. Proteomic EV profiling did not permit original tumor identification but revealed tumor-associated proteins that could potentially be utilized to enrich meningioma EVs from biofluids.

Conclusions

Elevated EV levels in meningioma patient plasma could aid in tumor diagnosis and assessment of treatment response. Meningioma EV-DNA mirrors genetic and epigenetic tumor alterations and facilitates molecular tumor classification.
Identification of UHT Granulites in the Pan-African Dahomeyide Suture Zone in SE Ghana: Implications for Evolution of Collisional Orogens
Authors: Aidoo Felix , Zhang Qiang-Qiang , Zhang Shao-Bing , Nude Prosper M
Published: May 2022

This study presents the petrology, geochemistry, U–Pb ages, Lu–Hf and oxygen isotope compositions of Adaklu mafic granulites (ADMGs), from the Pan-African Dahomeyide suture zone in southeastern Ghana. The ADMGs show mafic precursor with low-K tholeiitic affinity. They display convex rare earth and trace elements characteristics without any obvious anomalies of Eu, Ti, Nb and Ta. The geochemical characteristics of ADMGs mimic those of N-MORB. Zircon U–Pb dating on the ADMGs reveals granulite facies metamorphic ages of ca. 595–602 Ma. However, a few zircons yield relatively older apparent 206Pb/238U ages of ca. 620 Ma, representing prograde metamorphic age. ADMGs preserve mean zircon εHf (t) values of +7.0 to +9.7 and δ18O values of 6.1–8.0‰. Based on petrographic observations, geothermobarometric calculations using conventional thermobarometry, mineral equilibria modeling, Ti-in-zircon and Zr-in-rutile thermometers reveal peak granulite facies P–T conditions of 0.95–1.2 GPa/940–1000°C, and retrograde amphibolite facies conditions of 0.83–0.93 GPa/575–710°C. The prograde metamorphic stage is inferred to be amphibolite or eclogite facies metamorphism. Hence, a clockwise a P–T–t path is proposed for the ADMGs. The overall results indicate that ADMGs are ultra-high temperature (UHT) granulites, and the protolith is altered oceanic crust consumed during the Pan-African collisional events. Asthenospheric upwelling induced by lithospheric delamination in the earliest extension of the thickened orogen, or by slab break-off in the background of collision may have provided the additional heat for UHT granulite facies metamorphism.
Linking Selective Alteration, Mineral Compositional Zonation and Sulfide Melt Emplacement in Orogenic-Type Magmatic Ni–Cu Sulfide Deposits
Authors: Cui Meng-Meng , Su Ben-Xun , Wang Jing , Tang Dong-Mei , Sakyi Patrick Asamoah , Moynier Frédéric
Published: May 2022

The chemical characteristics of magmatic Ni–Cu sulfide deposits in orogenic settings differ from those in cratons as they are characterized by extensive alteration, presence of hydrous minerals and typical normal mantle sulfur isotopes. How these characteristics are related to the mode of formation of the Ni–Cu sulfide deposits is still unknown. Here, we present petrological and mineralogical investigations of the Hongqiling Ni–Cu sulfide deposit, a typical representative of such numerous deposits in the Central Asian Orogenic Belt. Observations at various scales of field outcrops, hand specimens, thin sections and microscopes reveal that alterations are selectively exposed in silicate minerals, particularly olivine and pyroxenes that are close to ore bodies and sulfides. Such selective alteration is also related to sulfide type and abundance, and ore texture in the rocks/ores. It is worth noting that alteration of olivine and pyroxenes becomes weak when hydrous minerals (hornblende and phlogopite) are present. Profile analyses demonstrate that the olivine grains enclosed in or in contact with sulfides have compositional zonation with Fe, Mn, Sc and Zn concentrations higher when closer to the contacts with sulfides relative to the cores and contacts with other silicates, while those grains in sulfide-barren rocks show relatively homogeneous compositions. Similarly, the hornblende grains in contact with sulfide show distinct compositional variations. Sulfides in the rocks and ores are all free of alteration and have mantle-like sulfur isotopic compositions (pyrrhotite δ34S = −1.53 to 0.38‰; pentlandite δ34S = −1.28 to 0.25‰; chalcopyrite δ34S = −1.77 to 0.24‰). These features suggest that the selective alterations occurring in early crystallized phases were induced by sulfide melt intrusion and crystallization, instead of late-stage processes as previously thought. The sulfide melts segregated at the early stage of the magma evolution were presumably hydrous and buoyant in the silicate magma and therefore were transported upward and penetrated into silicate grains. The hydrous fluids were independent of the subducted material and metamorphic origin, and contained no significant crustal component in the late Triassic. Finally, when the sulfides crystallized, fluids would be released from the sulfide melts to hydrate surrounding mineral phases and rocks, because sulfides theoretically don’t accommodate hydrous components. The fluids also enhanced compositional exchanges between sulfides and silicates and accounted for the crystallization of hydrous minerals. From this perspective, fluids play a critical role in sulfide melt transportation and silicate compositional alteration, and selective alteration can be considered as a significant indicator of mineralization and exploration in mafic-ultramafic intrusions.
Multilayered synergistic regulation of phytoalexin biosynthesis by ethylene, jasmonate, and MAPK signaling pathways in Arabidopsis
Authors: Zhou Jinggeng , Mu Qiao , Wang Xiaoyang , Zhang Jun , Yu Haoze , Huang Tengzhou , He Yunxia , Dai Shaojun , Meng Xiangzong
Published: May 2022

Camalexin, an indolic antimicrobial metabolite, is the major phytoalexin in Arabidopsis thaliana, and plays a crucial role in pathogen resistance. Our previous studies revealed that the Arabidopsis mitogen-activated protein kinases MPK3 and MPK6 positively regulate pathogen-induced camalexin biosynthesis via phosphoactivating the transcription factor WRKY33. Here, we report that the ethylene and jasmonate (JA) pathways act synergistically with the MPK3/MPK6–WRKY33 module at multiple levels to induce camalexin biosynthesis in Arabidopsis upon pathogen infection. The ETHYLENE RESPONSE FACTOR1 (ERF1) transcription factor integrates the ethylene and JA pathways to induce camalexin biosynthesis via directly upregulating camalexin biosynthetic genes. ERF1 also interacts with and depends on WRKY33 to upregulate camalexin biosynthetic genes, indicating that ERF1 and WRKY33 form transcriptional complexes to cooperatively activate camalexin biosynthetic genes, thereby mediating the synergy of ethylene/JA and MPK3/MPK6 signaling pathways to induce camalexin biosynthesis. Moreover, as an integrator of the ethylene and JA pathways, ERF1 also acts as a substrate of MPK3/MPK6, which phosphorylate ERF1 to increase its transactivation activity and therefore further cooperate with the ethylene/JA pathways to induce camalexin biosynthesis. Taken together, our data reveal the multilayered synergistic regulation of camalexin biosynthesis by ethylene, JA, and MPK3/MPK6 signaling pathways via ERF1 and WRKY33 transcription factors in Arabidopsis.
DETECTION OF TRANSGENERATIONAL GENETIC EFFECTS BASED ON WHOLE-GENOME SEQUENCING IN THE MOUSE MODEL
Authors: Gondo Yoichi
Published: May 2022

It has become feasible to detect de novo mutations in mammalian genomes by using whole-genome sequencing. The power to detect numbers of de novo mutations should provide a useful tool to assess the transgenerational genetic effects of radiations on living organisms. By reviewing the spontaneous mutations in the mouse as a model, an action plan is proposed to detect the induced mutations after accumulating mutations for several generations with continuous exposure to low-dose radiations. Some susceptibility differences against radiations between humans and model animals for the transgenerational effect have been suggested. The applicability of the mouse model for the assessment of low-dose radiation is also discussed.
Variant-to-gene-mapping analyses reveal a role for pancreatic islet cells in conferring genetic susceptibility to sleep-related traits
Authors: Lasconi Chiara , Pahl Matthew C , Pippin James A , Su Chun , Johnson Matthew E , Chesi Alessandra , Boehm Keith , Manduchi Elisabetta , Ou Kristy , Golson Maria L , Wells Andrew D , Kaestner Klaus H , Grant Struan F A
Published: May 2022

We investigated the potential role of sleep-trait associated genetic loci in conferring a degree of their effect via pancreatic α- and β-cells, given that both sleep disturbances and metabolic disorders, including type 2 diabetes and obesity, involve polygenic contributions and complex interactions. We determined genetic commonalities between sleep and metabolic disorders, conducting linkage disequilibrium genetic correlation analyses with publicly available GWAS summary statistics. Then we investigated possible enrichment of sleep-trait associated SNPs in promoter-interacting open chromatin regions within α- and β-cells, intersecting public GWAS reports with our own ATAC-seq and high-resolution promoter-focused Capture C data generated from both sorted human α-cells and an established human beta-cell line (EndoC-βH1). Finally, we identified putative effector genes physically interacting with sleep-trait associated variants in α- and EndoC-βH1cells running variant-to-gene mapping and establish pathways in which these genes are significantly involved. We observed that insomnia, short and long sleep—but not morningness—were significantly correlated with type 2 diabetes, obesity and other metabolic traits. Both the EndoC-βH1 and α-cells were enriched for insomnia loci (p = .01; p = .0076), short sleep loci (p = .017; p = .022) and morningness loci (p = 2.2 × 10−7; p = .0016), while the α-cells were also enriched for long sleep loci (p = .034). Utilizing our promoter contact data, we identified 63 putative effector genes in EndoC-βH1 and 76 putative effector genes in α-cells, with these genes showing significant enrichment for organonitrogen and organophosphate biosynthesis, phosphatidylinositol and phosphorylation, intracellular transport and signaling, stress responses and cell differentiation. Our data suggest that a subset of sleep-related loci confer their effects via cells in pancreatic islets.
Liechtenstein discretionary trusts: beneficiaries, be aware of your rights!
Authors: Gassner Martin
Published: May 2022

Be aware, the beneficiary principle as it is lived in Liechtenstein might not meet your expectations. Beneficiaries of a discretionary trust under the Principality’s jurisdiction could fall short of basic rights, which one would expect granted. These include the right to information and the right to file a motion with the court if one suspects that the trust has been administered in an incorrect manner—ie where allocation, distribution, administration and invoicing do not comply with the initial agreement. Liechtenstein law offers various options to meet the requirements of clients, however, take this article as good advice to apply particular care when drafting a trust deed.
Assessing the Financial Sustainability of High-Fidelity and Virtual Reality Simulation for Nursing Education
Authors: Bumbach Michael D. , Culross Beth A. , Datta Santanu K.
Published: May 2022

To stimulate classroom discussion and collaboration amid the COVID-19 pandemic, increasingly creative pedological methods for nursing education are necessary. Traditionally, high-fidelity simulation has been the standard for nursing education, but the use of virtual reality simulation is increasing. One of the major evaluative measures of simulation clinical training is the cost associated with each modality. In this retrospective case analysis, budget impact analysis methods were employed to compare high-fidelity simulation with virtual reality simulation. The components of each simulation pedagogy were compared in categorized cost buckets. Overall, virtual reality simulation education was determined to require 22% less time than high-fidelity simulation education. The cost associated with the virtual reality simulation was found to be 40% less expensive than the high-fidelity simulation. Our results demonstrate that virtual reality simulation is a financially advantageous, resource conscious pedagogical option for nursing education.