bluuebunny/crossref_metadata_2025 huggingface dataset:
Pre-pouch Ileitis is Associated with Development of Crohn’s Disease-like Complications and Pouch Failure
Authors: Syal Gaurav , Shemtov Ron , Bonthala Nirupama , Vasiliauskas Eric A , Feldman Edward J , Zaghiyan Karen , Ha Christina Y , McGovern Dermot P B , Targan Stephan R , Melmed Gil Y , Fleshner Phillip R
Published: December 2020

Background and Aims

It is unclear whether pre-pouch ileitis heralds an aggressive inflammatory pouch disease in patients with ileal pouch-anal anastomosis [IPAA]. We compared outcomes of patients with pouchitis and concomitant pre-pouch ileitis with those with pouchitis alone.

Methods

Patients undergoing IPAA surgery for inflammatory bowel disease, who subsequently developed pouchitis with concomitant pre-pouch ileitis [pre-pouch ileitis group], were matched by year of IPAA surgery and preoperative diagnosis [ulcerative colitis or inflammatory bowel disease-unclassified] with patients who developed pouchitis alone [pouchitis group]. Primary outcomes were development of Crohn’s disease [CD]-like complications [non-anastomotic strictures or perianal disease >6 months after ileostomy closure] and pouch failure. Secondary outcomes were need for surgical/endoscopic interventions and immunosuppressive therapy. Log-rank testing was used to compare outcome-free survival, and Cox regression was performed to identify predictors of outcomes.

Results

There were 66 patients in each group. CD-like complications and pouch failure developed in 36.4% and 7.6% patients in the pre-pouch ileitis group and 10.6% and 1.5% in pouchitis group, respectively. CD-like complications-free survival [log-rank p = 0.0002] and pouch failure-free survival [log-rank p = 0.046] were significantly lower in the pre-pouch ileitis group. The pre-pouch ileitis group had a higher risk of requiring surgical/endoscopic interventions [log-rank p = 0.0005] and immunosuppressive therapy [log-rank p <0.0001]. Pre-pouch ileitis was independently associated with an increased risk of CD-like complications (hazard ratio [HR] 3.8; p = 0.0007), need for surgical/endoscopic interventions [HR 4.1; p = 0.002], and immunosuppressive therapy [HR 5.0; p = 0.0002].

Conclusions

Pre-pouch ileitis is associated with a higher risk of complicated disease and pouch failure than pouchitis. It should be considered a feature of CD.
Differences in baseline characteristics and outcomes of bicuspid and tricuspid aortic valves in surgical aortic valve replacement
Authors: Çelik Mevlüt , Milojevic Milan , Durko Andras P , Oei Frans B.S , Bogers Ad. J.J.C , Mahtab Edris A.F
Published: December 2020

OBJECTIVES

Patients with bicuspid aortic valve (BAV) comprise a substantial portion of patients undergoing surgical aortic valve replacement (SAVR). Our goal was to quantify the prevalence of BAV in the current SAVR ± coronary artery bypass grafting (CABG) population, assess differences in cardiovascular risk profiles and assess differences in long-term survival in patients with BAV compared to patients with tricuspid aortic valve (TAV).

METHODS

Patients who underwent SAVR with or without concomitant CABG and who had a surgical report denoting the relevant valvular anatomy were eligible and included. Prevalence, predictors and outcomes for patients with BAV were analysed and compared to those patients with TAV. Matched patients with BAV and TAV were compared using a propensity score matching strategy and an age matching strategy.

RESULTS

A total of 3723 patients, 3145 of whom (mean age 66.6 ± 11.4 years; 37.4% women) had an operative report describing their aortic valvular morphology, underwent SAVR ± CABG between 1987 and 2016. The overall prevalence of patients with BAV was 19.3% (607). Patients with BAV were younger than patients with TAV (60.6 ± 12.1 vs 68.0 ± 10.7, respectively). In the age-matched cohort, patients with BAV were less likely to have comorbidities, among others diabetes (P = 0.001), hypertension (P < 0.001) and hypercholesterolaemia (P = 0.003), compared to patients with TAV. Twenty-year survival following the index procedure was higher in patients with BAV (14.8%) compared to those with TAV (12.9%) in the age-matched cohort (P = 0.015).

CONCLUSIONS

Substantial differences in the cardiovascular risk profile exist in patients with BAV and TAV. Long-term survival after SAVR in patients with BAV is satisfactory.
Vertical stratification patterns of methanotrophs and their genetic controllers in water columns of oxygen-stratified boreal lakes
Authors: Rissanen Antti J , Saarela Taija , Jäntti Helena , Buck Moritz , Peura Sari , Aalto Sanni L , Ojala Anne , Pumpanen Jukka , Tiirola Marja , Elvert Marcus , Nykänen Hannu
Published: December 2020

The vertical structuring of methanotrophic communities and its genetic controllers remain understudied in the water columns of oxygen-stratified lakes. Therefore, we used 16S rRNA gene sequencing to study the vertical stratification patterns of methanotrophs in two boreal lakes, Lake Kuivajärvi and Lake Lovojärvi. Furthermore, metagenomic analyses were performed to assess the genomic characteristics of methanotrophs in Lovojärvi and the previously studied Lake Alinen Mustajärvi. The methanotroph communities were vertically structured along the oxygen gradient. Alphaproteobacterial methanotrophs preferred oxic water layers, while Methylococcales methanotrophs, consisting of putative novel genera and species, thrived, especially at and below the oxic-anoxic interface and showed distinct depth variation patterns, which were not completely predictable by their taxonomic classification. Instead, genomic differences among Methylococcales methanotrophs explained their variable vertical depth patterns. Genes in clusters of orthologous groups (COG) categories L (replication, recombination and repair) and S (function unknown) were relatively high in metagenome-assembled genomes representing Methylococcales clearly thriving below the oxic-anoxic interface, suggesting genetic adaptations for increased stress tolerance enabling living in the hypoxic/anoxic conditions. By contrast, genes in COG category N (cell motility) were relatively high in metagenome-assembled genomes of Methylococcales thriving at the oxic-anoxic interface, which suggests genetic adaptations for increased motility at the vertically fluctuating oxic-anoxic interface.
Survival of the fittest: how the rice microbial community forces Sarocladium oryzae into pathogenicity
Authors: Peeters K J , Audenaert K , Höfte M
Published: December 2020

The fungus Sarocladium oryzae (Sawada) causes rice sheath rot and produces the phytotoxins cerulenin and helvolic acid. Both toxins show antimicrobial activity but only helvolic acid production in the rice sheath correlates with virulence. Sarocladium oryzae isolates that differ in their toxin production were used to study their interaction with the rice culturable bacterial endophyte community. The diversity and community structure was defined in the edge of sheath rot lesions, followed by a null model-based co-occurrence analysis to discover pairwise interactions. Non-random pairs were co-cultured to study the nature of the interactions and the role of the toxins herein. Compared to healthy sheaths, endophyte diversity strongly increased when infected with the least virulent S. oryzae isolates producing low amounts of toxins. Virulent S. oryzae isolates did not affect diversity but caused strong shifts in species composition. The endophyte community of healthy rice plants was dominated by B. cereus. This bacterium was enriched in lesions produced by low-virulent S. oryzae isolates and caused hyphal lysis. Contrarily, helvolic acid producers eliminated this bacterium from the sheath endosphere. We conclude that S. oryzae needs to produce antibiotics to defend itself against antagonistic rice endophytes to successfully colonize and infect the rice sheath.
The effects of performance-based financing on neonatal health outcomes in Burundi, Lesotho, Senegal, Zambia and Zimbabwe
Authors: Gage Anna , Bauhoff Sebastian
Published: December 2020

Maternal and newborn care has been a primary focus of performance-based financing (PBF) projects, which have been piloted or implemented in 21 countries in sub-Saharan Africa since 2007. Several evaluations of PBF have demonstrated improvements to facility delivery or quality of care. However, no studies have measured the impact of PBF programmes directly on neonatal health outcomes in Africa, nor compared PBF programmes against another. We assess the impact of PBF on early neonatal health outcomes and associated health care utilization and quality in Burundi, Lesotho, Senegal, Zambia and Zimbabwe. We pooled Demographic and Health Surveys and Multiple Indicator Cluster Surveys and apply difference-in-differences analysis to estimate the effect of PBF projects supported by the World Bank on early neonatal mortality and low birthweight. We also assessed the effect of PBF on intermediate outputs that are frequently explicitly incentivized in PBF projects, including facility delivery and antenatal care utilization and quality, and caesarean section. Finally, we examined the impact among births to poor or high-risk women. We found no statistically significant impact of PBF on neonatal health outcomes, health care utilization or quality in a pooled sample. PBF was also not associated with better health outcomes in each country individually, though in some countries and among poor women PBF improved facility delivery, antenatal care utilization or antenatal care quality. There was no improvement on the health outcomes among poor or high-risk women in the five countries. PBF had no impact on early neonatal health outcomes in the five African countries studied and had limited and variable effects on the utilization and quality of neonatal health care. These findings suggest that there is a need for both a deeper assessment of PBF and for other strategies to make meaningful improvements to neonatal health outcomes.
Baranov's contributions to the Beverton–Holt model
Authors: Kenchington Trevor J
Published: December 2020

The core of Beverton and Holt’s seminal work of the 1950s had been anticipated by Baranov 30 years earlier, but his contributions, published in Russian, remained poorly known to Anglophone scientists until after 1945. By that time, Russell and Graham had presented parallel ideas, though without Baranov’s mathematics. Limited subsequent acknowledgement of the Russian’s contributions has left an impression that each of his advances was achieved independently in England, hence that they contributed little to the Beverton–Holt model. I here construct a timeline of events linking and separating the Russian and English studies. From it, I argue that both Russell’s presentation of the underlying concepts and Graham’s decision to pursue a mathematical realization of his “Modern Theory” may have been influenced by translations of Baranov’s papers. Moreover, when Holt developed the “simple” Beverton–Holt model during 1946–1947, he certainly drew on Baranov’s exponential model of mortality, though perhaps only via Ricker.
Using Wood’s glass to enhance the efficiency of a water solar disinfection (SODIS) apparatus with a Fresnel lens
Authors: Alkhalidi Ammar , Arabasi Sameer , Othman Abeer Abu , Sabanikh Tareq , Mahmood Linda , Abdelal Qasem
Published: December 2020

Solar disinfection, as a low carbon technology, is a sustainable and cost-effective water treatment method, which makes it more likely to be implemented in developing countries. It has been proven that ultraviolet light radiation is effective against pathogens and microorganisms. The aim of this paper is to evaluate the performance of solar disinfection apparatus that is equipped with Wood’s glass and a Fresnel lens. Wood’s glass is a band-pass filter that allows ultraviolet light to go through and blocks most of the remaining spectrum including infrared. This serves a dual purpose. It lets through the part that inactivates pathogens and microorganisms (ultraviolet) and blocks the part that helps the growth of bacteria (infrared). Experimental setup is designed to investigate the effect of Wood’s glass with and without a Fresnel lens on the solar disinfection process. The investigation is done on a batch-based system and on a novel instantaneous water disinfection system. Results of water disinfection process were recorded for each set of experiments taking into considerations vital parameters, such as solar radiation, solar ultraviolet light intensity and water temperature. The results of these experiments showed effective water disinfection up to 85% pathogens removal by the use of daily available solar radiation.
On the Exceptional Sets of Integral Quadratic Forms
Authors: Chan Wai Kiu , Oh Byeong-Kweon
Published: December 2020

A collection $\mathcal S$ of equivalence classes of positive definite integral quadratic forms in $n$ variables is called an $n$-exceptional set if there exists a positive definite integral quadratic form, which represents all equivalence classes of positive definite integral quadratic forms in $n$ variables except those in $\mathcal S$. We show that, among other results, for any given positive integers $m$ and $n$, there is always an $n$-exceptional set of size $m$ and there are only finitely many of them.
Electronic consultations and clinician burnout: An antidote to our emotional pandemic?
Authors: Lee Michelle S , Nambudiri Vinod E
Published: December 2020

Health information technology is a major source of clinician burnout due to increased administrative burden and inefficient work processes. Electronic consultations (eConsults) represent a promising innovation to improve access to specialty care by reducing wait times for specialist visits and reducing unnecessary in-person specialist visits. While eConsults have clear benefits for patients and healthcare systems, their potential effects on provider burnout should be considered. Using a framework which outlines that the loss of autonomy, competence, and relatedness as the main contributing factors to clinician “amotivation” and burnout, we discuss the use of eConsults and their potential to mitigate or exacerbate burnout for primary care providers and specialists, as well as recommendations for implementation of eConsults to reduce burnout.
A sweet protein monellin as a non-antibody scaffold for synthetic binding proteins
Authors: Yasui Norihisa , Nakamura Kazuaki , Yamashita Atsuko
Published: December 2020

Synthetic binding proteins that have the ability to bind with molecules can be generated using various protein domains as non-antibody scaffolds. These designer proteins have been used widely in research studies, as their properties overcome the disadvantages of using antibodies. Here, we describe the first application of a phage display to generate synthetic binding proteins using a sweet protein, monellin, as a non-antibody scaffold. Single-chain monellin (scMonellin), in which two polypeptide chains of natural monellin are connected by a short linker, has two loops on one side of the molecule. We constructed phage display libraries of scMonellin, in which the amino acid sequence of the two loops is diversified. To validate the performance of these libraries, we sorted them against the folding mutant of the green fluorescent protein variant (GFPuv) and yeast small ubiquitin-related modifier. We successfully obtained scMonellin variants exhibiting moderate but significant affinities for these target proteins. Crystal structures of one of the GFPuv-binding variants in complex with GFPuv revealed that the two diversified loops were involved in target recognition. scMonellin, therefore, represents a promising non-antibody scaffold in the design and generation of synthetic binding proteins. We termed the scMonellin-derived synthetic binding proteins ‘SWEEPins’.
Homo religiosus: The Soul of Bioethics
Authors: Stempsey William E
Published: December 2020

Although many of the pioneers of present-day bioethics came from religious and theological backgrounds, the recent controversy about the role of religion in bioethics has elicited much attention. Timothy Murphy would ban religion from bioethics altogether. Much of the ado hinges on conflicting understandings of just what bioethics is and just what religion is. This paper attempts to make more explicit how the fields of bioethics and religion have been understood in this context, and how they should not be understood. We begin by looking at bioethics as a field: its origins, purpose, scope, and its methods. We then examine the notion of religion, looking especially at its importance for bioethics. Humanity is not just Homo sapiens but also Homo religiosus. Religion is more than a code of ethics; it gives insight into many of the foundational matters of bioethics.
Racial Disparities in Epigenetic Aging of the Right vs Left Colon
Authors: Devall Matthew , Sun Xiangqing , Yuan Fangcheng , Cooper Gregory S , Willis Joseph , Weisenberger Daniel J , Casey Graham , Li Li
Published: December 2020

There are well-documented racial differences in age-of-onset and laterality of colorectal cancer. Epigenetic age acceleration is postulated to be an underlying factor. However, comparative studies of side-specific colonic tissue epigenetic aging are lacking. Here, we performed DNA methylation analysis of matched right and left biopsies of normal colon from 128 individuals. Among African Americans (n = 88), the right colon showed accelerated epigenetic aging as compared with individual-matched left colon (1.51 years; 95% confidence interval [CI] = 0.62 to 2.40 years; 2-sided P = .001). In contrast, among European Americans (n = 40), the right colon shows remarkable age deceleration (1.93 years; 95% CI = 0.65 to 3.21 years; 2-sided P = .004). Further, epigenome-wide analysis of DNA methylation identifies a unique pattern of hypermethylation in African American right colon. Our study is the first to report such race and side-specific differences in epigenetic aging of normal colon, providing novel insight into the observed younger age-of-onset and relative preponderance of right-side colon neoplasia in African Americans.
Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients
Authors: Yasuda Koichi , Minatogawa Hideki , Dekura Yasuhiro , Takao Seishin , Tamura Masaya , Tsushima Nayuta , Suzuki Takayoshi , Kano Satoshi , Mizumachi Takatsugu , Mori Takashi , Nishioka Kentaro , Shido Motoyasu , Katoh Norio , Taguchi Hiroshi , Fujima Noriyuki , Onimaru Rikiya , Yokota Isao , Kobashi Keiji , Shimizu Shinichi , Homma Akihiro , Shirato Hiroki , Aoyama Hidefumi
Published: December 2020

Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.
‘Life communication’ after the 2011 Fukushima nuclear disaster: what experts need to learn from residential non-scientific rationality
Authors: Ochi Sae
Published: December 2020

After chemical, biological, radiological, nuclear or explosive (CBRNE) disasters, trepidation and infodemics about invisible hazards may cause indirect casualties in the affected society. Effective communication regarding technical issues between disaster experts and the residents is key to averting such secondary impacts. However, misconceptions about scientific issues and mistrust in experts frequently occur even with intensive and sincere communications. This miscommunication is usually attributed to residents’ conflicts with illiteracy, emotion, value depositions and ideologies. However, considering that communication is an interactive process, there are likely to be additional factors attributable to experts. This article aims to summarize the gaps in rationality between experts and residents observed after the 2011 Fukushima nuclear disaster to describe how residents perceived experts. There were discrepancies in the perception of ‘facts’, the perception of probability, the interpretation of risk comparison, what were included as risk trade-offs, the view of the disaster, whose behavior would be changed by the communication and whether risk should be considered a science. These findings suggest that there was a non-scientific rationality among residents, which often exercised a potent influence on everyday decision-making. It might not be residents but experts who need to change their behavior. The discrepancies described in this article are likely to apply to communications following any CBRNE disasters that affect people’s lives, such as the current COVID-19 pandemic. Therefore, our experiences in Fukushima may provide clues to averting mutual mistrust between experts and achieving better public health outcomes during and after a crisis.
Comprehensive analysis for detecting radiation-specific molecules expressed during radiation-induced rat thyroid carcinogenesis
Authors: Kurohama Hirokazu , Matsuda Katsuya , Kishino Mio , Yoshino Miruki , Yamaguchi Yuka , Matsuu-Matsuyama Mutsumi , Kondo Hisayoshi , Mitsutake Norisato , Kinoshita Akira , Yoshiura Ko-ichiro , Nakashima Masahiro
Published: December 2020

Although the association between radiation exposure and thyroid carcinogenesis is epidemiologically evident, ’true’ radiation-induced cancers cannot be identified from biological evidence of radiation-associated cases. To assess the individual risk for thyroid cancer due to radiation exposure, we aimed to identify biomarkers that are specifically altered during thyroid carcinogenesis after irradiation in a time-dependent manner in an animal model. Thyroid glands were obtained from rats (n = 175) at 6–16 months after local X-ray (0.1–4 Gy) irradiation of the neck at 7 weeks of age. The gene expression profile in thyroid glands was comprehensively analyzed using RNA microarray. Subsequently, the expression levels of the genes of interest were verified using droplet digital PCR (ddPCR). The expression level of candidate genes as biomarkers for irradiated thyroid was examined in a randomized, controlled, double-blind validation study (n = 19) using ddPCR. The incidence of thyroid cancer increased in a dose- and time-dependent manner and was 33% at 16 months after irradiation with 4 Gy. The Ki-67 labeling index in non-tumorous thyroid was significantly higher in the exposed group than in the control. Comprehensive analysis identified radiation-dependent alteration in 3329 genes. Among them, ddPCR revealed a stepwise increase in CDKN1A expression from early pre-cancerous phase in irradiated thyroid compared to that in the control. The irradiated thyroids were accurately distinguished (positive predictive value 100%, negative predictive value 69%) using 11.69 as the cut-off value for CDKN1A/β-actin. Thus, CDKN1A expression can be used as a biomarker for irradiated thyroid glands at the pre-cancerous phase.
Thoracoabdominal flap reconstruction after resection of superficial soft-tissue sarcomas in the chest wall
Authors: Sakamoto Akio , Noguchi Takashi , Matsuda Shuichi
Published: December 2020

The thoracoabdominal flap is a rotation flap, and is well known for reconstruction of defects following resections for breast cancer, but the flap is not well known for reconstructing defects following resections of soft-tissue sarcomas involving the chest wall. Here we present two patients with superficial chest wall sarcomas consisting of a dermatofibrosarcoma protuberans in a 42-year-old man and a recurrent myxofibrosarcoma in a 76-year-old man. The tumors were resected with the surrounding tissue. The defect was reconstructed with a thoracoabdominal flap elevated from the ipsilateral thorax (medially-based flap). Neither case developed necrosis of the flap or reduced shoulder range of motion. The chest wall presents few options for a donor vessel. The thoracoabdominal flap has an axial blood supply and does not require a microsurgical procedure. A thoracoabdominal flap is a suitable reconstruction option for a defect after the resection of a superficial soft-tissue sarcoma in the chest wall.
Temperature and evaporative demand drive variation in stomatal and hydraulic traits across grape cultivars
Authors: Bartlett Megan K , Sinclair Gabriela
Published: December 2020

Selection for crop cultivars has largely focused on reproductive traits, while the impacts of global change on crop productivity are expected to depend strongly on the vegetative physiology traits that drive plant resource use and stress tolerance. We evaluated relationships between physiology traits and growing season climate across wine grape cultivars to characterize trait variation across European growing regions. We compiled values from the literature for seven water use and drought tolerance traits and growing season climate. Cultivars with a lower maximum stomatal conductance were associated with regions with a higher mean temperature and mean and maximum vapor pressure deficit (r2=0.39–0.65, P<0.05, n=14–29). Cultivars with greater stem embolism resistance and more anisohydric stomatal behavior (i.e. a more negative water potential threshold for 50% stomatal closure) were associated with cooler regions (r2=0.48–0.72, P<0.03, n=10–29). Overall, cultivars grown in warmer, drier regions exhibited traits that would reduce transpiration and conserve soil water longer into the growing season, but potentially increase stomatal and temperature limitations on photosynthesis under future, hotter conditions.
Restriction of cytosolic sucrose hydrolysis profoundly alters development, metabolism, and gene expression in Arabidopsis roots
Authors: Pignocchi Cristina , Ivakov Alexander , Feil Regina , Trick Martin , Pike Marilyn , Wang Trevor L , Lunn John E , Smith Alison M
Published: December 2020

Plant roots depend on sucrose imported from leaves as the substrate for metabolism and growth. Sucrose and hexoses derived from it are also signalling molecules that modulate growth and development, but the importance for signalling of endogenous changes in sugar levels is poorly understood. We report that reduced activity of cytosolic invertase, which converts sucrose to hexoses, leads to pronounced metabolic, growth, and developmental defects in roots of Arabidopsis (Arabidopsis thaliana) seedlings. In addition to altered sugar and downstream metabolite levels, roots of cinv1 cinv2 mutants have reduced elongation rates, cell and meristem size, abnormal meristematic cell division patterns, and altered expression of thousands of genes of diverse functions. Provision of exogenous glucose to mutant roots repairs relatively few of the defects. The extensive transcriptional differences between mutant and wild-type roots have hallmarks of both high sucrose and low hexose signalling. We conclude that the mutant phenotype reflects both low carbon availability for metabolism and growth and complex sugar signals derived from elevated sucrose and depressed hexose levels in the cytosol of mutant roots. Such reciprocal changes in endogenous sucrose and hexose levels potentially provide rich information about sugar status that translates into flexible adjustments of growth and development.
Excitation of decayless kink oscillations by random motion
Authors: Ruderman M S , Petrukhin N S
Published: December 2020

We study kink oscillations of a straight magnetic tube with a transitional region at its boundary. The tube is homogeneous in the axial direction. The plasma density monotonically decreases in the transitional region from its value inside the tube to that in the surrounding plasma. The plasma motion is described by the linear magnetohydrodynamic equations in the cold plasma approximation. We use the ideal equations inside the tube and in the surrounding plasma, but take viscosity into account in the transitional region. We also use the thin tube and thin transitional or boundary layer (TTTB) approximation. Kink oscillations are assumed to be driven by a driver at the tube footpoint. We derive the equation describing the displacement in the fundamental mode and overtones. We use this equation to study kink oscillations both in the case of harmonic as well as random driving. In the case of random driving we assume that the driver is described by a stationary random function. The displacements in the fundamental mode and overtones are also described by stationary random functions. We derive the relation between the power spectra of the fundamental mode and all overtones and the power spectrum of the driver. We suggest a new method of obtaining information on the internal structure of coronal magnetic loops based on the shape of graphs of the power spectrum of the fundamental mode.
On the azimuthal alignment of quasars spin vector in large quasar groups and cosmic strings
Authors: Slagter Reinoud J , Miedema Pieter G
Published: December 2020

We find evidence of the alignment of the azimuthal angle of the spin vectors of quasars in their host galaxy in large quasar groups of different redshift. This effect could be explained by symmetry breaking of the scalar-gauge field of cosmic strings in the early universe. It is expected that this effect will be more profound for higher red shift.
Metformin: a novel promising option for fertility preservation during cyclophosphamide-based chemotherapy
Authors: Huang Chu-Chun , Chou Chia-Hung , Yang Yu-Shih , Ho Hong-Nerng , Shun Chia-Tung , Wen Wen-Fen , Chen Shee-Uan , Chen Mei-Jou
Published: December 2020

Cyclophosphamide (CP) could cause severe gonadotoxicity via imbalanced activation of primordial follicles through PI3K/AKT/mTOR activation. Whether metformin, a widely prescribed anti-diabetes agent with mTOR inhibitory effect, could preserve ovarian function against CP toxicity is unknown. Female C57BL/6 mice were randomized into seven groups (n = 11), including control, CP-alone, CP + metformin, CP + sirolimus or everolimus, metformin-alone and sirolimus-alone groups. The duration of pharmaceutical treatment was 4 weeks. CP treatment significantly impaired ovarian function and fertility in mice. CP + metformin treatment significantly attenuated the gonadotoxicity comparing to CP-alone treatment (primordial follicle count: 17.6 ± 4.2 versus 10.3 ± 2.7 follicles/high-power field; P = 0.027). CP + metformin treatment also tended to increase antral follicular count (5.4 ± 1.1 versus 2.5 ± 1.6 follicles/section), serum AMH levels (4.6 ± 1.2 versus 2.0 ± 0.8 ng/ml) and the litter size (4.2 ± 1.3 versus 1.5 ± 1.0 mice per pregnancy), compared with CP-alone group. Expression of phospho-mTOR and the number of TUNEL-positive granulosa cells increased after CP treatment and decreased in the CP + metformin groups, suggesting the mTOR inhibitory and anti-apoptotic effects of metformin. In in-vitro granulosa cell experiments, the anti-apoptotic effect of metformin was blocked after inhibiting p53 or p21 function, and the expression of p53 mRNA was blocked with AMPK inhibitor, suggesting that the anti-apoptotic effect was AMPK/p53/p21-mediated. In conclusion, concurrent metformin treatment during CP therapy could significantly preserve ovarian function and fertility and could be a promising novel fertility preserving agent during chemotherapy. The relatively acceptable cost and well-established long-term safety profiles of this old drug might prompt its further clinical application at a faster pace.
Identification of lysine isobutyrylation as a new histone modification mark
Authors: Zhu Zhesi , Han Zhen , Halabelian Levon , Yang Xiangkun , Ding Jun , Zhang Nawei , Ngo Liza , Song Jiabao , Zeng Hong , He Maomao , Zhao Yingming , Arrowsmith Cheryl H , Luo Minkui , Bartlett Michael G , Zheng Y George
Published: December 2020

Short-chain acylations of lysine residues in eukaryotic proteins are recognized as essential posttranslational chemical modifications (PTMs) that regulate cellular processes from transcription, cell cycle, metabolism, to signal transduction. Lysine butyrylation was initially discovered as a normal straight chain butyrylation (Knbu). Here we report its structural isomer, branched chain butyrylation, i.e. lysine isobutyrylation (Kibu), existing as a new PTM on nuclear histones. Uniquely, isobutyryl-CoA is derived from valine catabolism and branched chain fatty acid oxidation which is distinct from the metabolism of n-butyryl-CoA. Several histone acetyltransferases were found to possess lysine isobutyryltransferase activity in vitro, especially p300 and HAT1. Transfection and western blot experiments showed that p300 regulated histone isobutyrylation levels in the cell. We resolved the X-ray crystal structures of HAT1 in complex with isobutyryl-CoA that gleaned an atomic level insight into HAT-catalyzed isobutyrylation. RNA-Seq profiling revealed that isobutyrate greatly affected the expression of genes associated with many pivotal biological pathways. Together, our findings identify Kibu as a novel chemical modification mark in histones and suggest its extensive role in regulating epigenetics and cellular physiology.
In vitroselections with RNAs of variable length converge on a robust catalytic core
Authors: Popović Milena , Ellingson Alexander Q , Chu Theresa P , Wei Chenyu , Pohorille Andrew , Ditzler Mark A
Published: December 2020

In vitro selection is a powerful tool that can be used to understand basic principles of molecular evolution. We used in vitro selection to understand how changes in length and the accumulation of point mutations enable the evolution of functional RNAs. Using RNA populations of various lengths, we performed a series of in vitro experiments to select for ribozymes with RNA ligase activity. We identified a core ribozyme structure that was robust to changes in RNA length, high levels of mutagenesis, and increased selection pressure. Elaboration on this core structure resulted in improved activity which we show is consistent with a larger trend among functional RNAs in which increasing motif size can lead to an exponential improvement in fitness. We conclude that elaboration on conserved core structures is a preferred mechanism in RNA evolution. This conclusion, drawn from selections of RNAs from random sequences, is consistent with proposed evolutionary histories of specific biological RNAs. More generally, our results indicate that modern RNA structures can be used to infer ancestral structures. Our observations also suggest a mechanism by which structural outcomes of early RNA evolution would be largely reproducible even though RNA fitness landscapes consist of disconnected clusters of functional sequences.
Catalytically inactive Cas9 impairs DNA replication fork progression to induce focal genomic instability
Authors: Doi Goro , Okada Satoshi , Yasukawa Takehiro , Sugiyama Yuki , Bala Siqin , Miyazaki Shintaro , Kang Dongchon , Ito Takashi
Published: December 2020

Catalytically inactive Cas9 (dCas9) has become an increasingly popular tool for targeted gene activation/inactivation, live-cell imaging, and base editing. While dCas9 was reported to induce base substitutions and indels, it has not been associated with structural variations. Here, we show that dCas9 impedes replication fork progression to destabilize tandem repeats in budding yeast. When targeted to the CUP1 array comprising ∼16 repeat units, dCas9 induced its contraction in most cells, especially in the presence of nicotinamide. Replication intermediate analysis demonstrated replication fork stalling in the vicinity of dCas9-bound sites. Genetic analysis indicated that while destabilization is counteracted by the replisome progression complex components Ctf4 and Mrc1 and the accessory helicase Rrm3, it involves single-strand annealing by the recombination proteins Rad52 and Rad59. Although dCas9-mediated replication fork stalling is a potential risk in conventional applications, it may serve as a novel tool for both mechanistic studies and manipulation of genomic instability.
Circulating angiopoietin-2 and angiogenic microRNAs associate with cerebral small vessel disease and cognitive decline in older patients reaching end-stage renal disease
Authors: Bijkerk Roel , Kallenberg Marije H , Zijlstra Laurien E , van den Berg Bernard M , de Bresser Jeroen , Hammer Sebastiaan , Bron Esther E , Achterberg Hakim , van Buchem Mark A , Berkhout-Byrne Noeleen C , Bos Willem Jan W , van Heemst Diana , Rabelink Ton J , van Zonneveld Anton Jan , van Buren Marjolijn , Mooijaart Simon
Published: December 2020

Background

The prevalence of end-stage renal disease (ESRD) is increasing worldwide, with the majority of new ESRD cases diagnosed in patients >60 years of age. These older patients are at increased risk for impaired cognitive functioning, potentially through cerebral small vessel disease (SVD). Novel markers of vascular integrity may be of clinical value for identifying patients at high risk for cognitive impairment.

Methods

We aimed to associate the levels of angiopoietin-2 (Ang-2), asymmetric dimethylarginine and a selection of eight circulating angiogenic microRNAs (miRNAs) with SVD and cognitive impairment in older patients reaching ESRD that did not yet initiate renal replacement therapy (n = 129; mean age 75.3 years, mean eGFR 16.4 mL/min). We assessed brain magnetic resonance imaging changes of SVD (white matter hyperintensity volume, microbleeds and the presence of lacunes) and measures of cognition in domains of memory, psychomotor speed and executive function in a neuropsychological test battery.

Results

Older patients reaching ESRD showed an unfavourable angiogenic profile, as indicated by aberrant levels of Ang-2 and five angiogenic miRNAs (miR-27a, miR-126, miR-132, miR-223 and miR-326), compared with healthy persons and patients with diabetic nephropathy. Moreover, Ang-2 was associated with SVD and with the domains of psychomotor speed and executive function, while miR-223 and miR-29a were associated with memory function.

Conclusions

Taken together, these novel angiogenic markers might serve to identify older patients with ESRD at risk of cognitive decline, as well as provide insights into the underlying (vascular) pathophysiology.
Comprehensive Nutrient Gap Assessment (CONGA): A method for identifying the public health significance of nutrient gaps
Authors: Beal Ty , White Jessica M , Arsenault Joanne E , Okronipa Harriet , Hinnouho Guy-Marino , Morris Saul S
Published: December 2020

Identifying dietary nutrient gaps and interpreting their public health significance are essential for improving poor diets and reducing malnutrition. Evidence indicative of the burden of nutrient deficiencies and inadequate nutrient intake or availability exists in many countries yet is often misinterpreted or underused in decision-making. Clear guidance is lacking on how to synthesize and interpret the relevant evidence, which comes in many forms. To fill this methodological gap, an approach called Comprehensive Nutrient Gap Assessment was created to enable use of existing evidence to assess the public health significance of nutrient gaps and identify evidence gaps. Comprehensive Nutrient Gap Assessment requires ≥ 2 experts in nutritional assessment but does not require primary data collection or secondary quantitative data analysis. It can be implemented relatively quickly with low costs, for specific countries and subnational regions, and updated on the basis of new data with minimal effort. The findings from a Comprehensive Nutrient Gap Assessment are easily interpretable by nontechnical decision makers yet include clear justification for technical audiences.
Pressurized Liquid Extraction of a Phycocyanobilin Chromophore and Its Reconstitution with a Cyanobacteriochrome Photosensor for Efficient Isotopic Labeling
Authors: Kamo Takanari , Eki Toshihiko , Hirose Yuu
Published: December 2020

Linear tetrapyrrole compounds (bilins) are chromophores of the phytochrome and cyanobacteriochrome classes of photosensors and light-harvesting phycobiliproteins. Various spectroscopic techniques, such as resonance Raman, Fourier transform-infrared and nuclear magnetic resonance, have been used to elucidate the structures underlying their remarkable spectral diversity, in which the signals are experimentally assigned to specific structures using isotopically labeled bilin. However, current methods for isotopic labeling of bilins require specialized expertise, time-consuming procedures and/or expensive reagents. To address these shortcomings, we established a method for pressurized liquid extraction of phycocyanobilin (PCB) from the phycobiliprotein powder Lina Blue and also the cyanobacterium Synechocystis sp. PCC 6803 (Synechocystis). PCB was efficiently cleaved in ethanol with three extractions (5 min each) under nitrogen at 125�C and 100 bars. A prewash at 75�C was effective for removing cellular pigments of Synechocystis without PCB cleavage. Liquid chromatography and mass spectrometry suggested that PCB was cleaved in the C3-E (majority) and C3-Z (partial) configurations. 15N- and 13C/15N-labeled PCBs were prepared from Synechocystis cells grown with NaH13CO3 and/or Na15NO3, the concentrations of which were optimized based on cell growth and pigmentation. Extracted PCB was reconstituted with a recombinant apoprotein of the cyanobacteriochrome-class photosensor RcaE. Yield of the photoactive holoprotein was improved by optimization of the expression conditions and cell disruption in the presence of Tween 20. Our method can be applied for the isotopic labeling of other PCB-binding proteins and for the commercial production of non-labeled PCB for food, cosmetic and medical applications.
A continuation method for building invisible obstacles in waveguides
Authors: Bera Antoine , Bonnet-Ben Dhia Anne-Sophie , Chesnel Lucas
Published: December 2020

We consider the propagation of acoustic waves in a waveguide which is unbounded in one direction. We explain how to construct at a given wavenumber penetrable obstacles characterised by a physical coefficient $\rho$ which are invisible in various ways. In particular, we focus our attention on invisibility in reflection (the reflection matrix is zero), invisibility in reflection and transmission (the scattering matrix is the same as if there were no obstacle) and relative invisibility (two different obstacles have the same scattering matrix). To study these problems, we use a continuation method which requires to compute the scattering matrix $\mathbb{S}(\rho)$ as well as its differential with respect to the material index $d\mathbb{S}(\rho)$. The justification of the method also needs for the proof of abstract results of surjectivity of well-chosen functionals constructed from the terms of $d\mathbb{S}(\rho)$. We provide a complete proof of the results in monomode regime when the wavenumber is such that only one mode can propagate. And we give all the ingredients to implement the method in multimode regime. We end the article by presenting numerical results to illustrate the analysis.
Autonomic dysregulation and sleep homeostasis in insomnia
Authors: Grimaldi Daniela , Reid Kathryn J , Papalambros Nelly A , Braun Rosemary I , Malkani Roneil G , Abbott Sabra M , Ong Jason C , Zee Phyllis C
Published: December 2020

Study Objectives

Insomnia is common in older adults, and is associated with poor health, including cognitive impairment and cardio-metabolic disease. Although the mechanisms linking insomnia with these comorbidities remain unclear, age-related changes in sleep and autonomic nervous system (ANS) regulation might represent a shared mechanistic pathway. In this study, we assessed the relationship between ANS activity with indices of objective and subjective sleep quality in older adults with insomnia.

Methods

Forty-three adults with chronic insomnia and 16 age-matched healthy sleeper controls were studied. Subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), objective sleep quality by electroencephalogram spectral components derived from polysomnography, and ANS activity by measuring 24-h plasma cortisol and norepinephrine (NE).

Results

Sleep cycle analysis displayed lower slow oscillatory (SO: 0.5–1.25 Hz) activity in the first cycle in insomnia compared to controls. In insomnia, 24-h cortisol levels were higher and 24-h NE levels were lower than controls. In controls, but not in insomnia, there was a significant interaction between NE level during wake and SO activity levels across the sleep cycles, such that in controls but not in insomnia, NE level during wake was positively associated with the amount of SO activity in the first cycle. In insomnia, lower 24-h NE level and SO activity in the first sleep cycle were associated with poorer subjective sleep quality.

Conclusion

Dysregulation of autonomic activity may be an underlying mechanism that links objective and subjective measures of sleep quality in older adults with insomnia, and potentially contribute to adverse health outcomes.
The Nordic Model of Father Quotas in Leave Policies: A Case of Policy Transfer?
Authors: Windwehr Jana , Duvander Ann-Zofie , Ellingsæter Anne Lise , Eydal Guðný Björk , Humer Živa , Nakazato Hideki
Published: December 2020

This contribution asks whether the most recent innovation of Nordic family policies, the so-called father quota, has been an object of policy learning in countries that followed the Nordic example of leave policies earlier, such as Germany, Slovenia, and Japan. Our case studies show that analyses of policy learning, especially in the social field, need to take into account the specific contexts and actor constellations in “export” and “import” countries. Rather than representing a blueprint, the Nordic father quotas have served as an inspiration within messy and fragmented processes of policy learning leading to hybrid arrangements in import countries.
The impact of international sanctions on Jersey trust structures
Authors: Wickham Henry
Published: December 2020

Sanctions issued by the United Nations, USA and European Union are at the top of the risk agenda, particularly for financial institutions. This trend is set to be continued by the post-Brexit UK following its passing of the Sanctions and Anti-Money Laundering Act 2018 which, among other things, enables the UK to enact its own autonomous sanctions. Consistent with its commitment to meeting international standards, Jersey has a legal framework which supports the implementation of such sanctions.