bluuebunny/crossref_metadata_2025 huggingface dataset:
Morphological Covariance and Onset of Foot Prehensility as Indicators of Integrated Evolutionary Dynamics in the Herons (Ardeidae)
Authors: Riegner M F , Bassar R D
Published: March 2023

Synopsis

The ultimate form an organism attains is based, in part, on the rate and timing of developmental trajectories and on compensatory relationships between morphological traits. For example, there is often an inverse correlation between the relative size of an organism's head and the length of its legs. Avian examples with a disproportionately small head and long legs include ostriches (Struthionidae), flamingos (Phoenicopteridae), cranes (Gruidae), and stilts (Recurvirostridae). To determine whether a possible compensatory relationship exists between relative head size and hind-limb length in a typically long-legged family of birds—the Ardeidae—we measured and analyzed skull dimensions (length, width, and height of cranium, and bill length) and skeletal hind-limb dimensions (femur, tibiotarsus, and tarsometatarsus) of the 12 North American species (north of Mexico) and of 12 additional taxa, including the morphologically divergent Agamia and Cochlearius. We found that Ardea species exhibit the smallest relative head sizes associated with the longest legs, while Butorides, Nycticorax, Nyctanassa, and Cochlearius have among the largest heads relative to hind-limb length. Furthermore, both positive and negative allometries occur in paired comparisons between the three hind-limb bones, expressed in tall morphotypes having disproportionately short femurs while short-legged morphotypes exhibit disproportionately long femurs; we show that this relationship has implications for foraging behavior. Moreover, the nestlings of short-legged herons exhibit functional precociality of the hind limbs through an early onset of prehensile ability of the feet to grasp branches, which is later expressed in adult foraging mode. This developmentally accelerated prehensile function in small-bodied species may be attributed, in part, to selection for predator avoidance in the early nestling stage.
Impact ofompk36genotype and KPC subtype on thein vitroactivity of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam against KPC-producingK. pneumoniaeclinical isolates
Authors: Rogers Tara M , Kline Ellen G , Griffith Marissa P , Jones Chelsea E , Rubio Abigail M , Squires Kevin M , Shields Ryan K
Published: March 2023

Objectives

The availability of new β-lactam/β-lactamase inhibitors ceftazidime/avibactam, meropenem/vaborbactam and imipenem/relebactam have redefined contemporary treatment of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) infections. We aimed to characterize and contrast the in vitro activity of these agents against genetically diverse KPC-Kp clinical isolates.

Methods

We analysed genomes of 104 non-consecutive KPC-Kp isolates and compared the in vitro antibiotic activity by KPC subtype and ompK36 genotype. MICs were determined in triplicate by CLSI methods. Twenty representative isolates were selected for time–kill analyses against physiological steady-state and trough concentrations, as well as 4× MIC for each agent.

Results

Fifty-eight percent and 42% of isolates harboured KPC-2 and KPC-3, respectively. OmpK36 mutations were more common among KPC-2- compared with KPC-3-producing Kp (P < 0.0001); mutations were classified as IS5 insertion, glycine-aspartic acid insertion at position 134 (GD duplication) and other mutations. Compared to isolates with WT ompK36, ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam MICs were elevated for isolates with IS5 by 2-, 4- and 16-fold, respectively (P < 0.05 for each). Against isolates with GD duplication, imipenem/relebactam and meropenem/vaborbactam MICs were increased, but ceftazidime/avibactam MICs were not. In time–kill studies, ceftazidime/avibactam-mediated killing correlated with ceftazidime/avibactam MICs, and did not vary across ompK36 genotypes. Imipenem/relebactam was not bactericidal against any isolate at trough concentrations. At steady-state imipenem/relebactam concentrations, regrowth occurred more commonly for isolates with IS5 mutations. Log-kills were lower in the presence of meropenem/vaborbactam for isolates with GD duplication compared with IS5 mutations.

Conclusions

Our investigation identified key genotypes that attenuate, to varying degrees, the in vitro activity for each of the new β-lactam/β-lactamase inhibitors. Additional studies are needed to translate the importance of these observations into clinical practice.
Role of previous systemic antibiotic therapy on the probability of recurrence after an initial episode of Clostridioides difficile infection treated with vancomycin
Authors: Merchante Nicolás , Herrero Rocío , Valverde-Fredet María Dolores , Rodríguez-Fernández Miguel , Pinargote Héctor , Martínez-Marcos Francisco J , Gil-Anguita Concepción , García-López María , Tasias Pitarch María , Abril López De Medrano Vicente , Navarrete Lorite Miguel Nicolás , Gómez-Ayerbe Cristina , León Eva , González-De La Aleja Pilar , Ruiz Castillo Ana , Aller Ana I , Rodríguez Juan Carlos , Ternero Fonseca Julia , Corzo Juan E , Naranjo Pérez Alberto , Trigo-Rodríguez Marta , Merino Esperanza
Published: March 2023

Objectives

To investigate the role of previous antibiotic therapy in the risk of recurrence after a Clostridioides difficile infection (CDI) treated with vancomycin.

Methods

Multicentre observational study. Patients with a CDI episode achieving clinical cure with oral vancomycin and followed up 8 weeks were included. Previous antibiotic exposure up to 90 days was collected. Multivariate analysis of predictors of recurrence adjusted by the propensity score (PS) of being previously treated with each non-CDI antibiotic was performed.

Results

Two hundred and forty-one patients were included; 216 (90%) had received systemic antibiotics. Fifty-three patients (22%) had a CDI recurrence. Rates of recurrence were lower in those treated with piperacillin/tazobactam in the last month when compared with those not receiving piperacillin/tazobactam [3 (7%) versus 50 (25%); P = 0.01], whereas higher rates were seen in those treated with cephalosporins in the last month [26/87 (30%) versus 27/154 (17%); P = 0.03]. In multivariate analysis controlled by the inverse probability of treatment weighting by PS, receiving ≥5 days of piperacillin/tazobactam in the last month as the last antibiotic regimen prior to CDI was independently associated with a lower risk of recurrence [adjusted OR (AOR) 0.13; 95% CI: 0.06–0.29; P < 0.0001] whereas exposure for ≥5 days to cephalosporins (versus piperacillin/tazobactam) was associated with an increased risk (AOR 10.9; 95% CI: 4.4–27.1; P < 0.0001).

Conclusions

Recent use of piperacillin/tazobactam might be associated with a lower risk of CDI recurrence, while recent use of cephalosporins might promote an increased risk. These findings should be considered when treating hospitalized patients.
Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children’s Oncology Group
Authors: Martin-Giacalone Bailey A , Richard Melissa A , Scheurer Michael E , Khan Javed , Sok Pagna , Shetty Priya B , Chanock Stephen J , Li Shengchao Alfred , Yeager Meredith , Marquez-Do Deborah A , Barkauskas Donald A , Hall David , McEvoy Matthew T , Brown Austin L , Sabo Aniko , Scheet Paul , Huff Chad D , Skapek Stephen X , Hawkins Douglas S , Venkatramani Rajkumar , Mirabello Lisa , Lupo Philip J
Published: March 2023

Background

Relative to other pediatric cancers, survival for rhabdomyosarcoma (RMS) has not improved in recent decades, suggesting the need to enhance risk stratification. Therefore, we conducted a genome-wide association study for event-free survival (EFS) and overall survival (OS) to identify genetic variants associated with outcomes in individuals with RMS.

Methods

The study included 920 individuals with newly diagnosed RMS who were enrolled in Children’s Oncology Group protocols. To assess the association of each single nucleotide polymorphism (SNP) with EFS and OS, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using multivariable Cox proportional hazards models, adjusted for clinical covariates. All statistical tests were two sided. We also performed stratified analyses by histological subtype (alveolar and embryonal RMS) and carried out sensitivity analyses of statistically significant SNPs by PAX3/7-FOXO1 fusion status and genetic ancestry group.

Results

We identified that rs17321084 was associated with worse EFS (HR = 2.01, 95% CI = 1.59 to 2.53, P = 5.39 × 10−9) and rs10094840 was associated with worse OS (HR = 1.84, 95% CI = 1.48 to 2.27, P = 2.13 × 10−8). Using publicly available data, we found that rs17321084 lies in a binding region for transcription factors GATA2 and GATA3, and rs10094840 is associated with SPAG1 and RNF19A expression. We also identified that CTNNA3 rs2135732 (HR = 3.75, 95% CI = 2.34 to 5.99, P = 3.54 × 10−8) and MED31 rs74504320 (HR = 3.21, 95% CI = 2.12 to 4.86, P = 3.60 × 10−8) were associated with worse OS among individuals with alveolar RMS.

Conclusions

We demonstrated that common germline variants are associated with EFS and OS among individuals with RMS. Additional replication and investigation of these SNP effects may further support their consideration in risk stratification protocols.
Effects of floral traits on geitonogamous selfing rates and reproductive success in a protandrous species
Authors: Hou Meng , Zhao Zhi-Gang
Published: March 2023

Through its role in regulating pollinator behavior, floral display size and nectar gradient within inflorescences may alter the extent of geitonogamy and thus female reproductive success in protandrous species. However, this has seldom been examined. By quantifying selfing rate, seed number and male donor number, we estimated the effects of floral display size, nectar gradient and their interactions on plant reproduction in protandrous Aconitum gymnandrum. At plant level, selfing rate and seed number increased with a larger floral display of both main and lateral inflorescences but reduced with a declining nectar gradient. The effects of floral display of the main inflorescence on selfing rate and seed number were altered by the nectar gradient and floral display of lateral inflorescences as shown by their interactions. Larger floral display of the main inflorescence reduced male donor diversity. At flower level, the selfing rate and the seed number varied among flower positions, in which bottom flowers had lower selfing rate and higher seed number than top flowers. The effects of floral traits on geitonogamous selfing rate and seed number were inconsistent among flower positions. Although low cost of geitonogamous selfing for reproduction was tested by hand-pollination, the selfing rate was negatively correlated with seed number and male donor number in open-pollinated population. Our results suggest the potential role of trade-off between geitonogamy cost and reproductive benefit in evolution of floral traits. The variation of selfing rate and reproductive success among flowers may alter the trade-off and thus complicate evolution of traits.
The combination of astragaloside IV and Panax notoginseng saponins attenuates cerebral ischaemia–reperfusion injury in rats through ferroptosis and inflammation inhibition via activating Nrf2
Authors: Kang Zhineng , Xiao Qian , Wang Linlin , Xiao Lan , Tang Biao
Published: March 2023

Objectives

This study aimed to observe the effect of the combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) on cerebral ischaemia–reperfusion injury (CIRI) and explore the specific mechanism of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated combination of AST IV and PNS against CIRI based on ferroptosis and inflammatory response.

Methods

The therapeutic effect and mechanism of AST IV and PNS were evaluated by constructing a Sprague–Dawley rat middle cerebral artery ischaemia–occlusion–reperfusion model. The specific mechanism of the combination of AST IV and PNS against CIRI was revealed through the combined intervention of the Nrf2-specific inhibitor brusatol.

Key findings

After AST IV and PNS treatment, the cerebral infarction area of the rats was reduced; behavioural performance was improved; Fe2+, malondialdehyde, lipid peroxidation, interleukin-6, interleukin-1β, tumour necrosis factor-α and myeloperoxidase levels were reduced; and glutathione and glutathione peroxidase 4 levels were increased. In addition, the expression of Nrf2 was significantly increased, the combined treatment was more effective than the single treatment, and the Nrf2 inhibitor brusatol could reverse the effects of the combined intervention of AST IV and PNS.

Conclusions

The findings of this study suggest that combining AST IV and PNS attenuates CIRI by activating Nrf2 to inhibit ferroptosis and inflammatory responses.
CLPB3 is required for the removal of chloroplast protein aggregates and thermotolerance in Chlamydomonas
Authors: Kreis Elena , Niemeyer Justus , Merz Marco , Scheuring David , Schroda Michael
Published: March 2023

In the cytosol of plant cells, heat-induced protein aggregates are resolved by the CASEIN LYTIC PROTEINASE/HEAT SHOCK PROTEIN 100 (CLP/HSP100) chaperone family member HSP101, which is essential for thermotolerance. For the chloroplast family member CLPB3 this is less clear, with controversial reports on its role in conferring thermotolerance. To shed light on this issue, we have characterized two clpb3 mutants in Chlamydomonas reinhardtii. We show that chloroplast CLPB3 is required for resolving heat-induced protein aggregates containing stromal TRIGGER FACTOR (TIG1) and the small heat shock proteins 22E/F (HSP22E/F) in vivo, and for conferring thermotolerance under heat stress. Although CLPB3 accumulation is similar to that of stromal HSP70B under ambient conditions, we observed no prominent constitutive phenotypes. However, we found decreased accumulation of the PLASTID RIBOSOMAL PROTEIN L1 (PRPL1) and increased accumulation of the stromal protease DEG1C in the clpb3 mutants, suggesting that a reduction in chloroplast protein synthesis capacity and an increase in proteolytic capacity may compensate for loss of CLPB3 function. Under ambient conditions, CLPB3 was distributed throughout the chloroplast, but reorganized into stromal foci upon heat stress, which mostly disappeared during recovery. CLPB3 foci were localized next to HSP22E/F, which accumulated largely near the thylakoid membranes. This suggests a possible role for CLPB3 in disentangling protein aggregates from the thylakoid membrane system.
High temperature defense pathways mediate lodicule expansion and spikelet opening in maize tassels
Authors: Liu Xiaoli , Gu Mingqi , Lv Xuanlong , Sheng Dechang , Wang Xin , Wang Pu , Huang Shoubing
Published: March 2023

High temperature (HT) at flowering hinders pollen shedding, but the mechanisms underlying stress-induced spikelet closure are poorly understood in maize. In this study, yield components, spikelet opening, and lodicule morphology/protein profiling upon HT stress during flowering were examined in two contrasting maize inbred lines, Chang 7-2 and Qi 319. HT induced spikelet closure and reduced pollen shed weight (PSW) and seed set in both lines, but Qi 319 had a 7-fold lower PSW than Chang 7-2, and was thus more susceptible to HT. In Qi 319, a smaller lodicule size reduced the spikelet opening rate and angle, and relatively more vascular bundles hastened lodicule shrinking compared with Chang 7-2. Lodicules were collected for proteomics analysis. In lodicules of HT-stressed plants, proteins involved in stress signals, cell wall, cell constructure, carbohydrate metabolism, and phytohormone signaling were associated with stress tolerance. HT down-regulated the expression of ADP-ribosylation factor GTPase-activating protein domain2, SNAP receptor complex member11, and sterol methyltransferase2 in Qi 319 but not in Chang 7-2, which was in good agreement with the observed changes in protein abundance. Exogenous epibrassinolide increased the spikelet opening angle and extended the duration of spikelet opening. These results suggest that dysfunction of the actin cytoskeleton and membrane remodeling induced by HT probably limits lodicule expansion. In addition, a reduction in the vascular bundles in the lodicules and application of epibrassinolide might confer spikelet tolerance to HT stress.
The 3D genome and its impacts on human health and disease
Authors: Wang Siqi , Luo Zhengyu , Liu Weiguang , Hu Tengfei , Zhao Zhongying , Rosenfeld Michael G , Song Xiaoyuan
Published: March 2023

Eukaryotic genomes are highly compacted in the cell nucleus. Two loci separated by a long linear distance can be brought into proximity in space through DNA-binding proteins and RNAs, which contributes profoundly to the regulation of gene expression. Recent technology advances have enabled the development and application of the chromosome conformation capture (3C) technique and a host of 3C-based methods that enable genome-scale investigations into changes in chromatin high-order structures during diverse physiological processes and diseases. In this review, we introduce 3C-based technologies and discuss how they can be utilized to glean insights into the impacts of three-dimensional (3D) genome organization in normal physiological and disease processes.
Ablation of Mea6/cTAGE5 in oligodendrocytes significantly impairs white matter structure and lipid content
Authors: Ma Tiantian , Mao Wei , Zhang Shaohua , Wang Yaqing , Wang Tao , Liu Jinghua , Shi Lei , Yu Xiang , Xue Rong , Shui Guanghou , Xu Zhiheng
Published: March 2023

Lipid-rich myelin is a special structure formed by oligodendrocytes wrapping neuronal axons. Abnormal myelin sheath is associated with many neurological diseases. Meningioma-expressed antigen 6 (Mea6)/cutaneous T cell lymphoma-associated antigen 5C (cTAGE5C) plays an important role in vesicle trafficking from the endoplasmic reticulum (ER) to Golgi, and conditional knockout (cKO) of Mea6 in the brain significantly affects neural development and brain function. However, whether the impaired brain function involves the development of oligodendrocytes and white matter beyond neurons remains unclear. In this study, by using different models of diffusion magnetic resonance imaging, we showed that cKO of Mea6 in oligodendrocytes leads to significant impairment of the gross and microstructure of the white matter, as well as a significant decrease of cholesterol and triglycerides in brains. Our lipidomic analysis of purified myelin sheath for the first time showed that Mea6 elimination in oligodendrocytes significantly altered the lipid composition in myelin lipidome, especially the proportion of very long chain fatty acids (VLCFAs). In particular, the levels of most VLCFA-containing phosphatidylcholines were substantially lower in the myelin sheath of the cKO mice. The reduction of VLCFAs is likely due to the downregulated expression of elongation of very long chain fatty acids (ELOVLs). Our study of an animal model with white matter malformation and the comprehensive lipid profiling would provide clues for future studies of the formation of myelin sheath, myelin lipids, and the pathogenesis of white matter diseases.
Accurate model of the projected velocity distribution of galaxies in dark matter haloes
Authors: Aung Han , Nagai Daisuke , Rozo Eduardo , Wolfe Brandon , Adhikari Susmita
Published: March 2023

We present a per cent-level accurate model of the line-of-sight velocity distribution of galaxies around dark matter haloes as a function of projected radius and halo mass. The model is developed and tested using synthetic galaxy catalogues generated with the UniverseMachine run on the Multi-Dark Planck 2 N-body simulations. The model decomposes the galaxies around a cluster into three kinematically distinct classes: orbiting, infalling, and interloping galaxies. We demonstrate that: (1) we can statistically distinguish between these three types of galaxies using only projected line-of-sight velocity information; (2) the halo edge radius inferred from the line-of-sight velocity dispersion is an excellent proxy for the three-dimensional halo edge radius; and (3) we can accurately recover the full velocity dispersion profile for each of the three populations of galaxies. Importantly, the velocity dispersion profiles of the orbiting and infalling galaxies contain five independent parameters – three distinct radial scales and two velocity dispersion amplitudes – each of which is correlated with mass. Thus, the velocity dispersion profile of galaxy clusters has inherent redundancies that allow us to perform non-trivial systematics checks from a single data set. We discuss several potential applications of our new model for detecting the edge radius and constraining cosmology and astrophysics using upcoming spectroscopic surveys.
Collisional evolution of dust and water ice in protoplanetary discs during and after an accretion outburst
Authors: Houge Adrien , Krijt Sebastiaan
Published: March 2023

Most protoplanetary discs are thought to undergo violent and frequent accretion outbursts, during which the accretion rate and central luminosity are elevated for several decades. This temporarily increases the disc temperature, leading to the sublimation of ice species as snowlines move outwards. In this paper, we investigate how an FUor-type accretion outburst alters the growth and appearance of dust aggregates at different locations in protoplanetary discs. We develop a model based on the Monte Carlo approach to simulate locally the coagulation and fragmentation of icy dust particles and investigate different designs for their structure and response to sublimation. Our main finding is that the evolution of dust grains located between the quiescent and outburst water snowlines is driven by significant changes in composition and porosity. The time required for the dust population to recover from the outburst and return to a coagulation/fragmentation equilibrium depends on the complex interplay of coagulation physics and outburst properties, and can take up to 4500 yr at 5 au. Pebble-sized particles, the building blocks of planetesimals, are either deprecated in water ice or completely destroyed, respectively, resulting in drier planetesimals or halting their formation altogether. When accretion outbursts are frequent events, the dust can be far from collisional equilibrium for a significant fraction of time, offering opportunities to track past outbursts in discs at millimetre wavelengths. Our results highlight the importance of including accretion outbursts in models of dust coagulation and planet formation.
Investigation of a small X-ray flaring event in NLS1 galaxy NGC 4051
Authors: Kumari Neeraj , Jana Arghajit , Naik Sachindra , Nandi Prantik
Published: March 2023

We performed a detailed broad-band spectral and timing analysis of a small flaring event of ∼120 ks in the narrow-line Seyfert 1 galaxy NGC 4051 using simultaneous XMM–Newton and NuSTAR observations. The ∼300 ks long NuSTAR observation and the overlapping XMM–Newton exposure were segregated into pre-flare, flare, and post-flare segments. During the flare, the NuSTAR count rate peaked at 2.5 times the mean count rate before the flare. Using various physical and phenomenological models, we examined the 0.3–50 keV X-ray spectrum, which consists of a primary continuum, reprocessed emission, warm absorber and ultrafast outflows at different time-scales. The mass of the central black hole is estimated to be ≥1.32 × 105 M⊙ from spectral analysis. The absence of correlation between the flux in the 6–7 keV and 10–50 keV bands suggests different origins of the iron emission line and the Compton hump. From the spectral analysis, we found that the reflection fraction drops significantly during the flare, accompanied by an increase in the coronal height above the disc. The spectrum became soft during the flare, supporting the ‘softer when brighter’ nature of the source. After the alleviation of the flare, the coronal height drops and the corona heats up. This indicates that there could be inflation of the corona during the flare. We found no significant change in the inner accretion disc or the seed photon temperature. These results suggest that the flaring event occurred due to a change in coronal properties rather than any notable change in the accretion disc.
A trail of the invisible: blue globular clusters trace the radial density distribution of the dark matter – case study of NGC 4278
Authors: Kluge Matthias , Remus Rhea-Silvia , Babyk Iurii V , Forbes Duncan A , Dolfi Arianna
Published: March 2023

We present new, deep optical observations of the early-type galaxy NGC 4278, which is located in a small loose group. We find that the galaxy lacks fine substructure, that is, it appears relaxed, out to a radius of ∼70 kpc. Our g- and i-band surface brightness profiles are uniform down to our deepest levels of ∼28 mag arcsec−2. This spans an extremely large radial range of more than 14 half-mass radii. Combined with archival globular cluster (GC) number density maps and a new analysis of the total mass distribution obtained from archival Chandra X-ray data, we find that the red GC subpopulation traces well the stellar mass density profile from 2.4 out to even 14 half-mass radii, while the blue GC subpopulation traces the total mass density profile of the galaxy over a large radial range. Our results reinforce the scenario that red GCs form mostly in situ along with the stellar component of the galaxy, while the blue GCs are more closely aligned with the total mass distribution in the halo and were accreted along with halo matter. We conclude that for galaxies where the X-ray emission from the hot halo is too faint to be properly observable and as such is not available to measure the dark matter profile, the blue GC population can be used to trace this dark matter component out to large radii.
Population III star formation in an X-ray background: III. Periodic radiative feedback and luminosity induced by elliptical orbits
Authors: Park Jongwon , Ricotti Massimo , Sugimura Kazuyuki
Published: March 2023

We model Pop III star formation in different FUV and X-ray backgrounds, including radiation feedback from protostars. We confirm previous results that a moderate X-ray background increases the number of Pop III systems per unit cosmological volume, but masses and multiplicities of the system are reduced. The stellar mass function also agrees with previous results, and we confirm the outward migration of the stars within the protostellar discs. We find that nearly all Pop III star systems are hierarchical, i.e. binaries of binaries. Typically, two equal-mass stars form near the centre of the protostellar disc and migrate outwards. Around these stars, mini-discs fragment forming binaries that also migrate outwards. Stars may also form at Lagrange points L4/L5 of the system. Afterwards, star formation becomes more stochastic due to the large multiplicity, and zero-metallicity low-mass stars can form when rapidly ejected from the disc. Stars in the disc often have eccentric orbits, leading to a periodic modulation of their accretion rates and luminosities. At the pericentre, due to strong accretion, the star can enter a red-supergiant phase reaching nearly Eddington luminosity in the optical bands (mAB ∼ 34 for a 100 M⊙ star at z = 6). During this phase, the star, rather than its nebular lines, can be observed directly by JWST, if sufficiently magnified by a gravitational lens. The ∼10 000 AU separations and high eccentricities of many Pop III star binaries in our simulations are favourable parameters for IMBH mergers – and gravitational waves emission – through orbital excitation by field stars.
RNA binding proteins Smaug and Cup induce CCR4–NOT-dependent deadenylation of the nanos mRNA in a reconstituted system
Authors: Pekovic Filip , Rammelt Christiane , Kubíková Jana , Metz Jutta , Jeske Mandy , Wahle Elmar
Published: March 2023

Posttranscriptional regulation of the maternal nanos mRNA is essential for the development of the anterior – posterior axis of the Drosophila embryo. The nanos RNA is regulated by the protein Smaug, which binds to Smaug recognition elements (SREs) in the nanos 3’-UTR and nucleates the assembly of a larger repressor complex including the eIF4E-T paralog Cup and five additional proteins. The Smaug-dependent complex represses translation of nanos and induces its deadenylation by the CCR4–NOT deadenylase. Here we report an in vitro reconstitution of the Drosophila CCR4–NOT complex and Smaug-dependent deadenylation. We find that Smaug by itself is sufficient to cause deadenylation by the Drosophila or human CCR4–NOT complexes in an SRE-dependent manner. CCR4–NOT subunits NOT10 and NOT11 are dispensable, but the NOT module, consisting of NOT2, NOT3 and the C-terminal part of NOT1, is required. Smaug interacts with the C-terminal domain of NOT3. Both catalytic subunits of CCR4–NOT contribute to Smaug-dependent deadenylation. Whereas the CCR4–NOT complex itself acts distributively, Smaug induces a processive behavior. The cytoplasmic poly(A) binding protein (PABPC) has a minor inhibitory effect on Smaug-dependent deadenylation. Among the additional constituents of the Smaug-dependent repressor complex, Cup also facilitates CCR4–NOT-dependent deadenylation, both independently and in cooperation with Smaug.
Design principles and functional basis of enantioselectivity of alanyl-tRNA synthetase and a chiral proofreader during protein biosynthesis
Authors: Sivakumar Koushick , Venkadasamy Vinitha Lakshmi , Amudhan Gurumoorthy , Ann Kezia J , Goud Gadela Karteek , Nayani Kiranmai , Gogoi Jotin , Kuncha Santosh Kumar , Mainkar Prathama S , Kruparani Shobha P , Sankaranarayanan Rajan
Published: March 2023

Homochirality of the cellular proteome is attributed to the L-chiral bias of the translation apparatus. The chiral specificity of enzymes was elegantly explained using the ‘four-location’ model by Koshland two decades ago. In accordance with the model, it was envisaged and noted that some aminoacyl-tRNA synthetases (aaRS) that charge larger amino acids are porous to D-amino acids. However, a recent study showed that alanyl-tRNA synthetase (AlaRS) can mischarge D-alanine and that its editing domain, but not the universally present D-aminoacyl-tRNA deacylase (DTD), is responsible for correcting the chirality-based error. Here, using in vitro and in vivo data coupled with structural analysis, we show that AlaRS catalytic site is a strict D-chiral rejection system and therefore does not activate D-alanine. It obviates the need for AlaRS editing domain to be active against D-Ala-tRNAAla and we show that it is indeed the case as it only corrects L-serine and glycine mischarging. We further provide direct biochemical evidence showing activity of DTD on smaller D-aa-tRNAs that corroborates with the L-chiral rejection mode of action proposed earlier. Overall, while removing anomalies in the fundamental recognition mechanisms, the current study further substantiates how chiral fidelity is perpetuated during protein biosynthesis.
On the dependent recognition of some long zinc finger proteins
Authors: Zuo Zheng , Billings Timothy , Walker Michael , Petkov Petko M , Fordyce Polly M , Stormo Gary D
Published: March 2023

The human genome contains about 800 C2H2 zinc finger proteins (ZFPs), and most of them are composed of long arrays of zinc fingers. Standard ZFP recognition model asserts longer finger arrays should recognize longer DNA-binding sites. However, recent experimental efforts to identify in vivo ZFP binding sites contradict this assumption, with many exhibiting short motifs. Here we use ZFY, CTCF, ZIM3, and ZNF343 as examples to address three closely related questions: What are the reasons that impede current motif discovery methods? What are the functions of those seemingly unused fingers and how can we improve the motif discovery algorithms based on long ZFPs’ biophysical properties? Using ZFY, we employed a variety of methods and find evidence for ‘dependent recognition’ where downstream fingers can recognize some previously undiscovered motifs only in the presence of an intact core site. For CTCF, high-throughput measurements revealed its upstream specificity profile depends on the strength of its core. Moreover, the binding strength of the upstream site modulates CTCF’s sensitivity to different epigenetic modifications within the core, providing new insight into how the previously identified intellectual disability-causing and cancer-related mutant R567W disrupts upstream recognition and deregulates the epigenetic control by CTCF. Our results establish that, because of irregular motif structures, variable spacing and dependent recognition between sub-motifs, the specificities of long ZFPs are significantly underestimated, so we developed an algorithm, ModeMap, to infer the motifs and recognition models of ZIM3 and ZNF343, which facilitates high-confidence identification of specific binding sites, including repeats-derived elements. With revised concept, technique, and algorithm, we can discover the overlooked specificities and functions of those ‘extra’ fingers, and therefore decipher their broader roles in human biology and diseases.
A library of sensitive position-specific scoring matrices for high-throughput identification of nuclear pore complex subunits
Authors: Ioannides Andreas N , Katsani Katerina R , Ouzounis Christos A , Promponas Vasilis J
Published: March 2023

The nuclear pore complex exhibits different manifestations across eukaryotes, with certain components being restricted to specific clades. Several studies have been conducted to delineate the nuclear pore complex composition in various model organisms. Due to its pivotal role in cell viability, traditional lab experiments, such as gene knockdowns, can prove inconclusive and need to be complemented by a high-quality computational process. Here, using an extensive data collection, we create a robust library of nucleoporin protein sequences and their respective family-specific position-specific scoring matrices. By extensively validating each profile in different settings, we propose that the created profiles can be used to detect nucleoporins in proteomes with high sensitivity and specificity compared to existing methods. This library of profiles and the underlying sequence data can be used for the detection of nucleoporins in target proteomes.
The Four Evangelical Theologies of Work
Authors: Lynn Andrew
Published: March 2023

This chapter begins with an account of an Evangelical seminary course on meaning and vocation, bringing out the degree to which such courses seek to relocate notions of sacred activity among evangelical laity. A review of texts targeting religious laity from 1940 to 1980 suggests the emergence of four different “theologies of work” within the American evangelical cultural space. All four approaches seek to identify and repudiate a Sunday-Monday gap that threatens to compartmentalize and sequester religious life to the world of “Sunday.” A final assessment lays out how faith and work has changed since the 1980s: leaders have incorporated Romantic-inspired notions of purposeful work that emphasize beauty, harmony, fulfillment of purpose, and personal integration. A final assessment of these trends argues that these efforts ultimately recover something previously laid claim to by the Puritans: a theology that could affirm the day-to-day life of the laity and the various non-ecclesial activities that make up the textures of everyday life.
Black is a Church
Authors: Sorett Josef
Published: March 2023

Across four chapters that proceed as chronologically organized episodes, Black is a Church maps the ways in which black American culture and identity have been animated by a particular set of often unmarked Protestant logics. In doing so, it tracks the entangled discourses of racial authenticity and religious orthodoxy as Christianity was made constitutive of the content and forms of black subjectivity and facilitated the emergence of black social life in North America. Chapter 1 argues that Afro-Protestantism relied upon literary strategies to enunciate itself since the earliest years of its formation. As seen in slave narratives, Protestant Christianity was essential to the establishment of the earliest black literary forms. Chapter 2 follows Afro-Protestantism’s heterodox history in the convergence of literature, politics, and religion at the end of the nineteenth century. This chapter tracks a set of social movements, revealing how religious aspirations animated early calls for a “race literature” and the “the color line” provided an organizing logic for religious innovations as divergent as the practices of pluralism and Pentecostalism at the century’s close. Chapter 3 surveys historical, sociological, and anthropological work during the 1930s and 1940s—focusing especially on the launch of Phylon: The Atlanta University Review of Race and Culture—at a key moment in the study of African American culture. Finally, chapter 4 presents three recent episodes, across the spheres of scholarship, literature, and politics, to illustrate the persistence—that is, the afterlives—of Afro-Protestantism at the turn of the twenty-first century.
The Assyrian Empire in Contact with the World
Authors: Novotny Jamie
Published: March 2023

This chapter discusses the history of the Assyrian Empire between the ninth and seventh centuries bc, principally through the lens of Assyria’s contacts with its contemporaries. In addition to providing a brief overview of the primary source material—in particular royal inscriptions and correspondence, two genres of texts that record some details about Assyria’s numerous interactions with the outside world—this contribution examines certain key events in order to highlight the empire’s complex relationship with its neighbors, rivals, and allies. These include Ashurnasirpal II’s lavish festivities that inaugurated his newly constructed palace and capital at Kalhu; the Battle of Qarqar between Shalmaneser III and a coalition of twelve Levantine kings; Esarhaddon’s public nomination of his royal successors on the thrones of Assyria and Babylon; the “brother war” between Ashurbanipal and Šamaš-šumu-ukin; and the fall of Assyria. The chapter also addresses external influences on Assyria, in particular the incorporation of Anatolian architectural features into Assyrian royal residences; Babylon’s function as a model for Sargon II’s new capital Dur-Šarrukin; and that city’s influence on the cult and temple of the god Aššur during the reign of Sennacherib.
The Persian Empire under the Teispid Dynasty
Authors: Waters Matt
Published: March 2023

Cyrus the Great founded the Persian Empire in roughly 550 bc. His conquests of the kingdoms of the Medes, Lydians, Babylonians, and others by the time of his death in 530 bc made this state the most expansive and durable empire until Roman times. His impact as a transformational figure in world history remains to be fully appreciated. The disparate but sporadic evidence for the period testifies to an underlying Elamite-Iranian acculturation that was formative to the rise of Cyrus’s predecessors, the Teispid dynasty, in Fars (Parsa). After the reigns of Cyrus’s sons Cambyses and Bardiya, Darius I joined Cyrus’s line to his own through marriages to Cyrus’s daughters, Atossa and Artystone. These women were important historical figures in their own right, as manifest not only in the Greek traditions but also, and primarily, in the Persepolis Fortification Archive.
The Satrapies of the Persian Empire
Authors: Bedford Peter R.
Published: March 2023

According to Herodotus, the Levant and Cyprus constituted the “fifth satrapy” of the Persian Empire, known as Ebir-nari, “Across-the-River,” in Akkadian texts. This chapter discusses the region of Across-the-River, briefly examining its constituent districts and comparing the urbanism, population density, and economic activity on the Levantine coast with less developed inland territories. The chapter also reviews aspects of the administration of Across-the-River, including evidence for the history of satrapal leadership, the various forms of sub-provincial organization, the role of Phoenician cities in Persian imperial politics, tribute/taxes and their collection, lower-level bureaucrats, the administration of law, and the place of Judah (Yehud) among sub-provinces in the southern Levant.
The Persian Empire in Contact with the World
Authors: Rollinger Robert
Published: March 2023

The chapter argues that the Persian Empire became the center of an entangled Afro-Asian world and offered one of the very first conceptions of the world as being diverse and variegated. This concept of diversity was consciously and officially propagated. It was not inserted into a dichotomized world view of “we” and “they,” “inside” and “outside,” but was equated with the world as such, a diversified world ruled by the Persian king. Moreover, the Persian Empire introduced a novel conception of empire that was both self-contained and universalistic at the same time. From an outside perspective, the concept was self-contained since it defined an imperial space that pretended to represent the world but evidently did not match this claim. From an official, interior perspective, the concept was universalistic since it professed to constitute the world, but less obviously did not reflect “reality.” The dynamic between these two concepts became especially manifest in imperial border zones that created a hotbed for specific developments of adaptations and adoptions but also propelled processes of delimitation and alienation, identity-shaping, and binary worldviews. The Persian Empire’s reach into an outside world far beyond its rulers’ direct control was the essential trigger and ingredient for these dynamic developments. Contacts and transfers were intense throughout the empire’s entire existence, pushing forward integration as well as disintegration.
After the Prophet
Authors: Matthiesen Toby
Published: March 2023

This chapter discusses the aftermath of Prophet Muhammad’s death. It notes how the sources for the early period of Islam were contested on whether it was based on Muhammad’s life and the immediate aftermath. While Muslim scholars working within the Islamic tradition do not necessarily share similar scepticism, everyone still acknowledges that early history is significant because Muslims structured their life according to the precedents set by the Prophet and his Companions (for Sunnis), and the Prophet and the Imams (for Shia). The chapter explains that the problematic nature of the sources doubts the linear narratives of the Umayyad period (661–750). It then elaborates on the divide between Sunnism and Shiism.
The Religion of Martyrdom
Authors: Matthiesen Toby
Published: March 2023

This chapter looks into the reformulation towards a religion of protest and mass mobilisation. The reformulation involved activist clerics and lay intellectuals from across the Shii worlds, and an appropriation of ideas from Marxism and Sunni Islamism. The Shi experience was one of marginality fit for lamentation and quiet survival instead of political rule. Moreover, Shii history was reinterpreted and formed the basis of an activist Shii ideology. The chapter explains how Iran tried to be accepted by Sunnis but relied heavily on Shii symbolism. It cites that the aspect of self-sacrifice and the iconography of activist Shiism became propaganda tools in a major war effort, and influenced global Shiism.
What does God know?
Authors: Jong Jonathan
Published: March 2023

This chapter takes us to the Tyva Republic, in Southern Siberia. The gods there are said to be broadly unconcerned with human moral behavior; they are even said by Tuvans to be morally indifferent. But Ben Purzycki wondered if they genuinely believed that. So, he went out there, bringing with him a combination tools, including questionnaires, response time measures, and vignettes. What he discovers is that local deities are much more like so-called “big gods” than scholars assume: they too both know and care about human shenanigans. This research is a good example of a recent development in the social sciences that combines quantitative research methods from psychology with the deep fieldwork characteristic of anthropology.
Role Obligations to Alter Role Obligations
Authors: Collins Stephanie
Published: March 2023

Many roles are situated within organizations. The occupants of these roles often confront a dilemma between (i) the occupancy conditions, performance conditions, and functions of the role, as bestowed upon the role by the organization’s decision-making procedures, and (ii) the occupancy conditions, performance conditions, and function that the role should ideally have. This chapter argues that this dilemma should be resolved in favour of (ii). Yet this does not require forgoing role-based considerations in favour of extra-role considerations. Instead, we should conceptualize organizationally specified roles as being one token of an underlying role-type. The underlying role-type provides the organizational role-token with its fundamental occupancy conditions, performance conditions, and function. When the token is a poor instance of its type, organizational role-occupants have obligations—grounded in the fundamental aspects of the role—to challenge this. These are role obligations that call upon one to alter one’s role obligations.
Two-dimensional spectroscopy of semiconductor quantum dots
Authors: Li Hebin , Lomsadze Bachana , Moody Galan , Smallwood Christopher L. , Cundiff Steven T.
Published: March 2023

Two-dimensional spectroscopy of a variety of semiconductor quantum dots is discussed in this chapter. The chapter begins with the optical and electronic properties of quantum dots. Experiments on three specific types of quantum dots are discussed, including GaAs interfacial fluctuation dots, self-assembled In(Ga)As dots including coherent control experiments, and colloidal dots.
Introduction
Authors: Chadha Monima
Published: March 2023

This book sets forth a revisionary conceptual scheme envisaged by the ancient Indian Buddhist philosopher Vasubandhu. The book describes his revisionary no-self and no-person metaphysics and its normative implications as an alternative vantage point to challenge what we ordinarily assume and intuit. I argue that we can account for the phenomenology and the subjective character of our ordinary conscious experience in the absence of selves and persons. The no-person view, however, leaves us without a basis for our person-related concerns and interpersonal practices. A wholesale rejection of our ordinary practices is practically impossible. The best way forward is to build theories of “what we are” and “how we should live” that are mutually constrained by some forms of reflective equilibrium.
Historical Introduction to Abhidharma Buddhist Philosophy
Authors: Chadha Monima
Published: March 2023

The scene is set with placing Abhidharma philosophy in the context of the history of Buddhism followed by a short introduction to the Abhidharma tradition mentioning some key divisions, seminal texts, and philosophers in this scholastic tradition. This is not an exhaustive list. The purpose is to give the reader a flavor of the complexity and evolution of the Abhidharma tradition and to introduce our protagonist, Vasubandhu. This is followed by a discussion of their distinctive theses and the role of meditation in Abhidharma Buddhist philosophy. The Abhidharma tradition is known for providing the first systematic account of conscious experiences without a self within the Buddhist tradition.
Self/No-Self in Abhidharma Philosophy
Authors: Chadha Monima
Published: March 2023

This chapter locates Vasubandhu’s no-self view in the contemporary landscape of the self/no-self debate. After placing the no-self view in this analytical framework, the chapter presents Vasubandhu’s argument for his claim that there is no need to posit a self because it is causally impotent. The argument reveals Vasubandhu’s strategy which is to show that different components of the “mental” do all the causal work. He also argues against persons using the same strategy. In order to be true to the spirit and argumentative strategy employed by Vasubandhu we should reject selves and persons. Vasubandhu would not approve of positing conventional persons to do the work of the self.