bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiviral treatment for hepatitis C is associated with a reduced risk of atherosclerotic cardiovascular outcomes: A systematic review and meta‐analysis
Authors: Su Xin , Zhao Xin , Deng Jia‐Long , Li Song‐Nan , Du Xin , Dong Jian‐Zeng , Ma Chang‐Sheng
Published: January 2021

Hepatitis C virus infection (HCV) may be associated with a greater risk of cardiovascular disease (CVD), and the evidence for whether antiviral therapy for HCV could reduce the risk of CVD events is inconsistent. The aim of this meta‐analysis was to investigate the association between anti‐HCV treatment and the risk of CVD. We searched PubMed, EMBASE and Cochrane Library databases from inception to 20 August 2020. The pooled hazard ratio (HR) with 95% confidence interval (CI) of the risk of CVD events [any CVD, coronary artery disease (CAD) and stroke] was calculated using the random‐effects model. A total of eleven studies, including 309,470 subjects, were enrolled in this meta‐analysis. Among those, four studies reported on any CVD between anti‐HCV–treated and anti‐HCV–untreated patients, five studies reported on CAD, and five studies reported on stroke. Also, five studies reported on any CVD between patients with sustained virological response (SVR) and without SVR. Overall, antiviral therapy for HCV was associated with a reduced risk of any CVD (HR = 0.64, 95% CI: 0.50–0.83), CAD (HR = 0.73, 95% CI: 0.55–0.96) and stroke (HR = 0.74, 95% CI: 0.64–0.86). Besides, we found that SVR was associated with a significant decrease in any CVD compared with non‐SVR (HR = 0.74, 95% CI: 0.60–0.92). In conclusion, this meta‐analysis demonstrated that antiviral therapy for HCV was associated with a reduced risk of CVD events. In addition, the risk of CVD events was lower in individuals with SVR compared with those without SVR.
Impact of maternal infection with hepatitis B virus on pregnancy complications and neonatal outcomes for women undergoing assisted reproductive technology treatment: A population‐based study
Authors: Xiong Yiquan , Liu Chunrong , Huang Shiyao , Wang Jing , Qi Yana , Yao Guanhua , Sun Wei , Qian Yongyao , Ye Lishan , Liu Hui , Xu Qiushi , Zou Kang , Tan Jing , Sun Xin
Published: January 2021

The aim of this study was to investigate the impact of maternal hepatitis B virus (HBV) status on pregnancy complications and neonatal outcomes for women undergoing assisted reproductive technology (ART). A total of 7,011 pregnancies achieved by ART were included from a population‐based database involving 523,111 pregnancies. Exposures of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) among pregnant women were routinely tested at the first antenatal visit for all pregnancies. We collected pregnancy complications (e.g., gestational diabetes mellitus [GDM], intrahepatic cholestasis of pregnancy [ICP]), neonatal outcomes and confounding variables from the same database. Univariate and multivariate analyses by adjusting confounders were conducted to evaluate the impact of maternal HBV infection. Prevalence of HBsAg seropositivity (HBsAg+) was 11.34% (95% CI 10.6–12.1) and that of HBsAg and HBeAg co‐seropositivity (HBsAg+HBeAg+) was 2.55% (2.1–3.0) among included population. Compared with HBsAg−group, ICP risk in the HBsAg+group was higher (4.03% vs. 1.79%; adjusted odds ratio [aOR] 2.49, 1.65−3.77). Similarly, ICP prevalence in the HBsAg+HBeAg+ group was higher than that in the HBsAg−HBeAg− group (6.47% vs. 1.61%; aOR 4.78, 2.28–9.98). No associations were found between maternal HBV infection (i.e., HBsAg+, HBsAg+HBeAg+, or HBsAg+HBeAg−) and other adverse outcomes for women undergoing ART (i.e., GDM, pre‐eclampsia, placental previa, premature separation of placenta, premature rupture of membranes, preterm birth and low birthweight) in this study. In conclusion, maternal HBV infection (HBsAg+or HBsAg+HBeAg+) probably increase ICP risk, but may not associate with other pregnancy complications or neonatal outcomes for pregnant women who underwent ART.
When I say … pedagogy
Authors: Dornan Tim , Kelly Martina
Published: January 2021

Dornan and Kelly explain why pedagogy is best thought of as "teachers forming educative relationships that create zones of proximal development in which students can learn to the best of their abilities".
Perceiving commitments: When we both know that you are counting on me
Authors: Bonalumi Francesca , Michael John , Heintz Christophe
Published: January 2021

Can commitments be generated without promises or gestures conventionally interpreted as such? We hypothesized that people believe that commitments are in place when one agent has led a recipient to rely on her to do something, even without a commissive speech act or any action conventionalized as such, and this is mutual knowledge. To probe this, we presented participants with online vignettes describing everyday situations in which a recipient's expectations were frustrated by one's behavior. Our results show that moral judgments differed significantly according to whether the recipient's reliance was mutually known, irrespective of whether this was verbally acknowledged.
Normative inferentialism on linguistic understanding
Authors: Drobňák Matej
Published: January 2021

The aim of this paper is to establish a specific view of linguistic understanding based on the framework of normative inferentialism. Normative inferentialism is presented as an overspecification (rich) account of meaning—the meaning of a sentence is understood as a cluster of context‐dependent contents. The standard psychological mechanism responsible for reaching understanding of an utterance depends on the ability to eliminate contextually irrelevant aspects/parts of meaning. The advantages of the view are that the mechanism can (a) explain a wide range of linguistic phenomena including polysemy, homonymy, and conversational implicatures, and (b) explain partial understanding of an utterance.
Hard ticks (Acari: Ixodidae) infesting domestic animals in Egypt: diagnostic characters and a taxonomic key to the collected species
Authors: Okely M. , Anan R. , Gad‐Allah S. , Samy A. M.
Published: January 2021

Ticks are important vectors of emerging health problems in humans and animals. We conducted several field surveillances to investigate the fauna of hard ticks on domestic animals in seven governorates of Egypt during 2018–2019. A total of 3265 individual tick specimens were collected and identified to the species level; the specimens belong to 11 species within three genera (Amblyomma, Hyalomma, and Rhipicephalus). Tick infestation was highest in dromedary camels (70%), followed by dogs (52.5%), cattle (50%), buffaloes (38%), and horses (12%). Ten species were collected from dromedary camels, 2 from cattle, and one species from dogs, buffaloes, and horses. Diagnostic characters with high‐quality photographic images of the 11 tick species were provided. New measurements of the body regions such as spiracles and body grooves were also obtained to provide further details on morphological variations among the diverse tick species. This study provided detailed descriptions of the genital apertures of five Hyalomma species. Morphological variations of male Hyalomma impeltatum, and genital apertures of female Hyalomma dromedarii and Hyalomma excavatum were also examined in this study. Finally, we provided additional details on local geographic distributions, hosts, endemicity status, and disease relationships of the eleven tick species.
Coordination of stem and leaf traits define different strategies to regulate water loss and tolerance ranges to aridity
Authors: López Rosana , Cano Francisco Javier , Martin‐StPaul Nicolas K. , Cochard Hervé , Choat Brendan
Published: January 2021

Adaptation to drought involves complex interactions of traits that vary within and among species. To date, few data are available to quantify within‐species variation in functional traits and they are rarely integrated into mechanistic models to improve predictions of species response to climate change.

We quantified intraspecific variation in functional traits of two Hakea species growing along an aridity gradient in southeastern Australia. Measured traits were later used to parameterise the model SurEau to simulate a transplantation experiment to identify the limits of drought tolerance.

Embolism resistance varied between species but not across populations. Instead, populations adjusted to drier conditions via contrasting sets of trait trade‐offs that facilitated homeostasis of plant water status. The species from relatively mesic climate, Hakea dactyloides, relied on tight stomatal control whereas the species from xeric climate, Hakea leucoptera dramatically increased Huber value and leaf mass per area, while leaf area index (LAI) and epidermal conductance (gmin) decreased. With trait variability, SurEau predicts the plasticity of LAI and gmin buffers the impact of increasing aridity on population persistence.

Knowledge of within‐species variability in multiple drought tolerance traits will be crucial to accurately predict species distributional limits.
Genome‐wide discovery of natural variation in pre‐mRNA splicing and prioritising causal alternative splicing to salt stress response in rice
Authors: Yu Huihui , Du Qian , Campbell Malachy , Yu Bin , Walia Harkamal , Zhang Chi
Published: January 2021

Pre‐mRNA splicing is an essential step for the regulation of gene expression. In order to specifically capture splicing variants in plants for genome‐wide association studies (GWAS), we developed a software tool to quantify and visualise Variations of Splicing in Population (VaSP).

VaSP can quantify splicing variants from short‐read RNA‐seq datasets and discover genotype‐specific splicing (GSS) events, which can be used to prioritise causal pre‐mRNA splicing events in GWAS. We applied our method to an RNA‐seq dataset with 328 samples from 82 genotypes from a rice diversity panel exposed to optimal and saline growing conditions.

In total, 764 significant GSS events were identified in salt stress conditions. GSS events were used as markers for a GWAS with the shoot Na+ accumulation, which identified six GSS events in five genes significantly associated with the shoot Na+ content. Two of these genes, OsNUC1 and OsRAD23 emerged as top candidate genes with splice variants that exhibited significant divergence between the variants for shoot growth under salt stress conditions.

VaSP is a versatile tool for alternative splicing analysis in plants and a powerful tool for prioritising candidate causal pre‐mRNA splicing and corresponding genomic variations in GWAS.
The maximum growth rate hypothesis is correct for eukaryotic photosynthetic organisms, but not cyanobacteria
Authors: Rees T. A. V. , Raven John A.
Published: January 2021

The (maximum) growth rate (µmax) hypothesis predicts that cellular and tissue phosphorus (P) concentrations should increase with increasing growth rate, and RNA should also increase as most of the P is required to make ribosomes.

Using published data, we show that though there is a strong positive relationship between the µmax of all photosynthetic organisms and their P content (% dry weight), leading to a relatively constant P productivity, the relationship with RNA content is more complex.

In eukaryotes there is a strong positive relationship between µmax and RNA content expressed as % dry weight, and RNA constitutes a relatively constant 25% of total P. In prokaryotes the rRNA operon copy number is the important determinant of the amount of RNA present in the cell. The amount of phospholipid expressed as % dry weight increases with increasing µmax in microalgae. The relative proportions of each of the five major P‐containing constituents is remarkably constant, except that the proportion of RNA is greater and phospholipids smaller in prokaryotic than eukaryotic photosynthetic organisms. The effect of temperature differences between studies was minor.

The evidence for and against P‐containing constituents other than RNA being involved with ribosome synthesis and functioning is discussed.
Plastidial retrograde modulation of light and hormonal signaling: an odyssey
Authors: Jiang Jishan , Dehesh Katayoon
Published: January 2021

The transition from an engulfed autonomous unicellular photosynthetic bacterium to a semiautonomous endosymbiont plastid was accompanied by the transfer of genetic material from the endosymbiont to the nuclear genome of the host, followed by the establishment of plastid‐to‐nucleus (retrograde) signaling. The retrograde coordinated activities of the two subcellular genomes ensure chloroplast biogenesis and function as the photosynthetic hub and sensing and signaling center that tailors growth‐regulating and adaptive processes. This review specifically focuses on the current knowledge of selected stress‐induced retrograde signals, genomes uncoupled 1 (GUN1), methylerythritol cyclodiphosphate (MEcPP), apocarotenoid and β‐cyclocitral, and 3′‐phosphoadenosine 5′‐phosphate (PAP), which evolved to establish the photoautotrophic lifestyle and are instrumental in the integration of light and hormonal signaling networks to ultimately fashion adaptive responses in an ever‐changing environment.
Genes derived from ancient polyploidy have higher genetic diversity and are associated with domestication in Brassica rapa
Authors: Qi Xinshuai , An Hong , Hall Tara E. , Di Chenlu , Blischak Paul D. , McKibben Michael T. W. , Hao Yue , Conant Gavin C. , Pires J. Chris , Barker Michael S.
Published: January 2021

Many crops are polyploid or have a polyploid ancestry. Recent phylogenetic analyses have found that polyploidy often preceded the domestication of crop plants. One explanation for this observation is that increased genetic diversity following polyploidy may have been important during the strong artificial selection that occurs during domestication.

In order to test the connection between domestication and polyploidy, we identified and examined candidate genes associated with the domestication of the diverse crop varieties of Brassica rapa. Like all ‘diploid’ flowering plants, B. rapa has a diploidized paleopolyploid genome and experienced many rounds of whole genome duplication (WGD). We analyzed transcriptome data of more than 100 cultivated B. rapa accessions.

Using a combination of approaches, we identified > 3000 candidate genes associated with the domestication of four major B. rapa crop varieties. Consistent with our expectation, we found that the candidate genes were significantly enriched with genes derived from the Brassiceae mesohexaploidy. We also observed that paleologs were significantly more diverse than non‐paleologs.

Our analyses find evidence for that genetic diversity derived from ancient polyploidy played a key role in the domestication of B. rapa and provide support for its importance in the success of modern agriculture.
High‐dose vitamin D during pregnancy and pathway gene polymorphisms in prevention of offspring persistent wheeze
Authors: Brustad Nicklas , Greve Jens H. , Mirzakhani Hooman , Pedersen Casper‐Emil T. , Eliasen Anders U. , Stokholm Jakob , Lasky‐Su Jessica , Bønnelykke Klaus , Litonjua Augusto A. , Weiss Scott T. , Bisgaard Hans , Chawes Bo L.
Published: January 2021

Background

Randomized controlled trials (RCTs) suggest a protective effect of high‐dose vitamin D supplementation in pregnancy on offspring risk of persistent wheeze, but only in some individuals, which might be explained by variations in vitamin D pathway genes. This study aimed to investigate the effect of vitamin D supplementation by maternal and offspring vitamin D receptor (VDR) genotype and GC genotype, encoding vitamin D binding protein (VDBP), in two RCTs.

Methods

In the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) RCT, we analyzed the effect of high‐dose vitamin D during pregnancy on the risk of persistent wheeze age 0‐3 years by variants in single nucleotide polymorphisms (SNPs) in VDR (rs1544410, rs2228570, rs7975128, rs7975232) and GC (rs4588, rs7041). Replication was sought in the Vitamin D Antenatal Asthma Reduction Trial (VDAART).

Results

In COPSAC2010, VDR SNP rs1544410 influenced the effect of high‐dose vitamin D: maternal Pinteraction = .049 and child Pinteraction = .001, with the largest effect in offspring from mothers with TT genotype: hazard ratio (95% CI), 0.26 (0.10‐0.68), P = .006, and no effect among CT or CC genotypes: 0.85 (0.48‐1.51), P = .58 and 0.94 (0.47‐1.89), P = .87, respectively. However, these findings were not replicated in VDAART. There was no significant effect modification from maternal or offspring GC genotype in either COPSAC2010 or VDAART: all Pinteraction ≥ .17.

Conclusions

We found that the effect of high‐dose vitamin D supplementation during pregnancy on offspring risk of persistent wheeze was significantly influenced by VDR genotype in the COPSAC2010 RCT, but not VDAART, which may be due to population differences.
Germline variants in exonic regions have limited impact on immune checkpoint blockade clinical outcomes in advanced melanoma
Authors: Montaudié Henri , Beranger Guillaume Emmanuel , Reinier Frédéric , Nottet Nicolas , Martin Hélène , Picard‐Gauci Alexandra , Troin Laura , Ballotti Robert , Passeron Thierry
Published: January 2021

Immune checkpoint inhibition (ICI) treatments improve outcomes for metastatic melanoma; however, up to 60% of treated patients do not respond to ICI and/or develop immune‐related adverse events (irAEs). Currently, robust and reliable biomarker to predict response and/or occurrence of irAEs to ICI are missing. Herein, we wanted to explore whether germline variants (SNPs) could predict the clinical outcomes of melanoma patients treated with ICIs. We performed a whole exome sequencing using gDNA isolated from blood, from a discovery cohort of 57 patients with metastatic melanoma. The top associations were then tested in a validation cohort of 57 patients. Our work suggests that individual germline genetic variants have no or weak impact on the response to ICIs. Only, variants in IL1RL1 have a significant impact in treatment response. The role of IL1RL1 in the immune response against melanoma and as a theranostic marker warrants further investigations.
Diverse actions of cord blood cell therapy for hypoxic‐ischemic encephalopathy
Authors: Sato Yoshiaki , Tsuji Masahiro
Published: January 2021

Perinatal hypoxic‐ischemic encephalopathy (HIE) is a major cause of neonatal death and permanent neurological deficits. However, effective treatments have not yet been established, except therapeutic hypothermia, which is not effective for severe HIE; therefore, developing a novel therapy for HIE is of the utmost importance. Stem cell therapy has recently been identified as a novel therapy for HIE. Among the various stem cell sources, ethical hurdles can be avoided by using stem cells that originate from non‐embryonic or non‐neural tissues, such as umbilical cord blood cells (UCBCs), which are readily available and can be exploited for autologous transplantations. Human UCBs are a rich source of stem and progenitor cells. Many recent studies have reported the treatment effect of UCBCs. Additionally, phase I clinical trials have already been conducted, showing this therapy’s safety and feasibility. One advantage of stem cell therapies, including UCBC administration, is that they exert treatment effects through multifaceted mechanisms. According to the findings of several publications, replacement of lost cells, namely, engraftment and differentiation into neuronal cells, is not likely to be the main mechanism. However, the association between UCBCs and various mechanism of action, such as neurogenesis, angiogenesis, and anti‐inflammation, has been suggested in many studies, and most mechanisms are due to growth factors secreted from UCBCs. These diverse actions of UCBC treatment are expected to exert a substantial effect on HIE, which has a complex injury mechanism.
Neutrophils from patients with the cardiac clinical form of Chagas disease release less NETs than neutrophils from healthy individuals
Authors: Duarte de Almeida Valéria , da Câmara Eduardo B. L. , Castro Marcelo Augusto A. , Pimenta Suyane Maria P. , Hernandes Bruna Luiza T. , Paiva Dayane Carla C. , Andrade Cléber M. , do Nascimento Ellany G. C. , Fernandes Thales Allyrio A. M. , Andrade Micássio F.
Published: January 2021

Introduction

Chagas disease (CD) is a global health concern with approximately 12 000 deaths per year worldwide. In the chronic phase, about 30% of patients develop the cardiac clinical form, which presents symptoms associated with the presence of inflammatory cells in the cardiac tissue. Neutrophils are inflammatory cells able to modulate the chronic immune response against pathogens. These cells are capable of interacting with Trypanosoma cruzi, the aetiological agent of CD, and perform several effector functions, such as NET release. However, few studies have been carried out to investigate the role of these cells in the disease.

Aims

To investigate the release of NETs by neutrophils from CD patients by measuring the amount of DNA and elastase released.

Methods and results

Measurement of DNA release by neutrophils from chronic CD patients presenting the indeterminate (IND group; n = 18) and cardiac (CARD group; n = 15) clinical forms and nonchagasic subjects (n = 18) stimulated with soluble antigen of T. cruzi was quantified using the Quant‐iT™ PicoGreen® dsDNA assay kit. Patients from CARD group release less DNA (117.3 ± 21.85 ng/mL; *P = .0131) than neutrophils from control (177.7 ± 58.41 ng/mL). Elastase enzyme degranulation was measured using the substrate N‐methoxysuccinyl‐Ala‐Ala‐Pro‐Val p‐nitroanilide (SAAVNA). Absorbance values of elastase degranulation activity showed that only cells from healthy individuals presented a high release profile of elastase. Also, we found a negative correlation between DNA released concentration and risk of death (r = −.6574; *P = .0173); the lower the neutrophil DNA release from chagasic patients with cardiac event, the higher the risk of death.

Conclusion

These preliminary data show that patients with the cardiac form of CD release less NETs than nonchagasic individuals, raising the possibility that lower release of NETs enhances risk of death in CD patients with cardiac events.
Population structure of Phytophthora infestans in Turkey reveals expansion and spread of dominant clonal lineages and virulence
Authors: Göre Mehmet E. , Altın Nedim , Myers Kevin , Cooke David E. L. , Fry William E. , Özer Göksel
Published: January 2021

Late blight, caused by the oomycete Phytophthora infestans, is considered the most important and destructive disease of potato in Turkey. In this study, characterization of 367 isolates of P. infestans obtained from the potato‐growing areas of the country was carried out to evaluate the pathogen population structure over the 2017–2019 production seasons. The isolates were characterized by numerous features including mating type, in vitro mefenoxam sensitivity, simple‐sequence repeat (SSR) markers, and virulence against a set of potato differential lines. Most isolates were A2 mating type (353 isolates). Also, 68% of isolates were resistant to mefenoxam; the remainder were intermediate in their sensitivity and there were no sensitive isolates. SSR‐based genotypic analysis of P. infestans populations showed a low genetic diversity. The 13_A2 clonal lineage predominated with a frequency of 92.1%, followed by 34_A1 (3.3%) and 37_A2 (2.7%). Genotypes 34_A1 and 37_A2 were detected only in 2019. This is the first report of 34_A1 and 37_A2 clonal lineages causing late blight disease of potato in Turkey. The most abundant virulence type was one overcoming resistance genes R1, R2, R3, R4, R6, R7, R10, and R11. These results emphasized that the migration of individuals and the asexual generation of subclonal differences were the main factors driving the population structure of P. infestans in Turkey.
Taking context to heart: Momentary emotions, menstrual cycle phase, and cardiac autonomic regulation
Authors: Simon Shauna G. , Sloan Richard P. , Thayer Julian F. , Jamner Larry D.
Published: January 2021

Emotions have long been discussed in conjunction with the autonomic nervous system. Most research on emotion‐autonomic linkages does not consider sex differences or an evident underlying mechanism for sex differences: menstrual cycle phase. Further, most research is limited to cross‐sectional and laboratory studies. The degree to which emotion‐autonomic associations manifest in everyday life may be different and may vary by sex and, for women, by menstrual cycle phase. This study employs the ambulatory monitoring of cardiovascular measures (e.g., heart rate and heart rate variability; HRV) and concurrent emotional states (e.g., sadness, stress, anxiety, anger, and happiness) in everyday life to better characterize emotion‐autonomic associations as a function of sex and menstrual cycle phase. Participants (N = 174; 87 female) ages 18 to 46 (31.23 ± 6.49) were monitored over a 5‐day observation period (one 2‐ and one 3‐day session), using an ambulatory 24‐hour electrocardiogram to monitor heart rate and ecological momentary assessment to record emotions every ~30 min. Women were monitored in both the early to mid‐follicular and ‐luteal phases and men in two comparably distanced sessions. Multilevel models indicated that across sex, negative emotions and happiness were associated with elevated heart rate. Relative to men, women exhibited an elevated heart rate and reduced HRV during reports of anger. For women, during the luteal phase, but not follicular phase, momentary sadness, stress, and anxiety predicted increased heart rate and reduced HRV. These findings demonstrate the importance of considering sex and menstrual cycle phase in research investigating emotion‐autonomic linkages.
Bifurcations of thresholds in essential spectra of elliptic operators under localized non‐Hermitian perturbations
Authors: Borisov D. I. , Zezyulin D. A. , Znojil M.
Published: January 2021

We consider the operator
urn:x-wiley:00222526:media:sapm12367:sapm12367-math-0001subject to the Dirichlet or Robin condition, where a domain is bounded or unbounded. The symbol stands for a second‐order self‐adjoint differential operator on such that the spectrum of the operator contains several discrete eigenvalues , . These eigenvalues are thresholds in the essential spectrum of the operator . We study how these thresholds bifurcate once we add a small localized perturbation to the operator , where is a small positive parameter and is an abstract, not necessarily symmetric operator. We show that these thresholds bifurcate into eigenvalues and resonances of the operator in the vicinity of for sufficiently small . We prove effective simple conditions determining the existence of these resonances and eigenvalues and find the leading terms of their asymptotic expansions. Our analysis applies to generic nonself‐adjoint perturbations and, in particular, to perturbations characterized by the parity‐time () symmetry. Potential applications of our result embrace a broad class of physical systems governed by dispersive or diffractive effects. As a case example, we employ our findings to develop a scheme for a controllable generation of non‐Hermitian optical states with normalizable power and real part of the complex‐valued propagation constant lying in the continuum. The corresponding eigenfunctions can be interpreted as an optical generalization of bound states embedded in the continuum. For a particular example, the persistence of asymptotic expansions is confirmed with direct numerical evaluation of the perturbed spectrum .
The depositional signature of high‐aggradation chute‐and‐pool bedforms: The build‐and‐fill structure
Authors: Slootman Arnoud , Vellinga Age J. , Moscariello Andrea , Cartigny Matthieu J. B.
Published: January 2021

Chutes‐and‐pools are hybrid bedforms that occur in upper‐flow‐regime conditions, populating the stability field between antidunes and cyclic steps. Chutes‐and‐pools consist of a superimposition of a train of antidunes on a longer‐wavelength cyclic‐step instability. The presence of a hydraulic jump is more persistent in chutes‐and‐pools than the bores occasionally seen on breaking‐wave antidunes, yet not permanent as over cyclic‐step bedforms. The nature of chute‐and‐pool structures preserved in the depositional record is controlled largely by aggradation rate. This paper documents chute‐and‐pool structures generated beneath highly aggradational sediment density‐flows at the subaqueous toe‐of‐slope of a Pleistocene carbonate wedge. Quarry exposures enable the morphodynamic reconstruction of the sediment‐bed configuration that produced the identified structures. Wave‐breaking on growing antidunes occurred without the destruction of the antidune, which deviates from observations in low‐aggradation subaerial open‐channel flows. The antidune build‐up was followed by hydraulic jump controlled deposition in the antidune trough. Two‐dimensional depth‐resolved numerical simulations have been used to validate this process interpretation. The term aggradational chutes‐and‐pools is proposed for these bedforms, associated with the formation of build‐and‐fill structures consisting of interstratified convex lenses (in‐phase wave regime) and concave lenses (hydraulic jump regime). Such structures contrast with the scour‐and‐fill structures produced by low‐aggradation chutes‐and‐pools frequently described from subaerial open‐channel‐flow deposits. This study demonstrates a potential difference in flow behaviour between open‐channel flows and density flows in the supercritical regime.
Targeted caspofungin prophylaxis for invasive aspergillosis in high‐risk liver transplant recipients, a single‐center experience
Authors: Chakravarti Arpita , Butler‐Laporte Guillaume , Carrier Francois Martin , Bilodeau Marc , Huard Genevieve , Corsilli Daniel , Savard Patrice , Luong Me‐Linh
Published: January 2021

Background

Invasive aspergillosis (IA) is a rare but highly lethal complication after orthotopic liver transplantation (OLT). Targeted antifungal prophylaxis has been proposed as a strategy to prevent IA among orthotopic liver transplant recipient (OLTr), but limited data are available to support its efficacy.

Method

We conducted a single‐center, retrospective, before and after cohort study, comparing IA incidences among OLTr who did not receive antifungal prophylaxis after transplantation (cohort 1) to OLTr who received targeted antifungal prophylaxis after liver transplantation (cohort 2). Patients in cohort 2 received caspofungin prophylaxis if they presented one of the following risk factors: retransplantation, acute liver failure, dialysis, or Aspergillus colonization prior to transplantation. The primary outcome was IA at 90 days after transplantation.

Results

A total of 391 OLTr were included in the study; 181 patients in the cohort 1 (no prophylaxis) and 210 patients in the cohort 2 (targeted prophylaxis). Among patients in cohort 2, 19% (40/ 210) were considered at high risk for IA and 85% (34/40) of those received caspofungin prophylaxis. The incidence of IA at 90 days was 3.3% (6/ 181) and 0.5% (1/ 210), in cohort 1 and 2, respectively (OR 0.14; 95%CI 0.01‐0.83; P = .03). Ninety‐day mortality was similar among the two cohorts (3.9% (7/181) and 2.4% (5/210) in cohort 1 and 2, respectively (OR 0.61; 95% 0.18‐1.93; P = .40)). The 90‐day mortality among the OLTs with IA was 71% (5/7).

Conclusion

Targeted caspofungin prophylaxis was associated with lower rate of IA.
Association between cytomegalovirus infection and allograft rejection in a large contemporary cohort of heart transplant recipients
Authors: Boutolleau David , Coutance Guillaume , Désiré Eva , Bouglé Adrien , Bréchot Nicolas , Leprince Pascal , Varnous Shaida
Published: January 2021

Background

Cytomegalovirus (CMV) infection remains a common complication after heart transplantation (HTx). The association between CMV infection and allograft rejection is debated in the era of efficient prophylactic antiviral therapies.

Methods

This single‐center cohort study utilized a highly phenotyped database of HTx recipients (2012‐2016). The primary endpoint was the analysis of the association between CMV infection (CMV load ≥ 500 IU/mL whole blood) and the risk of allograft rejection (cellular rejection ≥ 1R1B, antibody‐mediated rejection ≥ pAMR1). Secondary endpoints included the analysis of a higher CMV load threshold (≥10 000 IU/mL) and different risk periods after PCR positivity. A mixed‐effect logistic regression model with a random intercept was applied. Results were adjusted for important risk factors of rejection.

Results

Overall, 384 patients were included and 6388 CMV loads and 3,494 endomyocardial biopsies were analyzed. CMV infections ≥ 500 IU/mL were diagnosed on 1223 (19.2%) blood samples from 284 (72.1%) patients and allograft rejections on 246 biopsies (7%) from 149 patients (38.8%). We did not find any association between CMV infection ≥ 500 IU/mL and rejection (univariable: OR 0.94, 95% CI [0.61, 1.45], P = .78, multivariable: OR 0.86, 95% CI [0.55, 1.33], P = .85). These results were consistent when analyzing a higher CMV load threshold and different periods of risk, reinforced by internal validation procedures and a posteriori calculation of the power (primary endpoint: power = 0.82, 95% CI [0.79‐0.84]) and reproducible across different clinical scenarios.

Conclusions

CMV infection was not associated with an increased risk of rejection in a contemporary cohort of HTx recipients.
Emb15 encodes a plastid ribosomal assembly factor essential for embryogenesis in maize
Authors: Xu Chunhui , Shen Yun , Li Cuiling , Lu Fan , Zhang Meng‐Di , Meeley Robert B. , McCarty Donald R. , Tan Bao‐Cai
Published: January 2021

Ribosome assembly factors guide the complex process by which ribosomal proteins and the ribosomal RNAs form a functional ribosome. However, the assembly of plant plastid ribosomes is poorly understood. In the present study, we discovered a maize (Zea mays) plastid ribosome assembly factor based on our characterization of the embryo defective 15 (emb15) mutant. Loss of function of Emb15 retards embryo development at an early stage, but does not substantially affect the endosperm, and causes an albino phenotype in other genetic backgrounds. EMB15 localizes to plastids and possesses a ribosome maturation factor M (RimM) domain in the N‐terminus and a predicted UDP‐GlcNAc pyrophosphorylase domain in the C‐terminus. The EMB15 RimM domain originated in bacteria and the UDP‐GlcNAc pyrophosphorylase domain originated in fungi; these two domains came together in the ancestor of land plants during evolution. The N‐terminus of EMB15 complemented the growth defect of an Escherichia coli strain with a RimM deletion and rescued the albino phenotype of emb15 homozygous mutants. The RimM domain mediates the interaction between EMB15 and the plastid ribosomal protein PRPS19. Plastid 16S rRNA maturation is also significantly impaired in emb15. These observations suggest that EMB15 functions in maize seed development as a plastid ribosome assembly factor, and the C‐terminal domain is not important under normal conditions.
Emerging patterns in phylogenetic studies of trichomycterid catfishes (Teleostei, Siluriformes) and the contribution of Andean diversity
Authors: Fernandez Luis , Arroyave Jairo , Schaefer Scott A.
Published: January 2021

Consensus is emerging among studies using DNA sequence data addressing problems in the taxonomy and relationships of trichomycterid catfishes, a dominant component of the Neotropical freshwater ichthyofauna, that have heretofore eluded efforts based on morphological data alone. No previous studies using molecular data have included representatives of Hatcheria and Silvinichthys, and none have included dense representation of the diverse Andean species of Trichomycterus. This study assembled both available and novel comparative DNA sequence data inclusive of Hatcheria, Silvinichthys, and additional Trichomycterus species not represented in previous studies to form the most taxonomically comprehensive molecular dataset of the Trichomycterinae at the genus level to date. Our results confirm previous findings of strong support for a monophyletic subfamily Trichomycterinae while rejecting the monophyly of its most diverse genus, Trichomycterus. Our results do not corroborate Trichomycterinae split into two reciprocally monophyletic groups, and we show strong support for a sister‐group relationship between Eremophilus mutisii and Trichomycterus bogotensis that suggests some degree of evolutionary distinctiveness for this clade of Colombian‐endemic species. Within Trichomycterus, we uncovered a novel clade of central Andean species and reveal a close relationship among southern Andean taxa that included a non‐monophyletic Silvinichthys, Bullockia, Hatcheria, plus a number of Trichomycterus species. Our results are broadly congruent with recent studies that have uncovered rampant polyphyly within the genus Trichomycterus and provide emerging evidence, as a result of increased taxonomic representation, for geographically circumscribed subclades of Trichomycterus species. Nevertheless, the widespread low support and resolution at most basal nodes pose a considerable challenge in understanding major patterns of intergeneric relationships, which in turn hinders our efforts to shed critical light on the biogeographic history of the group.
Platelet releasate normalises the compromised muscle regeneration in a mouse model of hyperlipidaemia
Authors: Barlow Joseph , Sfyri Pagona Panagiota , Mitchell Rob , Verpoorten Sandrine , Scully David , Andreou Charalampos , Papadopoulos Petros , Patel Ketan , Matsakas Antonios
Published: January 2021

New Findings

What is the central question of this study?

What is the impact of obesity‐independent hyperlipidaemia on skeletal muscle stem cell function of ApoE‐deficient (ApoE–/–) mice?

What is the main finding and its importance?

Compromised muscle stem cell function accounts for the impaired muscle regeneration in hyperlipidaemic ApoE–/– mice. Importantly, impaired muscle regeneration is normalised by administration of platelet releasate.

Muscle satellite cells are important stem cells for skeletal muscle regeneration and repair after injury. ApoE‐deficient mice, an established mouse model of hyperlipidaemia and atherosclerosis, show evidence of oxidative stress‐induced lesions and fat infiltration in skeletal muscle followed by impaired repair after injury. However, the mechanisms underpinning attenuated muscle regeneration remain to be fully defined. Key to addressing the latter is to understand the properties of muscle stem cells from ApoE‐deficient mice and their myogenic potential. Muscle stem cells from ApoE‐deficient mice were cultured both ex vivo (on single fibres) and in vitro (primary myoblasts) and their myogenic capacity was determined. Skeletal muscle regeneration was studied on days 5 and 10 after cardiotoxin injury. ApoE‐deficient muscle stem cells showed delayed activation and differentiation on single muscle fibres ex vivo. Impaired proliferation and differentiation profiles were also evident on isolated primary muscle stem cells in culture. ApoE‐deficient mice displayed impaired skeletal muscle regeneration after acute injury in vivo. Administration of platelet releasate in ApoE‐deficient mice reversed the deficits of muscle regeneration after acute injury to wild‐type levels. These findings indicate that muscle stem cell myogenic potential is perturbed in skeletal muscle of a mouse model of hyperlipidaemia. We propose that platelet releasate could be a therapeutic intervention for conditions with associated myopathy such as peripheral arterial disease.
Danthron attenuates experimental atherosclerosis by targeting foam cell formation
Authors: Shi Xiujin , Zhang Yi , Lin Baidi , Zhou Yang , Suo Wei , Wei Juanjuan , Zhang Lin , Lin Jie , Xiao Fucheng , Zhao Limin , Lin Yang
Published: January 2021

New Findings

What is the central question of this study?

Does danthron alleviate experimental atherosclerosis by inhibiting the formation of foam cells?

What are the main findings and their importance?

Danthron improved serum lipid profiles and significantly reduced the atherosclerotic plaque areas and lipid accumulation in the aortic root of ApoE−/− mice. Danthron inhibited foam cell formation in oxidized low‐density lipoprotein‐induced RAW264.7 macrophages. Furthermore, danthron exerted its function in atherosclerosis at least partly through activating the AMP‐activated protein kinase–sirtuin 1 signalling pathway. These findings suggest that danthron has the potential to alleviate atherosclerosis.

Danthron, an ingredient isolated from Rheum palmatum L., has been revealed to reduce lipid accumulation in vitro. This study aimed to discover the effects of danthron on the development of atherosclerosis and to delineate the underlying mechanisms. For in vivo studies, male ApoE−/− mice were fed a high‐fat diet and orally treated with danthron (30 or 60 mg/kg/day) for 12 weeks. For in vitro studies, RAW264.7 cells were induced by oxidized low‐density lipoprotein (ox‐LDL, 50 μg/ml) for 48 h and subsequently administered danthron at appropriate concentrations for 24 h. AMP‐activated protein kinase (AMPK) inhibitor compound C was added to ox‐LDL‐stimulated RAW264.7 cells 2 h before danthron administration to confirm the role of the AMPK signalling pathway in the regulation by danthron of foam cell formation. We found that danthron improved serum lipid profiles, and significantly reduced atherosclerotic plaque areas and lipid accumulation in the aortic root of atherosclerotic mice. Moreover, danthron upregulated the mRNA and protein expression of ATP‐binding cassette transporter A1 (ABCA1), ABCG1 and liver X receptor α (LXRα), which play a crucial role in lipid metabolism, and activated the AMPK–sirtuin 1 (SIRT1) pathway. In an in vitro study, danthron inhibited foam cell formation in ox‐LDL‐induced RAW264.7 macrophages with an increase in the expression of ABCA1, ABCG1 and LXRα as well as activation of the AMPK–SIRT1 pathway. Furthermore, compound C abolished the effects of danthron on lipid accumulation and the protein expression of ABCA1/G1 and LXRα in vitro. Our results highlight that danthron possesses potential benefits in alleviating experimental atherosclerosis by targeting foam cell formation by activating the AMPK–SIRT1 signalling pathway.
Regional functional and structural abnormalities within the aorta as a potential driver of vascular disease in metabolic syndrome
Authors: Ameer Omar Z. , Salman Ibrahim M. , Alwadi Aiman Y. , Ouban Abderrahman , Abu‐Owaimer Fahmi M. , AlSharari Shakir D. , Bukhari Ishfaq A.
Published: January 2021

New Findings

What is the central question of this study?

Is aortic dysfunction, a significant contributor to cardiovascular disease in metabolic syndrome, expressed uniformly across both the thoracic and abdominal aorta?

What is the main finding and its importance?

Our study shows that, in the setting of metabolic syndrome, functional and structural deficits in the aorta are differentially expressed along its length, with the abdominal portion displaying more extensive vascular abnormalities. It is, therefore, likely that early interventional strategies targeting the abdominal aorta might alleviate cardiovascular pathologies driven by the metabolic syndrome.

The extent of vascular dysfunction associated with metabolic syndrome might vary along the length of the aorta. In this study, we investigated regional functional and structural changes in the thoracic and abdominal aorta of a rat model of metabolic syndrome, namely, high‐fat diet (HFD) streptozotocin‐induced diabetes mellitus (HFD‐D). Four‐week‐old male Wistar albino rats were fed with either HFD or control diet (CD) for 10 weeks. At week 6, 40 mg/kg streptozotocin and its vehicle were injected i.p. into HFD and CD groups, respectively. At the end of the feeding period, rats were euthanised and aortic segments collected for assessment of vascular functional responses and histomorphometry. Tail‐cuff systolic blood pressures (154 ± 6  vs. 110 ± 4 mmHg) and areas under the curve for oral glucose and i.p. insulin tolerance tests were greater in HFD‐D versus CD rats. Abdominal aortic vasoconstriction in response to noradrenaline and KCl was greater in HFD‐D compared with CD rats. Thoracic vasoconstrictor responses to noradrenaline, but not KCl, were greater in the HFD‐D group. Abdominal, but not thoracic, endothelium‐dependent vasorelaxation in response to acetylcholine was blunted in HFD‐D relative to CD rats; however, nitric oxide‐dependent vasorelaxation in HFD‐D rats was impaired in both thoracic and abdominal segments. The abdominal aorta of HFD‐D rats showed deranged interlamellar spacing and increased lipid plaque deposition. In conclusion, vascular dysfunction in metabolic syndrome is expressed differentially along the length of the aorta, with the abdominal aorta exhibiting increased susceptibility to vasoconstrictors and greater deficits in endothelium‐dependent relaxation. These vascular functional abnormalities could potentially underlie the development of hypertensive cardiovascular disease associated with the metabolic syndrome.
Location, location, location: the organization and roles of potassium channels in mammalian motoneurons
Authors: Deardorff Adam S. , Romer Shannon H. , Fyffe Robert E.W.
Published: January 2021

The spatial and temporal balance of spinal α‐motoneuron (αMN) intrinsic membrane conductances underlies the neural output of the final common pathway for motor commands. Although the complete set and precise localization of αMN K+ channels and their respective outward conductances remain unsettled, important K+ channel subtypes have now been documented, including Kv1, Kv2, Kv7, TASK, HCN and SK isoforms. Unique kinetics and gating parameters allow these channels to differentially shape and/or modify αMN firing properties, and recent immunohistochemical localization of K+‐channel complexes reveals a framework in which their spatial distribution and/or focal clustering within different surface membrane compartments is highly tuned to their physiological function. Moreover, highly evolved regulatory mechanisms enable specific channels to operate over variable levels of αMN activity and contribute to either state‐dependent enhancement or diminution of firing. While recent data suggest an additional, non‐conducting role for clustered Kv2.1 channels in the formation of endoplasmic reticulum–plasma membrane junctions postsynaptic to C‐bouton synapses, electrophysiological evidence demonstrates that conducting Kv2.1 channels effectively regulate αMN firing, especially during periods of high activity in which the cholinergic C‐boutons are engaged. Intense αMN activity or cell injury rapidly disrupts the clustered organization of Kv2.1 channels in αMNs and further impacts their physiological role.
Thus, αMN K+ channels play a critical regulatory role in motor processing and are potential therapeutic targets for diseases affecting αMN excitability and motor output, including amyotrophic lateral sclerosis.

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