bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of asymptomatic carotid stenosis in patients with lower-extremity arterial disease: development and external validations of a risk score
Authors: Poorthuis M H F , Morris D R , de Borst G J , Bots M L , Greving J P , Visseren F L J , Sherliker P , Clack R , Clarke R , Lewington S , Bulbulia R , Halliday A
Published: January 2021

Background

Recommendations for screening patients with lower-extremity arterial disease (LEAD) to detect asymptomatic carotid stenosis (ACS) are conflicting. Prediction models might identify patients at high risk of ACS, possibly allowing targeted screening to improve preventive therapy and compliance.

Methods

A systematic search for prediction models for at least 50 per cent ACS in patients with LEAD was conducted. A prediction model in screened patients from the USA with an ankle : brachial pressure index of 0.9 or less was subsequently developed, and assessed for discrimination and calibration. External validation was performed in two independent cohorts, from the UK and the Netherlands.

Results

After screening 4907 studies, no previously published prediction models were found. For development of a new model, data for 112 117 patients were used, of whom 6354 (5.7 per cent) had at least 50 per cent ACS and 2801 (2.5 per cent) had at least 70 per cent ACS. Age, sex, smoking status, history of hypercholesterolaemia, stroke/transient ischaemic attack, coronary heart disease and measured systolic BP were predictors of ACS. The model discrimination had an area under the receiver operating characteristic (AUROC) curve of 0.71 (95 per cent c.i. 0.71 to 0.72) for at least 50 per cent ACS and 0.73 (0.72 to 0.73) for at least 70 per cent ACS. Screening the 20 per cent of patients at greatest risk detected 12.4 per cent with at least 50 per cent ACS (number needed to screen (NNS) 8] and 5.8 per cent with at least 70 per cent ACS (NNS 17). This yielded 44.2 and 46.9 per cent of patients with at least 50 and 70 per cent ACS respectively. External validation showed reliable discrimination and adequate calibration.

Conclusion

The present risk score can predict significant ACS in patients with LEAD. This approach may inform targeted screening of high-risk individuals to enhance the detection of ACS.
An update on the role of anti-IL-12/IL23 agents in the management of inflammatory bowel disease
Authors: Nigam Gaurav B , Limdi Jimmy K
Published: January 2021

Introduction

The aim of treatment in inflammatory bowel disease (IBD) is to control symptoms and suppress gut inflammation with minimal systemic side effects. A large proportion of patients are either primary non-responders or lose response to currently licensed therapies. The development of monoclonal antibodies, blocking interleukin (IL)-12 and IL-23 pathways are a promising therapeutic advance. We review the data on IL12/23 inhibitors and emerging data on IL-23 inhibition in IBD treatment.

Sources of data

This review is based on data published in peer-reviewed journals and clinical trials registry.

Areas of agreement

Ustekinumab is currently approved for managing corticosteroid and biologic refractory IBD patients with a favourable safety profile.

Areas of controversy

Despite a growing therapeutic armamentarium and convergence on the role of biological therapies in patients with greater disease severity, there remains considerable uncertainty with selection and positioning of treatment.

Growing points

Efficacy data from clinical trials and a growing body of real-world data have established a role for IL12/23 inhibitor Ustekinumab in IBD. There is resurgent interest in IL-23 specificity and the potential for incremental benefit. The potential for IL-22 to act as a biomarker for IL-23 inhibitors has exciting implications for personalized medicine.

Areas timely for developing research

Head-to-head trials exploring efficacy and combination with other biologics with the potential for synergistic benefit are under investigation. Results of phase 3 trials with IL-23 inhibitors incorporating clinical, biochemical and endoscopic parameters and also exploring biomarkers as predictors of response are urgently needed.
Evidence that autosomal recessive spastic cerebral palsy-1 (CPSQ1) is caused by a missense variant in HPDL
Authors: Morgan Neil V , Yngvadottir Bryndis , O’Driscoll Mary , Clark Graeme R , Walsh Diana , Martin Ezequiel , Tee Louise , Reid Evan , Titheradge Hannah L , Maher Eamonn R
Published: January 2021

A subset of individuals diagnosed with cerebral palsy will have an underlying genetic diagnosis. Previously, a missense variant in GAD1 was described as a candidate mutation in a single family diagnosed with autosomal recessive spastic cerebral palsy-1 (CPSQ1; OMIM 603513). Following the ascertainment of a further branch of the CPSQ1 kindred, we found that the previously reported GAD1 variant did not segregate with the neurological disease phenotype in the recently ascertained branch of the kindred. Following genetic linkage studies to map autozygous regions and whole-exome sequencing, a missense variant (c.527 T > C; p. Leu176Pro, rs773333490) in the HPDL gene was detected and found to segregate with disease status in both branches of the kindred. HPDL encodes a 371-amino acid protein (4-Hydroxyphenylpyruvate Dioxygenase Like) that localizes to mitochondria but whose function is uncertain. Recently, biallelic loss of function variants and missense substitution-causing variants in HPDL were reported to cause a childhood onset progressive spastic movement disorder with a variable presentation. These findings suggest that HPDL-related neurological disease may mimic spastic cerebral palsy and that GAD1 should not be included in diagnostic gene panels for inherited cerebral palsy.
Brain Gene Expression Pattern Correlated with the Differential Brain Activation by Pain and Touch in Humans
Authors: Tang Jie , Su Qian , Zhang Xue , Qin Wen , Liu Huaigui , Liang Meng , Yu Chunshui
Published: January 2021

Genes involved in pain and touch sensations have been studied extensively, but very few studies have tried to link them with neural activities in the brain. Here, we aimed to identify genes preferentially correlated to painful activation patterns by linking the spatial patterns of gene expression of Allen Human Brain Atlas with the pain-elicited neural responses in the human brain, with a parallel, control analysis for identification of genes preferentially correlated to tactile activation patterns. We identified 1828 genes whose expression patterns preferentially correlated to painful activation patterns and 411 genes whose expression patterns preferentially correlated to tactile activation pattern at the cortical level. In contrast to the enrichment for astrocyte and inhibitory synaptic transmission of genes preferentially correlated to tactile activation, the genes preferentially correlated to painful activation were mainly enriched for neuron and opioid- and addiction-related pathways and showed significant overlap with pain-related genes identified in previous studies. These findings not only provide important evidence for the differential genetic architectures of specific brain activation patterns elicited by painful and tactile stimuli but also validate a new approach to studying pain- and touch-related genes more directly from the perspective of neural responses in the human brain.
Spatial concentration of manufacturing industries in the United States: re-examination of long-run trends
Authors: Crafts Nicholas , Klein Alexander
Published: January 2021

We re-examine the long-run geographical development of US manufacturing industries using recent advances in spatial concentration measures. We construct spatially weighted indices of the geographical concentration between 1880 and 2007 taking into account industrial structure and checkerboard problem. New results emerge. Average spatial concentration was much lower in the late 20th than in the late 19th century, and it was the outcome of a continuing reduction over time. Spatial concentration did not increase in the early 20th century but declined, and we find no inverted-U shape pattern of long-run spatial concentration. The persistent tendency to greater spatial dispersion was characteristic of most industries.
Lipoprotein(a) is associated with large artery atherosclerosis stroke aetiology and stroke recurrence among patients below the age of 60 years: results from the BIOSIGNAL study
Authors: Arnold Markus , Schweizer Juliane , Nakas Christos T , Schütz Valerie , Westphal Laura P , Inauen Corinne , Pokorny Thomas , Luft Andreas , Leichtle Alexander , Arnold Marcel , Bicvic Antonela , Fischer Urs , De Marchis Gian Marco , Bonati Leo H , Müller Mandy D , Kahles Timo , Nedeltchev Krassen , Cereda Carlo W , Kägi Georg , Bustamante Alejandro , Montaner Joan , Ntaios George , Foerch Christian , Spanaus Katharina , von Eckardstein Arnold , Katan Mira
Published: January 2021

Aims

Lipoprotein(a) [Lp(a)] is a recognized causal risk factor for atherosclerotic cardiovascular disease but its role for acute ischaemic stroke (AIS) is controversial. In this study, we evaluated the association of Lp(a) with large artery atherosclerosis (LAA) stroke and risk of recurrent cerebrovascular events in AIS patients.

Methods and results

For this analysis of the prospective, observational, multicentre BIOSIGNAL cohort study we measured Lp(a) levels in plasma samples of 1733 primarily Caucasian (98.6%) AIS patients, collected within 24 h after symptom onset. Primary outcomes were LAA stroke aetiology and recurrent cerebrovascular events (ischaemic stroke or transient ischaemic attack) within 1 year. We showed that Lp(a) levels are independently associated with LAA stroke aetiology [adjusted odds ratio 1.48, 95% confidence interval (CI) 1.14-1.90, per unit log10Lp(a) increase] and identified age as a potent effect modifier (Pinteraction =0.031) of this association. The adjusted odds ratio for LAA stroke in patients aged <60 years was 3.64 (95% CI 1.76–7.52) per unit log10Lp(a) increase and 4.04 (95% CI 1.73–9.43) using the established cut-off ≥100 nmol/l. For 152 recurrent cerebrovascular events, we did not find a significant association in the whole cohort. However, Lp(a) levels ≥100 nmol/l were associated with an increased risk for recurrent events among patients who were either <60 years [adjusted hazard ratio (HR) 2.40, 95% CI 1.05–5.47], had evident LAA stroke aetiology (adjusted HR 2.18, 95% CI 1.08–4.40), or had no known atrial fibrillation (adjusted HR 1.60, 95% CI 1.03–2.48).

Conclusion

Elevated Lp(a) was independently associated with LAA stroke aetiology and risk of recurrent cerebrovascular events among primarily Caucasian individuals aged <60 years or with evident arteriosclerotic disease.
Individual Tree and Stand Level Influences on the Growth, Vigor, and Decline of Red Oaks in the Ozarks
Authors: Voelker Steven L. , Muzika Rose-Marie , Guyette Richard P.
Published: January 2021

Repeated oak decline and mortality events have occurred in the Ozark region for decades and probably longer. We sampled an age sequence of 1,259 black and scarlet oaks (Quercus velutina Lam. and Quercus coccinea Muench.) to better describe the process of oak decline and mortality in the red oak group (subgenera Erythrobalanus). Trend in basal area increment (BAI) over the most recent 40 years was used to establish three vigor classes for trees with decreasing, stable, or increasing growth (Declining, Stable, or Healthy). We compared crown condition measures with absolute BAI and boundary line BAI, a measure of radial growth adjusted for tree size. A pulse of mortality was found to occur just subsequent to the most recent drought, although decline often started decades previously. Time series of individual tree BAI suggests that half of all oak decline events were incited by one or two drought-related step-changes in growth and variance. Predisposing factors to decline generally showed significant but weak relationships with crown conditions. Surviving oaks growing in high-mortality stands had poorer crown conditions and grew more slowly than trees in low-mortality stands. When recently dead trees were accounted for, the same high-mortality stands had significantly greater predecline basal area and stocking than low-mortality stands. Thus, a less competitive growth environment may afford some buffer to drought stress before oak decline but does not appear to help afflicted stands improve their growth and vigor.
A cohort ofCaenorhabditisspecies lacking the highly conservedlet-7microRNA
Authors: Nelson Charles , Ambros Victor
Published: January 2021

The let-7 gene encodes a highly conserved microRNA with critical functions integral to cell fate specification and developmental progression in diverse animals. In Caenorhabditis elegans, let-7 is a component of the heterochronic (developmental timing) gene regulatory network, and loss-of-function mutations of let-7 result in lethality during the larval to adult transition due to misregulation of the conserved let-7 target, lin-41. To date, no bilaterian animal lacking let-7 has been characterized. In this study, we identify a cohort of nematode species within the genus Caenorhabditis, closely related to C. elegans, that lack the let-7 microRNA, owing to absence of the let-7 gene. Using Caenorhabditis sulstoni as a representative let-7-lacking species to characterize normal larval development in the absence of let-7, we demonstrate that, except for the lack of let-7, the heterochronic gene network is otherwise functionally conserved. We also report that species lacking let-7 contain a group of divergent let-7 paralogs—also known as the let-7-family of microRNAs—that have apparently assumed the role of targeting the LIN-41 mRNA.
The fission yeast S-phase cyclin Cig2 can drive mitosis
Authors: Pickering Mary , Magner Mira , Keifenheim Dan , Rhind Nicholas
Published: January 2021

Commitment to mitosis is regulated by cyclin-dependent kinase (CDK) activity. In the fission yeast Schizosaccharomyces pombe, the major B-type cyclin, Cdc13, is necessary and sufficient to drive mitotic entry. Furthermore, Cdc13 is also sufficient to drive S phase, demonstrating that a single cyclin can regulate alternating rounds of replication and mitosis, and providing the foundation of the quantitative model of CDK function. It has been assumed that Cig2, a B-type cyclin expressed only during S phase and incapable of driving mitosis in wild-type cells, was specialized for S-phase regulation. Here, we show that Cig2 is capable of driving mitosis. Cig2/CDK activity drives mitotic catastrophe—lethal mitosis in inviably small cells—in cells that lack CDK inhibition by tyrosine-phosphorylation. Moreover, Cig2/CDK can drive mitosis in the absence of Cdc13/CDK activity and constitutive expression of Cig2 can rescue loss of Cdc13 activity. These results demonstrate that in fission yeast, not only can the presumptive M-phase cyclin drive S phase, but the presumptive S-phase cyclin can drive M phase, further supporting the quantitative model of CDK function. Furthermore, these results provide an explanation, previously proposed on the basis of computational analyses, for the surprising observation that cells expressing a single-chain Cdc13-Cdc2 CDK do not require Y15 phosphorylation for viability. Their viability is due to the fact that in such cells, which lack Cig2/CDK complexes, Cdc13/CDK activity is unable to drive mitotic catastrophe.
Assessing the regulatory potential of transposable elements using chromatin accessibility profiles of maize transposons
Authors: Noshay Jaclyn M , Marand Alexandre P , Anderson Sarah N , Zhou Peng , Mejia Guerra Maria Katherine , Lu Zefu , O’Connor Christine H , Crisp Peter A , Hirsch Candice N , Schmitz Robert J , Springer Nathan M
Published: January 2021

Transposable elements (TEs) have the potential to create regulatory variation both through the disruption of existing DNA regulatory elements and through the creation of novel DNA regulatory elements. In a species with a large genome, such as maize, many TEs interspersed with genes create opportunities for significant allelic variation due to TE presence/absence polymorphisms among individuals. We used information on putative regulatory elements in combination with knowledge about TE polymorphisms in maize to identify TE insertions that interrupt existing accessible chromatin regions (ACRs) in B73 as well as examples of polymorphic TEs that contain ACRs among four inbred lines of maize including B73, Mo17, W22, and PH207. The TE insertions in three other assembled maize genomes (Mo17, W22, or PH207) that interrupt ACRs that are present in the B73 genome can trigger changes to the chromatin, suggesting the potential for both genetic and epigenetic influences of these insertions. Nearly 20% of the ACRs located over 2 kb from the nearest gene are located within an annotated TE. These are regions of unmethylated DNA that show evidence for functional importance similar to ACRs that are not present within TEs. Using a large panel of maize genotypes, we tested if there is an association between the presence of TE insertions that interrupt, or carry, an ACR and the expression of nearby genes. While most TE polymorphisms are not associated with expression for nearby genes, the TEs that carry ACRs exhibit enrichment for being associated with higher expression of nearby genes, suggesting that these TEs may contribute novel regulatory elements. These analyses highlight the potential for a subset of TEs to rewire transcriptional responses in eukaryotic genomes.
Evaluating human autosomal loci for sexually antagonistic viability selection in two large biobanks
Authors: Kasimatis Katja R , Abraham Abin , Ralph Peter L , Kern Andrew D , Capra John A , Phillips Patrick C
Published: January 2021

Sex and sexual differentiation are pervasive across the tree of life. Because females and males often have substantially different functional requirements, we expect selection to differ between the sexes. Recent studies in diverse species, including humans, suggest that sexually antagonistic viability selection creates allele frequency differences between the sexes at many different loci. However, theory and population-level simulations indicate that sex-specific differences in viability would need to be very large to produce and maintain reported levels of between-sex allelic differentiation. We address this contradiction between theoretical predictions and empirical observations by evaluating evidence for sexually antagonistic viability selection on autosomal loci in humans using the largest cohort to date (UK Biobank, n = 487,999) along with a second large, independent cohort (BioVU, n = 93,864). We performed association tests between genetically ascertained sex and autosomal loci. Although we found dozens of genome-wide significant associations, none replicated across cohorts. Moreover, closer inspection revealed that all associations are likely due to cross-hybridization with sex chromosome regions during genotyping. We report loci with potential for mis-hybridization found on commonly used genotyping platforms that should be carefully considered in future genetic studies of sex-specific differences. Despite being well powered to detect allele frequency differences of up to 0.8% between the sexes, we do not detect clear evidence for this signature of sexually antagonistic viability selection on autosomal variation. These findings suggest a lack of strong ongoing sexually antagonistic viability selection acting on single locus autosomal variation in humans.
Protein quality control degron-containing substrates are differentially targeted in the cytoplasm and nucleus by ubiquitin ligases
Authors: Hickey Christopher M , Breckel Carolyn , Zhang Mengwen , Theune William C , Hochstrasser Mark
Published: January 2021

Intracellular proteolysis by the ubiquitin–proteasome system regulates numerous processes and contributes to protein quality control (PQC) in all eukaryotes. Covalent attachment of ubiquitin to other proteins is specified by the many ubiquitin ligases (E3s) expressed in cells. Here we determine the E3s in Saccharomyces cerevisiae that function in degradation of proteins bearing various PQC degradation signals (degrons). The E3 Ubr1 can function redundantly with several E3s, including nuclear-localized San1, endoplasmic reticulum/nuclear membrane-embedded Doa10, and chromatin-associated Slx5/Slx8. Notably, multiple degrons are targeted by more ubiquitylation pathways if directed to the nucleus. Degrons initially assigned as exclusive substrates of Doa10 were targeted by Doa10, San1, and Ubr1 when directed to the nucleus. By contrast, very short hydrophobic degrons—typical targets of San1—are shown here to be targeted by Ubr1 and/or San1, but not Doa10. Thus, distinct types of PQC substrates are differentially recognized by the ubiquitin system in a compartment-specific manner. In human cells, a representative short hydrophobic degron appended to the C-terminus of GFP-reduced protein levels compared with GFP alone, consistent with a recent study that found numerous natural hydrophobic C-termini of human proteins can act as degrons. We also report results of bioinformatic analyses of potential human C-terminal degrons, which reveal that most peptide substrates of Cullin-RING ligases (CRLs) are of low hydrophobicity, consistent with previous data showing CRLs target degrons with specific sequences. These studies expand our understanding of PQC in yeast and human cells, including the distinct but overlapping PQC E3 substrate specificity of the cytoplasm and nucleus.
Health and Subjective Views on Aging: Longitudinal Findings From the ActiFE Ulm Study
Authors: Schönstein Anton , Dallmeier Dhayana , Denkinger Michael , Rothenbacher Dietrich , Klenk Jochen , Bahrmann Anke , Wahl Hans-Werner
Published: January 2021

Objectives

Previous research supports that subjective views on aging (VoA), such as older subjective age (SA) and negative attitudes toward own aging (ATOA), go along with negative outcomes. A differentiated treatment of health and disease as antecedents of VoA is largely lacking. Therefore, our objective was to estimate the relationship between generally framed physical, affective, and cognitive health as well as specific diseases and VoA, operationalized both as SA and ATOA.

Methods

Data were drawn from the ActiFE Ulm study for which a representative sample of community-dwelling older people (65–90 years) was recruited at baseline. Follow-ups were conducted 7.7 years (median) after recruitment (N = 526). Health- and disease-related data at baseline, based on established assessment procedures for epidemiological studies, were regressed on VoA (1-item SA indicator, 5-item ATOA scale) measures at follow-up.

Results

Reported severity of affective health problems such as depression was the strongest general risk factor for both older SA and negative ATOA. Also, some but not all major diseases considered were associated with VoA. Notably, back pain predicted negative ATOA, while cancer was associated with older SA. Rheumatism was linked with more negative ATOA along with higher SA. Throughout analyses, explained variance in ATOA was considerably higher than in SA.

Discussion

Affective health problems, such as depression, should be regarded as a major correlate of subjective aging views. Interestingly, diseases do not have to be life-threatening to be associated with older SA or negative ATOA.
The Formal Shift Operator on the Yangian Double
Authors: Wendlandt Curtis
Published: January 2021

Let ${\mathfrak{g}}$ be a symmetrizable Kac–Moody algebra with associated Yangian $Y_\hbar{\mathfrak{g}}$ and Yangian double $\textrm{D}Y_\hbar{\mathfrak{g}}$. An elementary result of fundamental importance to the theory of Yangians is that, for each $c\in{\mathbb{C}}$, there is an automorphism $\tau _c$ of $Y_\hbar{\mathfrak{g}}$ corresponding to the translation $t\mapsto t+c$ of the complex plane. Replacing $c$ by a formal parameter $z$ yields the so-called formal shift homomorphism $\tau _z$ from $Y_\hbar{\mathfrak{g}}$ to the polynomial algebra $Y_\hbar{\mathfrak{g}}[z]$. We prove that $\tau _z$ uniquely extends to an algebra homomorphism $\Phi _z$ from the Yangian double $\textrm{D}Y_\hbar{\mathfrak{g}}$ into the $\hbar $-adic closure of the algebra of Laurent series in $z^{-1}$ with coefficients in the Yangian $Y_\hbar{\mathfrak{g}}$. This induces, via evaluation at any point $c\in{\mathbb{C}}^\times $, a homomorphism from $\textrm{D}Y_\hbar{\mathfrak{g}}$ into the completion of the Yangian with respect to its grading. We show that each such homomorphism gives rise to an isomorphism between completions of $\textrm{D}Y_\hbar{\mathfrak{g}}$ and $Y_\hbar{\mathfrak{g}}$ and, as a corollary, we find that the Yangian $Y_\hbar{\mathfrak{g}}$ can be realized as a degeneration of the Yangian double $\textrm{D}Y_\hbar{\mathfrak{g}}$. Using these results, we obtain a Poincaré–Birkhoff–Witt theorem for $\textrm{D}Y_\hbar{\mathfrak{g}}$ applicable when ${\mathfrak{g}}$ is of finite type or of simply laced affine type.
Sufi Reformism and the Politics of Enchantment in Nasser’s Egypt (1954–1970)
Authors: Zárate Arthur Shiwa
Published: January 2021

Although theories of disenchantment have been both utilized and critiqued by scholars of Islam, they have not received sufficient critical scrutiny within historical studies on Islamic reformism, a novel religiosity associated with modernity’s emergence in Muslim societies. Indeed, histories of Islamic reformism often portray this novel religiosity as an exclusive force of disenchantment, which is unhelpful for understanding the views of Muslims with reformist commitments and attachments to Sufi practices that invest supernatural powers into bodies and objects. Through an analysis of the Sufi Islamic reformist project of the ʿAshira Muhammadiyya organization in Egypt during the Nasser years (1954–1970), this article highlights how the history of Islamic reformism resonates with and diverges from disenchantment theories. Specifically, it foregrounds the way this Sufi reformism not only framed its objectives in terms of progress, science, and socialism but also presumed a reformist Sufi subject constituted through encounters with unseen supernatural agents.
Regulation of lysosomal positioning via TMEM55B phosphorylation
Authors: Araki Makoto , Kontani Kenji
Published: January 2021

Lysosomes are dynamic organelles that are transported along microtubules bidirectionally via kinesin and dynein motor proteins. Lysosomal positioning, which is determined by the balance of the bidirectional lysosomal movement, changes under various conditions and affects lysosomal functions such as autophagy and antigen presentation. A recent study by Takemasu et al. (Phosphorylation of TMEM55B by Erk/MAPK regulates lysosomal positioning. J. Biochem. 2019; 166:175–185) has shown that phosphorylation of the transmembrane protein TMEM55B is involved in the retrograde lysosomal trafficking towards the perinuclear region. They found that TMEM55B is phosphorylated upon stimulation with various ligands and that Erk/MAPK mediates the TMEM55B phosphorylation. They have also revealed that a phosphorylation mimic mutant of TMEM55B enhances perinuclear lysosomal clustering compared to the wild-type TMEM55B. These findings suggest that TMEM55B phosphorylation by Erk/MAPK is responsible for regulating lysosomal positioning in response to external stimuli.
Thioredoxin pathway in Anabaena sp. PCC 7120: activity of NADPH-thioredoxin reductase C
Authors: Deschoenmaeker Frédéric , Mihara Shoko , Niwa Tatsuya , Taguchi Hideki , Wakabayashi Ken-Ichi , Toyoshima Masakazu , Shimizu Hiroshi , Hisabori Toru
Published: January 2021

To understand the physiological role of NADPH-thioredoxin reductase C (NTRC) in cyanobacteria, we investigated an NTRC-deficient mutant strain of Anabaena sp., PCC 7120, cultivated under different regimes of nitrogen supplementation and light exposure. The deletion of ntrC did not induce a change in the cell structure and metabolic pathways. However, time-dependent changes in the abundance of specific proteins and metabolites were observed. A decrease in chlorophyll a was correlated with a decrease in chlorophyll a biosynthesis enzymes and photosystem I subunits. The deletion of ntrC led to a deregulation of nitrogen metabolism, including the NtcA accumulation and heterocyst-specific proteins while nitrate ions were available in the culture medium. Interestingly, this deletion resulted in a redox imbalance, indicated by higher peroxide levels, higher catalase activity and the induction of chaperones such as MsrA. Surprisingly, the antioxidant protein 2-CysPrx was downregulated. The deficiency in ntrC also resulted in the accumulation of metabolites such as 6-phosphogluconate, ADP and ATP. Higher levels of NADP+ and NADPH partly correlated with higher G6PDH activity. Rather than impacting protein expression levels, NTRC appears to be involved in the direct regulation of enzymes, especially during the dark-to-light transition period.
First Report of Insecticide Resistance to Organophosphates and Pyrethroids in the Small Hive Beetle (Coleoptera: Nitidulidae) and Development of a Resistance Monitoring Technique
Authors: Kanga Lambert H B , Marechal Walker , Legaspi Jesusa C , Haseeb Muhammad
Published: January 2021

The small hive beetle, Aethina tumida Murray (Coleoptera: Nitidulidae), is a serious threat to the honey bee industry, which relies on chemicals for the control of major honey bee pests. We developed a glass vial bioassay for resistance monitoring of adult A. tumida populations in honey bee colonies. We also determined concentrations that could be used to discriminate between susceptible and resistant strains. These include the pyrethroids cypermethrin (25.0 μg per vial) and fluvalinate (25.0 μg per vial) and the organophosphates malathion (10.0 μg per vial), chlorpyrifos (2.5 μg per vial), and coumaphos (25.0 μg per vial). Here, we report that resistance to fluvalinate and coumaphos was widespread in A. tumida populations in Florida in 2019. Aethina tumida populations were still susceptible to cypermethrin, malathion, and chlorpyrifos. The levels of resistance differed between pyrethroid and organophosphate insecticides. Over the last 10 yr, A. tumida populations have developed 43.7-fold resistance to coumaphos and 5.4-fold to fluvalinate. The levels of insecticide resistance were not similar within insecticides in the same class, which suggest that this type of resistance is manageable. Our results demonstrate the usefulness of glass vial bioassays to detect resistance in adult A. tumida and provide the foundation for a resistance management strategy. To the best of our knowledge, this is the first report of insecticide resistance in small hive beetle populations and suggests an urgent need for alternative control strategies for these serious pests of honey bee colonies.
Ameliorative effects of garlic oil on FNDC5 and irisin sensitivity in liver of streptozotocin-induced diabetic rats
Authors: Eser Nadire , Yoldas Atila , Turk Ahmet , Kalaycı Yigin Aysel , Yalcin Alper , Cicek Mustafa
Published: January 2021

Objectives

This study was aimed to investigate the effects of garlic oil (GO), an important natural constituent used in alleviating diabetes and its complications, on the expression levels of irisin and related genes.

Methods

Thirty-two rats were divided into four groups: Control, Diabetes-Control, Diabetes+GO 100 mg/kg/day and Control+GO 100 mg/kg/day for 45 days. The measurements included: changes in liver Peroxisome proliferator-activated receptor-gamma-coactivator (PGC)-1α, Fibronectin Type-III-Domain-Containing5 (FNDC5), irisin expression, mRNA expression of p38 and TNF-α (Tumour necrosis factor-α), total-antioxidant-status (L-TAS; S-TAS), total-oxidant-status (L-TOS; S-TOS) in liver and serum, respectively.

Key findings

There was a significant reduction in serum levels of irisin and S-TAS and expression of PGC-1α and FNDC5 in liver in Diabetes-control compared to Control-group, while a significant increase in serum levels of fasting blood glucose (FBG) and TOS, also p38 and TNF-α expressions in liver. In Diabetes+GO group, there was a significant increase in serum irisin and S-TAS, also expression of PGC-1α and FNDC5 in liver, while serum FBG, S-TOS levels, and mRNA expression of p38 and TNF-α in liver were decreased compared to Diabetes-control group (P < 0.05).

Conclusions

GO alleviated the diabetic liver injury by decreasing Oxidative-Stress parameters and regulation PGC-lα, FNDC5, irisin and P38, keeping the balance of TAS/TOS and TNF-α.
Dual-modality emergency management of a rare cause of an aorto-oesophageal fistula: a case report
Authors: Vasanthan Rishi , Tabbakh Yasmin , Doran Sophie , Baker Daryll , Hague Julian , Qureshi Yassar , Dawas Khaled , Mohammadi Borzoueh
Published: January 2021

Aorto-oesophageal fistula (AOF) is a life-threatening condition that usually presents with upper gastro-intestinal haemorrhage. This case report details the emergency presentation and management of a 51-year-old male who presented with hematemesis secondary to an impacted denture (ingested two years previously) in the oesophagus that had led to an AOF. This necessitated urgent thoracic endovascular aortic repair followed by thoracotomy, oesophagotomy, T-tube insertion and oesophagostomy. This is the first documentation in the literature of the dual-modality management for this rare cause of AOF and demonstrates the multidisciplinary approach to successful management of this complex yet rare presentation.
Overproduction of ascorbic acid impairs pollen fertility in tomato
Authors: Deslous Paul , Bournonville Céline , Decros Guillaume , Okabe Yoshihiro , Mauxion Jean-Philippe , Jorly Joana , Gadin Stéphanie , Brès Cécile , Mori Kentaro , Ferrand Carine , Prigent Sylvain , Ariizumi Tohru , Ezura Hiroshi , Hernould Michel , Rothan Christophe , Pétriacq Pierre , Gibon Yves , Baldet Pierre
Published: January 2021

Ascorbate is a major antioxidant buffer in plants. Several approaches have been used to increase the ascorbate content of fruits and vegetables. Here, we combined forward genetics with mapping-by-sequencing approaches using an ethyl methanesulfonate (EMS)-mutagenized Micro-Tom population to identify putative regulators underlying a high-ascorbate phenotype in tomato fruits. Among the ascorbate-enriched mutants, the family with the highest fruit ascorbate level (P17C5, up to 5-fold wild-type level) had strongly impaired flower development and produced seedless fruit. Genetic characterization was performed by outcrossing P17C5 with cv. M82. We identified the mutation responsible for the ascorbate-enriched trait in a cis-acting upstream open reading frame (uORF) involved in the downstream regulation of GDP-l-galactose phosphorylase (GGP). Using a specific CRISPR strategy, we generated uORF-GGP1 mutants and confirmed the ascorbate-enriched phenotype. We further investigated the impact of the ascorbate-enriched trait in tomato plants by phenotyping the original P17C5 EMS mutant, the population of outcrossed P17C5 × M82 plants, and the CRISPR-mutated line. These studies revealed that high ascorbate content is linked to impaired floral organ architecture, particularly anther and pollen development, leading to male sterility. RNA-seq analysis suggested that uORF-GGP1 acts as a regulator of ascorbate synthesis that maintains redox homeostasis to allow appropriate plant development.
Finitism, imperative programs and primitive recursion
Authors: Leivant Daniel
Published: January 2021

Following the Crisis of Foundations Hilbert proposed to consider a finitistic form of arithmetic as mathematics’ safe core. This approach to finitism has often admitted primitive recursive function definitions as obviously finitistic, but some have advocated the inclusion of additional variants of recurrence, while others argued that, to the contrary, primitive recursion exceeds finitism. In a landmark essay, William Tait contested the finitistic nature of these extensions, due to their impredicativity, and advocated identifying finitism with primitive recursive arithmetic, a stance often referred to as Tait’s Thesis. However, a problem with Tait’s argument is that the recurrence schema has itself impredicative and non-finitistic facets, starting with an explicit reference to the functions being defined, which are after all infinite objects. It is therefore desirable to buttress Tait’s Thesis on grounds that avoid altogether any trace of concrete infinities or impredicativity. We propose here to do just that, building on the generic framework of [ 13].

We provide further evidence for Tait’s Thesis by outlining a proof of a purely finitistic version of Parsons’ theorem, whose intuitive gist is that finitistic reasoning is equivalent to finitistic computing.
Banal bordering: Everyday encounters between migrants and security officers
Authors: Innes Alexandria J
Published: January 2021

The encounter between a migrant and the state is almost always fraught. The power of the state to approve or deny immigration status produces a power imbalance whereby the migrant is subject to the whim of the state. This research extracts encounters between migrants, police, immigration officers, and interpreters in the UK to conceptualise how the minutia of these encounters, and the standardised practices they involve, might impact the ability of migrants to express themselves and exercise their own voice in interactions. Adopting a reflexive ethnographic methodology, and using data gathered with police workers as a pilot case, I consider how the varied objectives of agencies and actors in the migration sector intersect with migrant experiences in practice. Ultimately, implications for migrant security lie in the recognition that migrant voice can be obscured as a result of mundane and everyday procedures. Banal bordering processes can go unnoticed and unaddressed by policy makers, but are often loaded with meaning for migrants subject to them. The vulnerability of migrants and the unbalanced nature of encounters between migrants and the state highlights how state power manifests at an everyday level, suggesting that insecurity is not unique to migrants without documents, but is present in all encounters between migrants and the state. Nevertheless, the professionals who are interacting with migrants are often in a position whereby they have the experiential expertise to offer workable, though limited, solutions, although they do not always have access to the channels or the resources necessary to implement them.
Efficacy of Weight Loss Interventions in United States Active Duty Military Populations: A Systematic Review
Authors: Csizmar Geralyn T , Irwin Melinda
Published: January 2021

Background

Since the beginning of overseas contingency operations, the percent of service members who are considered overweight or obese has tripled to 15% for men and 20% for women. This has implications for national security if the country is unable to staff its military with fit-to-fight individuals. The purpose of this systematic review is to move policy efforts forward by illuminating the efficacy of several lifestyle interventions for active duty service members since 2001. It aims to both identify common aspects of successful interventions and also identify interventions without success so DoD leaders may replace those initiatives.

Materials and Methods

The electronic database PubMed was searched from September 11, 2001 to May 15, 2020. Studies were included if the target population was United States active duty service members from any branch, the study included an intervention, and the measured outcome was weight loss. Seven studies met final inclusion criteria.

Results

Interventions with corresponding weight loss data are summarized in Table III. This review found that there is not a sufficient body of evidence to determine if interventions to aid active duty service members in losing weight are effective.

Conclusion

However, as a collection, the studies could support the notion that military members get the best results when interventions are convenient, modern, personalized, and accessible. More studies are needed, and future studies with larger sample sizes and longer durations would be valuable in determining efficacy of weight loss interventions. Undoubtedly, enrollment and compliance is difficult with military member moves and competing mission requirements. Ideally, the DoD should work to aggregate the efforts in this field, as many initiatives are not captured, shared, and utilized by other installations or other services. Data silos and unpublished or underdeveloped research reactively addresses issues and does not proactively address them. Policy change will need to be nested in further research, as well as consider the food environment on bases and possible prevention efforts.
New star clusters discovered towards the Galactic bulge direction using Gaia DR2
Authors: Ferreira F A , Corradi W J B , Maia F F S , Angelo M S , Santos J F C
Published: January 2021

We report the discovery of 34 new open clusters and candidates as a result of a systematic search carried out in 200 adjacent fields of 1 × 1 deg2 area projected towards the Galactic bulge, using Gaia DR2 data. The objects were identified and characterized by a joint analysis of their photometric, kinematic, and spatial distribution that has been consistently used and proved to be effective in our previous works. The discoveries were validated by cross-referencing the objects position and astrometric parameters with the available literature. Besides their coordinates and astrometric parameters, we also provide sizes, ages, distances, and reddening for the discovered objects. In particular, 32 clusters are closer than 2 kpc from the Sun, which represents an increment of nearly $39{{\ \rm per\ cent}}$ of objects with astrophysical parameters determined in the nearby inner disc. Although these objects fill an important gap in the open clusters distribution along the Sagittarius arm, this arm, traced by known clusters, appears to be interrupted, which may be an artefact due to the incompleteness of the cluster census.
SDSS-IV MaNGA: the ‘G-dwarf problem’ revisited
Authors: Greener Michael J , Merrifield Michael , Aragón-Salamanca Alfonso , Peterken Thomas , Andrews Brett , Lane Richard R
Published: January 2021

The levels of heavy elements in stars are the product of enhancement by previous stellar generations, and the distribution of this metallicity among the population contains clues to the process by which a galaxy formed. Most famously, the ‘G-dwarf problem’ highlighted the small number of low-metallicity G-dwarf stars in the Milky Way, which is inconsistent with the simplest picture of a galaxy formed from a ‘closed box’ of gas. It can be resolved by treating the Galaxy as an open system that accretes gas throughout its life. This observation has classically only been made in the Milky Way, but the availability of high-quality spectral data from SDSS-IV MaNGA and the development of new analysis techniques mean that we can now make equivalent measurements for a large sample of spiral galaxies. Our analysis shows that high-mass spirals generically show a similar deficit of low-metallicity stars, implying that the Milky Way’s history of gas accretion is common. By contrast, low-mass spirals show little sign of a G-dwarf problem, presenting the metallicity distribution that would be expected if such systems evolved as pretty much closed boxes. This distinction can be understood from the differing timescales for star formation in galaxies of differing masses.
Diversification of CD1 Molecules Shapes Lipid Antigen Selectivity
Authors: Paterson Nicole M , Al-Zubieri Hussein , Barber Matthew F
Published: January 2021

Molecular studies of host–pathogen evolution have largely focused on the consequences of variation at protein–protein interaction surfaces. The potential for other microbe-associated macromolecules to promote arms race dynamics with host factors remains unclear. The cluster of differentiation 1 (CD1) family of vertebrate cell surface receptors plays a crucial role in adaptive immunity through binding and presentation of lipid antigens to T-cells. Although CD1 proteins present a variety of endogenous and microbial lipids to various T-cell types, they are less diverse within vertebrate populations than the related major histocompatibility complex (MHC) molecules. We discovered that CD1 genes exhibit a high level of divergence between simian primate species, altering predicted lipid-binding properties and T-cell receptor interactions. These findings suggest that lipid–protein conflicts have shaped CD1 genetic variation during primate evolution. Consistent with this hypothesis, multiple primate CD1 family proteins exhibit signatures of repeated positive selection at surfaces impacting antigen presentation, binding pocket morphology, and T-cell receptor accessibility. Using a molecular modeling approach, we observe that interspecies variation as well as single mutations at rapidly-evolving sites in CD1a drastically alter predicted lipid binding and structural features of the T-cell recognition surface. We further show that alterations in both endogenous and microbial lipid-binding affinities influence the ability of CD1a to undergo antigen swapping required for T-cell activation. Together these findings establish lipid–protein interactions as a critical force of host–pathogen conflict and inform potential strategies for lipid-based vaccine development.
Genome-Scale Profiling Reveals Noncoding Loci Carry Higher Proportions of Concordant Data
Authors: Literman Robert , Schwartz Rachel
Published: January 2021

Many evolutionary relationships remain controversial despite whole-genome sequencing data. These controversies arise, in part, due to challenges associated with accurately modeling the complex phylogenetic signal coming from genomic regions experiencing distinct evolutionary forces. Here, we examine how different regions of the genome support or contradict well-established relationships among three mammal groups using millions of orthologous parsimony-informative biallelic sites (PIBS) distributed across primate, rodent, and Pecora genomes. We compared PIBS concordance percentages among locus types (e.g. coding sequences (CDS), introns, intergenic regions), and contrasted PIBS utility over evolutionary timescales. Sites derived from noncoding sequences provided more data and proportionally more concordant sites compared with those from CDS in all clades. CDS PIBS were also predominant drivers of tree incongruence in two cases of topological conflict. PIBS derived from most locus types provided surprisingly consistent support for splitting events spread across the timescales we examined, although we find evidence that CDS and intronic PIBS may, respectively and to a limited degree, inform disproportionately about older and younger splits. In this era of accessible wholegenome sequence data, these results:1) suggest benefits to more intentionally focusing on noncoding loci as robust data for tree inference and 2) reinforce the importance of accurate modeling, especially when using CDS data.