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BACKGROUND AND PURPOSE: 3', 5'-cyclic adenosine monophosphate (cAMP) is a central second messenger that broadly regulates cell function and can underpin pathophysiology. In chronic obstructive pulmonary disease (COPD), a lung disease primarily provoked by cigarette smoke (CS), the induction of cAMP-dependent pathways, via inhibition of hydrolyzing phosphodiesterases (PDEs), is a prime therapeutic strategy. Mechanisms that disrupt cAMP signaling in airway cells, in particular regulation of endogenous PDEs are poorly understood.EXPERIMENTAL APPROACH: We used a novel Förster resonance energy transfer (FRET) based cAMP biosensor in mouse in vivo, ex vivo precision cut lung slices (PCLS), and in human in vitro cell models to track the effects of CS exposure.KEY RESULTS: Under fenoterol stimulated conditions, FRET responses to cilostamide were significantly increased in in vivo, ex vivo PCLS exposed to CS and in human airway smooth muscle cells exposed to CS extract. FRET signals to rolipram were only increased in the in vivo CS model. Under basal conditions, FRET responses to cilostamide and rolipram were significantly increased in in vivo, ex vivo PCLS exposed to CS. Elevated FRET signals to rolipram correlated with a protein upregulation of PDE4 subtypes. In ex vivo PCLS exposed to CS extract, rolipram reversed downregulation of ciliary beating frequency, whereas only cilostamide significantly increased airway relaxation of methacholine pre-contracted airways.CONCLUSION AND IMPLICATIONS: We show that CS upregulates expression and activity of both PDE3 and PDE4, which regulate real-time cAMP dynamics. These mechanisms determine the availability of cAMP and can contribute to CS-induced pulmonary pathophysiology.

Spider mites are destructive arthropod pests on many crops. The generalist herbivorous mite Tetranychus urticae induces defenses in tomato (Solanum lycopersicum) and this constrains its fitness. By contrast, the Solanaceae‐specialist Tetranychus evansi maintains a high reproductive performance by suppressing tomato defenses. Tetranychus evansi outcompetes T. urticae when infesting the same plant, but it is unknown whether this is facilitated by the defenses of the plant.We assessed the extent to which a secondary infestation by a competitor affects local plant defense responses (phytohormones and defense genes), mite gene expression and mite performance.We observed that T. evansi switches to hyper‐suppression of defenses after its tomato host is also invaded by its natural competitor T. urticae. Jasmonate (JA) and salicylate (SA) defenses were suppressed more strongly, albeit only locally at the feeding site of T. evansi, upon introduction of T. urticae to the infested leaflet. The hyper‐suppression of defenses coincided with increased expression of T. evansi genes coding for salivary defense‐suppressing effector proteins and was paralleled by an increased reproductive performance.Together, these observations suggest that T. evansi overcompensates its reproduction through hyper‐suppression of plant defenses in response to nearby competitors. We hypothesize that the competitor‐induced overcompensation promotes competitive population growth of T. evansi on tomato.

Journal of applied crystallography 53(3), 760 - 780 (2020). doi:10.1107/S1600576720005567, A method is presented for the measurement of the phase gradient of a wavefront by tracking the relative motion of speckles in projection holograms as a sample is scanned across the wavefront. By removing the need to obtain an undistorted reference image of the sample, this method is suitable for the metrology of highly divergent wavefields. Such wavefields allow for large magnification factors that, according to current imaging capabilities, will allow for nanoradian angular sensitivity and nanoscale sample projection imaging. Both the reconstruction algorithm and the imaging geometry are nearly identical to that of ptychography, except that the sample is placed downstream of the beam focus and that no coherent propagation is explicitly accounted for. Like other X-ray speckle tracking methods, it is robust to low-coherence X-ray sources, making it suitable for laboratory-based X-ray sources. Likewise, it is robust to errors in the registered sample positions, making it suitable for X-ray free-electron laser facilities, where beam-pointing fluctuations can be problematic for wavefront metrology. A modified form of the speckle tracking approximation is also presented, based on a second-order local expansion of the Fresnel integral. This result extends the validity of the speckle tracking approximation and may be useful for similar approaches in the field., Published by Wiley-Blackwell, [S.l.]

The co‐occurrence of cancer and heart failure (HF) represents a significant clinical drawback as each disease interferes with the treatment of the other. In addition to shared risk factors, a growing body of experimental and clinical evidence reveals numerous commonalities in the biology underlying both pathologies. Inflammation emerges as a common hallmark for both diseases as it contributes to the initiation and progression of both HF and cancer. Under stress, malignant and cardiac cells change their metabolic preferences to survive, which makes these metabolic derangements a great basis to develop intersection strategies and therapies to combat both diseases. Furthermore, genetic predisposition and clonal haematopoiesis are common drivers for both conditions and they hold great clinical relevance in the context of personalized medicine. Additionally, altered angiogenesis is a common hallmark for failing hearts and tumours and represents a promising substrate to target in both diseases. Cardiac cells and malignant cells interact with their surrounding environment called stroma. This interaction mediates the progression of the two pathologies and understanding the structure and function of each stromal component may pave the way for innovative therapeutic strategies and improved outcomes in patients. The interdisciplinary collaboration between cardiologists and oncologists is essential to establish unified guidelines. To this aim, pre‐clinical models that mimic the human situation, where both pathologies coexist, are needed to understand all the aspects of the bidirectional relationship between cancer and HF. Finally, adequately powered clinical studies, including patients from all ages, and men and women, with proper adjudication of both cancer and cardiovascular endpoints, are essential to accurately study these two pathologies at the same time., We describe the co‐occurrence of cancer and heart failure (HF), their potential shared risk factors, and their pathophysiological mechanisms. We advocate intense interaction between cardiologists and oncologists to achieve unifying hypotheses and collaborative pre‐clinical and clinical studies.

Journal of synchrotron radiation 27(3), 625 - 632 (2020). doi:10.1107/S1600577520002192, The unique diagnostic possibilities of X-ray diffraction, small X-ray scattering and phase-contrast imaging techniques applied with high-intensity coherent X-ray synchrotron and X-ray free-electron laser radiation can only be fully realized if a sufficient dynamic range and/or spatial resolution of the detector is available. In this work, it is demonstrated that the use of lithium fluoride (LiF) as a photoluminescence (PL) imaging detector allows measuring of an X-ray diffraction image with a dynamic range of ∼107 within the sub-micrometre spatial resolution. At the PETRA III facility, the diffraction pattern created behind a circular aperture with a diameter of 5 µm irradiated by a beam with a photon energy of 500 eV was recorded on a LiF crystal. In the diffraction pattern, the accumulated dose was varied from 1.7 × 10$^5$ J cm$^{−3}$ in the central maximum to 2 × 10$^{−2}$ J cm$^{−3}$ in the 16th maximum of diffraction fringes. The period of the last fringe was measured with 0.8 µm width. The PL response of the LiF crystal being used as a detector on the irradiation dose of 500 eV photons was evaluated. For the particular model of laser-scanning confocal microscope Carl Zeiss LSM700, used for the readout of the PL signal, the calibration dependencies on the intensity of photopumping (excitation) radiation (λ = 488 nm) and the gain have been obtained., Published by Wiley-Blackwell, [S.l.]

To assess maternal health care service utilisation and associated factors in Somali pastoral communities of eastern Ethiopia.Community-based cross-sectional study complemented by qualitative assessments in Adadle district, Somali region, eastern Ethiopia, among 450 women in six kebeles from August to September 2016. Logistic regression was used to assess factors associated with antenatal care use and skilled delivery care use, controlling for confounders.About 27% [95%CI 22.8-31.2%] of women used antenatal care, and 22.6% [95%CI 18.7-26.5%] received skilled delivery service. None of the respondents reported post-natal care. About 43% reported that they had no knowledge of antenatal care, and 46% did not perceive delivery at a health facility as important. Pastoral lifestyle, husband's educational status, women's attitude towards health care service and financial support from the husband were significantly associated with antenatal care utilisation. Health professionals' attitudes, perceptions of institutional delivery, antenatal care utilisation and information about exemptions from maternal health care fees were associated with skilled delivery service utilisation.Improving community awareness of antenatal care, employing female health professionals and culturally adapted guidelines could improve skilled delivery utilisation. In a patriarchal society, involving male partners in all maternal health issues is essential to increase use of maternal health services and to decrease maternal mortality.Evaluer l'utilisation des services de soins de santé maternelle et les facteurs associés dans les communautés pastorales somaliennes dans l'est de l'Ethiopie. MÉTHODES: Etude transversale basée sur la communauté complétée par des évaluations qualitatives dans le district d'Adadle, région somalienne, dans l'est de l'Ethiopie, portant sur 450 femmes dans six kebeles d'août à septembre 2016. Une régression logistique a été utilisée pour évaluer les facteurs associés à l'utilisation des soins prénatals et à l'accouchement sous soins qualifiés, en ajustant pour les facteurs confusionnels. RÉSULTATS: 27% [IC95%: 22.8-31.2%] des femmes ont utilisé des soins prénatals et 22,6% [IC95%: 18.7-26.5%] ont reçu des services d'accouchement qualifiés. Aucune des répondantes n'a signalé des soins postnatals. 43% ont déclaré qu'elles n'avaient aucune connaissance des soins prénatals et 46% ne percevaient pas l'accouchement dans un établissement de santé comme important. Le mode de vie pastoral, le niveau d'éducation du mari, l'attitude des femmes à l'égard des services de santé et le soutien financier du mari étaient significativement associés à l'utilisation des soins prénatals. Les attitudes des professionnels de la santé, les perceptions de l'accouchement en établissement, l'utilisation des soins prénatals et les informations sur les exemptions des frais de soins de santé maternelle ont été associées à l'utilisation des services d'accouchement qualifiés.Améliorer la sensibilisation de la communauté aux soins prénatals, employer des professionnels de la santé féminins et des directives culturellement adaptées pourrait améliorer l'utilisation de l’accouchement qualifié. Dans une société patriarcale, la participation des partenaires masculins à toutes les questions de santé maternelle est essentielle pour accroître l'utilisation des services de santé maternelle et réduire la mortalité maternelle.

Diabetes and metabolic syndrome are associated with the typical American high glycemia diet and result in accumulation of high levels of advanced glycation end products (AGEs), particularly upon aging. AGEs form when sugars or their metabolites react with proteins. Associated with a myriad of age‐related diseases, AGEs accumulate in many tissues and are cytotoxic. To date, efforts to limit glycation pharmacologically have failed in human trials. Thus, it is crucial to identify systems that remove AGEs, but such research is scanty. Here, we determined if and how AGEs might be cleared by autophagy. Our in vivo mouse and C. elegans models, in which we altered proteolysis or glycative burden, as well as experiments in five types of cells, revealed more than six criteria indicating that p62‐dependent autophagy is a conserved pathway that plays a critical role in the removal of AGEs. Activation of autophagic removal of AGEs requires p62, and blocking this pathway results in accumulation of AGEs and compromised viability. Deficiency of p62 accelerates accumulation of AGEs in soluble and insoluble fractions. p62 itself is subject to glycative inactivation and accumulates as high mass species. Accumulation of p62 in retinal pigment epithelium is reversed by switching to a lower glycemia diet. Since diminution of glycative damage is associated with reduced risk for age‐related diseases, including age‐related macular degeneration, cardiovascular disease, diabetes, Alzheimer's, and Parkinson's, discovery of methods to limit AGEs or enhance p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies., AGEs are toxic compounds formed by non‐enzymatic reactions between sugars and proteins. AGEs are prone to aggregate. Insoluble AGEs are efficiently removed via p62‐selective autophagy. The autophagic removal of AGEs is a conserved pathway, and the lack of p62 leads to accumulation of toxic AGEs in mouse and worms. Enhanced autophagy is protective against glycation‐derived damage. p62‐dependent autophagy offers novel potential therapeutic targets to treat AGEs‐related pathologies.

Journal of synchrotron radiation 27(5), 1339 - 1346 (2020). doi:10.1107/S1600577520007407, Hard X-ray nanotomography enables 3D investigations of a wide range of samples with high resolution (, Published by Wiley-Blackwell, [S.l.]

Acta crystallographica / D 75(2), 1-15 (2019). doi:10.1107/S205979831801238X, This article provides a step-by-step guide to the use of the CrystFEL software for processing serial crystallography data from an X-ray free-electron laser or a synchrotron light source. Whereas previous papers have described the theory and algorithms and their rationale, this paper describes the steps to be performed from a user perspective, including command-line examples., Published by Wiley-Blackwell, Oxford

The new phytologist 213(3), 1346-1362 (2017). doi:10.1111/nph.14220, Published by Wiley-Blackwell, Oxford [u.a.]

A comparative study on the self‐assembly of sexiphenyl‐dicarbonitrile on highly oriented pyrolytic graphite and single‐layer graphene on Cu(111) is presented. Despite an overall low molecule–substrate interaction, the close‐packed structures exhibit a peculiar shift repeating every four to five molecules. This shift has hitherto not been reported for similar systems and is hence a unique feature induced by the graphitic substrates.

The new phytologist 221(2), 881-895 (2019). doi:10.1111/nph.15442, Published by Wiley-Blackwell, Oxford [u.a.]

To obtain insights into the dynamics of nutrient exchange in arbuscular mycorrhizal (AM) symbiosis, we modelled mathematically the two‐membrane system at the plant–fungus interface and simulated its dynamics. In computational cell biology experiments, the full range of nutrient transport pathways was tested for their ability to exchange phosphorus (P)/carbon (C)/nitrogen (N) sources. As a result, we obtained a thermodynamically justified, independent and comprehensive model of the dynamics of the nutrient exchange at the plant–fungus contact zone. The predicted optimal transporter network coincides with the transporter set independently confirmed in wet‐laboratory experiments previously, indicating that all essential transporter types have been discovered. The thermodynamic analyses suggest that phosphate is released from the fungus via proton‐coupled phosphate transporters rather than anion channels. Optimal transport pathways, such as cation channels or proton‐coupled symporters, shuttle nutrients together with a positive charge across the membranes. Only in exceptional cases does electroneutral transport via diffusion facilitators appear to be plausible. The thermodynamic models presented here can be generalized and adapted to other forms of mycorrhiza and open the door for future studies combining wet‐laboratory experiments with computational simulations to obtain a deeper understanding of the investigated phenomena.

Fish oil rich in polyunsaturated omega-3 fatty acids is extracted in high yield from anchovy filleting waste using d-limonene as green biosolvent in a simple solid-liquid extraction performed by mechanically stirring and maceration followed by limonene removal via evaporation under reduced pressure. As limonene is renewably obtained from waste orange peel, this method closes the materials cycle and establishes a circular economy process to obtain high quality fish oil from biowaste available worldwide in several million t/year amount. Significant economic, social and environmental benefits are anticipated.

The solution of a structure of human Rab27a suffering from severe anisotropy and translational noncrystallographic symmetry was aided by identifying diffraction measurements with low information content., Data pathologies caused by effects such as diffraction anisotropy and translational noncrystallographic symmetry (tNCS) can dramatically complicate the solution of the crystal structures of macromolecules. Such problems were encountered in determining the structure of a mutant form of Rab27a, a member of the Rab GTPases. Mutant Rab27a constructs that crystallize in the free form were designed for use in the discovery of drugs to reduce primary tumour invasiveness and metastasis. One construct, hRab27aMut, crystallized within 24 h and diffracted to 2.82 Å resolution, with a unit cell possessing room for a large number of protein copies. Initial efforts to solve the structure using molecular replacement by Phaser were not successful. Analysis of the data set revealed that the crystals suffered from both extreme anisotropy and strong tNCS. As a result, large numbers of reflections had estimated standard deviations that were much larger than their measured intensities and their expected intensities, revealing problems with the use of such data at the time in Phaser. By eliminating extremely weak reflections with the largest combined effects of anisotropy and tNCS, these problems could be avoided, allowing a molecular-replacement solution to be found. The lessons that were learned in solving this structure have guided improvements in the numerical analysis used in Phaser, particularly in identifying diffraction measurements that convey very little information content. The calculation of information content could also be applied as an alternative to ellipsoidal truncation. The post-mortem analysis also revealed an oversight in accounting for measurement errors in the fast rotation function. While the crystal of mutant Rab27a is not amenable to drug screening, the structure can guide new modifications to obtain more suitable crystal forms.

Journal of synchrotron radiation 26(4), 1092 - 1100 (2019). doi:10.1107/S1600577519005174, A novel X-ray gas monitor (XGM) has been developed which allows the measurement of absolute photon pulse energy and photon beam position at all existing and upcoming free-electron lasers (FELs) over a broad spectral range covering vacuum ultraviolet (VUV), extreme ultraviolet (EUV) and soft and hard X-rays. The XGM covers a wide dynamic range from spontaneous undulator radiation to FEL radiation and provides a temporal resolution of better than 200 ns. The XGM consists of two X-ray gas-monitor detectors (XGMDs) and two huge-aperture open electron multipliers (HAMPs). The HAMP enhances the detection efficiency of the XGM for low-intensity radiation down to 10$^5$ photons per pulse and for FEL radiation in the hard X-ray spectral range, while the XGMD operates in higher-intensity regimes. The relative standard uncertainty for measurements of the absolute photon pulse energy is well below 10%, and down to 1% for measurements of relative pulse-to-pulse intensity on pulses with more than 10$^{10}$ photons per pulse. The accuracy of beam-position monitoring in the vertical and horizontal directions is of the order of 10 µm., Published by Wiley-Blackwell, Chester

A multimodal in situ nanofocused X-ray microscopy approach is demonstrated and applied to a working polycrystalline thin film solar cell that revealed chemical, structural and electronic heterogeneity from a single measurement., The factors limiting the performance of alternative polycrystalline solar cells as compared with their single-crystal counterparts are not fully understood, but are thought to originate from structural and chemical heterogeneities at various length scales. Here, it is demonstrated that multimodal focused nanobeam X-ray microscopy can be used to reveal multiple aspects of the problem in a single measurement by mapping chemical makeup, lattice structure and charge collection efficiency simultaneously in a working solar cell. This approach was applied to micrometre-sized individual grains in a Cu(In,Ga)Se2 polycrystalline film packaged in a working device. It was found that, near grain boundaries, collection efficiency is increased, and that in these regions the lattice parameter of the material is expanded. These observations are discussed in terms of possible physical models and future experiments.

Journal of applied crystallography 52(5), 1144 - 1156 (2019). doi:10.1107/S1600576719010720, Single-crystal elastic constants have been derived by lattice strain measurements using neutron diffraction on polycrystalline Ti-6Al-4V, Ti-6Al-2Sn-4Zr-6Mo and Ti-3Al-8V-6Cr-4Zr-4Mo alloy samples. A variety of model approximations for the grain-to-grain interactions, namely approaches by Voigt, Reuss, Hill, Kroener, de Wit and Matthies, including texture weightings, have been applied and compared. A load-transfer approach for multiphase alloys was also implemented and the results are compared with single-phase data. For the materials under investigation, the results for multiphase alloys agree well with the results for single-phase materials in the corresponding phases. In this respect, all eight elastic constants in the dual-phase Ti-6Al-2Sn-4Zr-6Mo alloy have been derived for the first time., Published by Wiley-Blackwell, [S.l.]

Methods for efficient data extraction for neutron spin-echo spectroscopy with multipixel area detectors and – at a pulsed neutron source – multiple time-of-flight wavelength bins are presented., Neutron spin-echo spectrometers with a position-sensitive detector and operating with extended time-of-flight-tagged wavelength frames are able to collect a comprehensive set of data covering a large range of wavevector and Fourier time space with only a few instrumental settings in a quasi-continuous way. Extracting all the information contained in the raw data and mapping them to a suitable physical space in the most efficient way is a challenge. This article reports algorithms employed in dedicated software, DrSpine (data reduction for spin echo), that achieves this goal and yields reliable representations of the intermediate scattering function S(Q, t) independent of the selected ‘binning’.

An indirect Fourier transform/simulated annealing method exploits the information content of multiple solvent contrast neutron reflectivity data and permits the model-independent recovery of interfacial structure at the air/liquid and solid/liquid interface., Neutron specular reflectivity at soft interfaces provides sub-nanometre information concerning the molecular distribution of thin films, while the application of contrast variation can highlight the scattering from different parts of the system and lead to an overall reduction in fitting ambiguity. Traditional modelling approaches involve the construction of a trial scattering length density profile based on initial speculation and the subsequent refinement of its parameters through minimization of the discrepancy between the calculated and measured reflectivity. In practice this might produce an artificial bias towards specific sets of solutions. On the other hand, direct inversion of reflectivity data, despite its ability to provide a unique solution, is subject to limitations and experimental complications. Presented here is an integrated indirect Fourier transform/simulated annealing method that, when applied to multiple solvent contrast reflectivity data and within the limits of finite spatial resolution, leads to reliable reconstructions of the interfacial structure without the need for any a priori assumptions. The generality of the method permits its straightforward application in common experimental contrast-variation investigations at the solid/liquid and air/liquid interface.

Choosing the optimal catalyst for a new transformation is challenging because the ideal molecular requirements of the catalyst for one reaction do not always simply translate to another. Large groups at the 3,3′ positions of the binaphthol rings are important for efficient stereoinduction but if they are too large this can lead to unusual or poor results. By applying a quantitative steric assessment of the substituents at the 3,3′ positions of the binaphthol ring, we have systematically studied the effect of modulating this group on enantioselectivity for a wide range of reactions involving imines, and verified this analysis using ONIOM calculations. We have shown that in most reactions, the stereochemical outcome depends on both proximal and remote sterics. Summarising detailed calculations into a simple qualitative model identifies and explains the steric features required for high selectivity. This model is consistent with seventy seven papers reporting reactions (over 1000 transformations in total), and provides a straightforward decision tree for selecting the best catalyst.

The ubiquitin-like modifier (UBL) SUMO (Small Ubiquitin-Like Modifier) regulates protein function. Structural rather than sequence homology typifies UBL families. However, individual UBL types, such as SUMO, show remarkable sequence conservation. Selection pressure also operates at the SUMO gene copy number, as increased SUMO levels activate immunity and alter flowering time in Arabidopsis. We show how, despite this selection pressure, the SUMO family has diversified into eight paralogues in Arabidopsis. Relationships between the paralogues were investigated using genome collinearity and gene tree analysis. We show that palaeopolyploidy followed by tandem duplications allowed expansion and then diversification of the SUMO genes. For example, Arabidopsis SUMO5 evolved from the pan-eudicot palaeohexaploidy event (gamma), which yielded three SUMO copies. Two gamma copies were preserved as archetype SUMOs, suggesting subfunctionalization, whereas the third copy served as a hotspot for SUMO diversification. The Brassicaceae-specific alpha duplication then caused the duplication of one archetype gamma copy, which, by subfunctionalization, allowed the retention of both SUMO1 and SUMO2. The other archetype gamma copy was simultaneously pseudogenized (SUMO4/6). A tandem duplication of SUMO2 subsequently yielded SUMO3 in the Brassicaceae crown group. SUMO3 potentially neofunctionalized in Arabidopsis, but it is lost in many Brassicaceae. Our advanced methodology allows the study of the birth and fixation of other paralogues in plants.

Parents tend to modulate their movements when demonstrating actions to their infants. Thus far, these modulations have primarily been quantified by human raters and for entire interactions, thereby possibly overlooking the intricacy of such demonstrations. Using optical motion tracking, the precise modulations of parents’ infant‐directed actions were quantified and compared to adult‐directed actions and between action types. Parents demonstrated four novel objects to their 14‐month‐old infants and adult confederates. Each object required a specific action to produce a unique effect (e.g. rattling). Parents were asked to demonstrate an object at least once before passing it to their demonstration partner, and they were subsequently free to exchange the object as often as desired. Infants’ success at producing the objects’ action‐effects was coded during the demonstration session and their memory of the action‐effects was tested after a several‐minute delay. Indicating general modulations across actions, parents repeated demonstrations more often, performed the actions in closer proximity and demonstrated action‐effects for longer when interacting with their infant compared to the adults. Meanwhile, modulations of movement size and velocity were specific to certain action‐effect pairs. Furthermore, a ‘just right’ modulation of proximity was detected, since infants’ learning, memory, and parents’ prior evaluations of their infants’ motor abilities, were related to demonstrations that were performed neither too far from nor too close to the infants. Together, these findings indicate that infant‐directed action modulations are not solely overall exaggerations but are dependent upon the characteristics of the to‐be learned actions, their effects, and the infant learners., Parents’ infant‐ and adult‐directed demonstrations of four novel objects with opaque action‐effects were recorded using optical motion tracking. For all objects, parents demonstrated actions closer (i.e. higher proximity) and showed effects longer when interacting with their infants compared to adult partners. Additionally, auditory‐effect actions were performed more slowly, and for two of the actions parents made larger movements for their infants than for adults.

Inbreeding depression is widely hypothesised to drive adaptive evolution of pre-copulatory and post-copulatory mechanisms of inbreeding avoidance, which in turn are hypothesised to affect evolution of polyandry (i.e., female multiple mating). However, surprisingly little theory or modelling critically examines selection for pre-copulatory or post-copulatory inbreeding avoidance, or both strategies, given evolutionary constraints and direct costs, or examines how evolution of inbreeding avoidance strategies might feed back to affect evolution of polyandry. Selection for post-copulatory inbreeding avoidance, but not for pre-copulatory inbreeding avoidance, requires polyandry, while interactions between pre-copulatory and post-copulatory inbreeding avoidance might cause functional redundancy (i.e., ‘degeneracy’) potentially generating complex evolutionary dynamics among inbreeding strategies and polyandry. We used individual-based modelling to quantify evolution of interacting pre-copulatory and post-copulatory inbreeding avoidance and associated polyandry given strong inbreeding depression and different evolutionary constraints and direct costs. We found that evolution of post-copulatory inbreeding avoidance increased selection for initially rare polyandry, and that evolution of a costly inbreeding avoidance strategy became negligible over time given a lower cost alternative strategy. Further, fixed pre-copulatory inbreeding avoidance often completely precluded evolution of polyandry and hence post-copulatory inbreeding avoidance, but fixed post-copulatory inbreeding avoidance did not preclude evolution of pre-copulatory inbreeding avoidance. Evolution of inbreeding avoidance phenotypes and associated polyandry are therefore affected by evolutionary feedbacks and degeneracy. All else being equal, evolution of pre-copulatory inbreeding avoidance and resulting low polyandry is more likely when post-copulatory inbreeding avoidance is precluded or costly, and evolution of post-copulatory inbreeding avoidance greatly facilitates evolution of costly polyandry.

In stratified epithelia such as the epidermis, homeostasis is maintained by the proliferation of cells in the lower epithelial layers and the concomitant loss of differentiated cells from the epithelial surface. These differentiating keratinocytes progressively stratify and form a self‐regenerating multi‐layered barrier that protects the underlying dermis. In such tissue, the continual loss and replacement of differentiated cells also limits the accumulation of oncogenic mutations within the tissue. Inactivating mutations in key driver genes, such as TP53 and NOTCH1, reduce the proportion of differentiating cells allowing for the long‐term persistence of expanding mutant clones in the tissue. Here we show that through the expression of E6, HPV‐16 prevents the early fate commitment of human keratinocytes towards differentiation and confers a strong growth advantage to human keratinocytes. When E6 is expressed either alone or with E7, it promotes keratinocyte proliferation at high cell densities, through the combined inactivation of p53 and Notch1. In organotypic raft culture, the activity of E6 is restricted to the basal layer of the epithelium and is enhanced during the progression from productive to abortive or transforming HPV‐16 infection. Consistent with this, the expression of p53 and cleaved Notch1 becomes progressively more disrupted, and is associated with increased basal cell density and reduced commitment to differentiation. The expression of cleaved Notch1 is similarly disrupted also in HPV‐16‐positive cervical lesions, depending on neoplastic grade. When taken together, these data depict an important role of high‐risk E6 in promoting the persistence of infected keratinocytes in the basal and parabasal layers through the inactivation of gene products that are commonly mutated in non‐HPV‐associated neoplastic squamous epithelia. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Background and Purpose: Endothelin-1 (ET-1) reduces insulin-stimulated glucose uptake in skeletal muscle, inducing insulin resistance. Here, we have determined the molecular mechanisms underlying negative regulation by ET-1 of insulin signalling. Experimental Approach: We used the rat L6 skeletal muscle cells fully differentiated into myotubes. Changes in the phosphorylation of Akt was assessed by Western blotting. Effects of ET-1 on insulin-stimulated glucose uptake was assessed with [3H]-2-deoxy-d-glucose ([3H]2-DG). The C-terminus region of GPCR kinase 2 (GRK2-ct), a dominant negative GRK2, was overexpressed in L6 cells using adenovirus-mediated gene transfer. GRK2 expression was suppressed by transfection of the corresponding short-interfering RNA (siRNA). Key Results: In L6 myotubes, insulin elicited sustained Akt phosphorylation at Thr308 and Ser473, which was suppressed by ET-1. The inhibitory effects of ET-1 were prevented by treatment with a selective ETA receptor antagonist and a Gq protein inhibitor, overexpression of GRK2-ct and knockdown of GRK2. Insulin increased [3H]2-DG uptake rate in a concentration-dependent manner. ET-1 noncompetitively antagonized insulin-stimulated [3H]2-DG uptake. Blockade of ETA receptors, overexpression of GRK2-ct and knockdown of GRK2 prevented the ET-1-induced suppression of insulin-stimulated [3H]2-DG uptake. In L6 myotubes overexpressing FLAG-tagged GRK2, ET-1 facilitated the interaction of endogenous Akt with FLAG-GRK2. Conclusions and Implications: Activation of ETA receptors with ET-1 suppressed insulin-induced Akt phosphorylation at Thr308 and Ser473 and [3H]2-DG uptake in a GRK2-dependent manner in skeletal muscle cells. These findings suggest that ETA receptors and GRK2 are potential targets for overcoming insulin resistance.

Background: Sublingual immunotherapy (SLIT) is a potential efficacious and safe treatment option for patients with respiratory, IgE-mediated allergic diseases. A combined tolerability, dose-finding study with a sublingual liquid birch pollen preparation (SB) was conducted.Methods: Two hundred and sixty-nine adults with birch-pollen-induced AR were randomized to placebo, SB: 3333, 10 000, 20 000 or 40 000 AUN/ml. Differences in symptom scores following a titrated nasal provocation test (TNPT) at baseline and after 5 months of treatment were determined. Safety, tolerability, birch-pollen- specific immunoglobulin levels and peak nasal inspiratory flow (PNIF) were also measured (all measures determined outside the birch pollen season).Results: In all treatment groups, an improvement in symptom scores after treatment compared to baseline was observed, with an additional stepwise improvement in the active groups compared to placebo, which was significant in high-dose groups (P = 0.008 and P Conclusions: A multicentre trial evaluated the dose-response and tolerability of SB. All active treatment groups showed better responses than placebo for both primary and secondary parameters. The results indicate that, within the studied dose range, SB 40 000 AUN/ml is the most optimal effective and safe dose (ClinicalTrials.gov: NCT01639768).

Crystallographic methods are used to identify the primary mineral phase of pseudomorphs of crystals embedded in 3.48 Ga bedded carbonate-chert rocks from the Dresser Formation, Pilbara Craton, Australia. This identification provides valuable information on the chemical environments at the onset of life on Earth., Crystallography has a long history of providing knowledge and methods for applications in other disciplines. The identification of minerals using X-ray diffraction is one of the most important contributions of crystallography to earth sciences. However, when the crystal itself has been dissolved, replaced or deeply modified during the geological history of the rocks, diffraction information is not available. Instead, the morphology of the crystal cast provides the only crystallographic information on the original mineral phase and the environment of crystal growth. This article reports an investigation of crystal pseudomorphs and crystal casts found in a carbonate-chert facies from the 3.48 Ga-old Dresser Formation (Pilbara Craton, Australia), considered to host some of the oldest remnants of life. A combination of X-ray microtomography, energy-dispersive X-ray spectroscopy and crystallographic methods has been used to reveal the original phases of these Archean pseudomorphs. It is found with a high degree of confidence that the original crystals forming in Archean times were hollow aragonite, the high-temperature polymorphs of calcium carbonate, rather than other possible alternatives such as gypsum (CaSO4·2H20) and nahcolite (NaHCO3). The methodology used is described in detail.

Acta crystallographica / D 74(8), 727 - 738 (2018). doi:10.1107/S2059798318005004, Biological small-angle X-ray solution scattering (BioSAXS) is now widely used to gain information on biomolecules in the solution state. Often, however, it is not obvious in advance whether a particular sample will scatter strongly enough to give useful data to draw conclusions under practically achievable solution conditions. Conformational changes that appear to be large may not always produce scattering curves that are distinguishable from each other at realistic concentrations and exposure times. Emerging technologies such as time-resolved SAXS (TR-SAXS) pose additional challenges owing to small beams and short sample path lengths. Beamline optics vary in brilliance and degree of background scatter, and major upgrades and improvements to sources promise to expand the reach of these methods. Computations are developed to estimate BioSAXS sample intensity at a more detailed level than previous approaches, taking into account flux, energy, sample thickness, window material, instrumental background, detector efficiency, solution conditions and other parameters. The results are validated with calibrated experiments using standard proteins on four different beamlines with various fluxes, energies and configurations. The ability of BioSAXS to statistically distinguish a variety of conformational movements under continuous-flow time-resolved conditions is then computed on a set of matched structure pairs drawn from the Database of Macromolecular Motions (http://molmovdb.org). The feasibility of experiments is ranked according to sample consumption, a quantity that varies by over two orders of magnitude for the set of structures. In addition to photon flux, the calculations suggest that window scattering and choice of wavelength are also important factors given the short sample path lengths common in such setups., Published by Wiley-Blackwell, Oxford

Background: Patient-reported outcome measures (PROMs) are increasingly used to establish the value of health care. In order to reflect value, PROMs should measure outcomes that matter to patients. However, patients are not always involved in the development of PROMs. This study therefore aimed to investigate whether PROMs, which were developed without patient involvement, are relevant to patients and whether the level of importance allocated towards aspects of these PROMs varies between patient groups.Methods: All patients from 20 Dutch hospitals undergoing hip or knee surgery in 2014 were invited to a PROMs survey. Participants were asked to rate the importance of each of the items in the HOOS-Physical Function Short form or the KOOS-Physical Function Short form, the EQ-5D and the NRS pain.Results: Most outcomes were considered important. However, 77.7% of hip surgery patients rated being able to run as unimportant. Being able to kneel (32.7%) or squat (39.6%) was not important to a considerable minority of knee surgery patients. Pain, especially during rest, was considered very important by both hip (68.2%) and knee (66.5%) surgery patients. Patients who were older, male, experienced overall bad health and psychological health considered many items from the PROMs less important than other patients.Discussion: Patients differ in what they consider important. Health-care professionals should explore patients’ preferences and discuss which treatment options best fit patients’ preferences. Additionally, if PROMs are used in performance measurement, further research is needed to look at whether and how variation in patient preferences can be taken into account.KEYWORDShip and knee surgery, importance ratings, patient preferences, patient-reported outcome measures

Drawing on 17 months of ethnographic fieldwork in the Netherlands and Ghana, this paper combines 'return' mobilities literature and youth studies to analyse the role of leisure practices during 'homeland' visits in transnational youth's way of relating to Ghana when they are entering into adulthood. Using the notion of mobility trajectories, the paper shows that leisure practices facilitate young people's ability to establish and renew intimate transnational relationships with diasporic friends, and Ghana-based same-generation relatives and romantic partners. Differing from earlier stays in Ghana, young people expressed their emerging sense of independence by exploring alternative sides of the country with these peers, based on common interests and belonging to the same life-cycle cohort. The findings add complexity to the notion of the 'homeland' as a monolithic place of reconnecting with family and roots by drawing attention to the intersection between young people's pathways to adulthood and transnational mobility.

Most cancers arise in old individuals, which also accumulate senescent cells. Cellular senescence can be experimentally induced by expression of oncogenes or telomere shortening during serial passage in culture. In vivo, precursor lesions of several cancer types accumulate senescent cells, which are thought to represent a barrier to malignant progression and a response to the aberrant activation of growth signaling pathways by oncogenes (oncogene toxicity). Here, we sought to define gene expression changes associated with cells that bypass senescence induced by oncogenic RAS. In the context of pancreatic ductal adenocarcinoma (PDAC), oncogenic KRAS induces benign pancreatic intraepithelial neoplasias (PanINs), which exhibit features of oncogene‐induced senescence. We found that the bypass of senescence in PanINs leads to malignant PDAC cells characterized by gene signatures of epithelial‐mesenchymal transition, stem cells, and mitochondria. Stem cell properties were similarly acquired in PanIN cells treated with LPS, and in primary fibroblasts and mammary epithelial cells that bypassed Ras‐induced senescence after reduction of ERK signaling. Intriguingly, maintenance of cells that circumvented senescence and acquired stem cell properties was blocked by metformin, an inhibitor of complex I of the electron transport chain or depletion of STAT3, a protein required for mitochondrial functions and stemness. Thus, our studies link bypass of senescence in premalignant lesions to loss of differentiation, acquisition of stemness features, and increased reliance on mitochondrial functions.

We are today increasingly experiencing the city through interfaces of platforms like Google Maps, Instagram, TripAdvisor, Airbnb, and Yelp. As our very sense of the city is shaped by these technological interfaces, the media are acquiring a constitutive role in reshaping contemporary urbanity. To conceptualize how media represent urban change, this paper draws on media studies and particularly the concept of “mediatization.” The paper studies the changing media representations of the gentrification of Rio de Janeiro’s favela Vidigal over fifteen years across different media. Using computational methods and interpretative analysis, we find that global media representations represented Vidigal as a site for adventure and investment. However, the media representations are far from monolithic. At one moment, they mobilize cosmopolitan fascination with the “other,” promoting slum tourism gentrification. At the next, they amplify critiques of gentrification and local protests against displacement. We argue that media representations are driven by their own variegated forces and cultures, which are increasingly coming to shape the dynamics of urban imaginaries.

Acta crystallographica / D 73(7), 581 - 590(2017). doi:10.1107/S2059798317006970, Cadmium ions can be effectively used to promote crystal growth and for experimental phasing. Here, the use of cadmium ions as a suitable anomalous scatterer at the standard wavelength of 1 Å is demonstrated. The structures of three different proteins were determined using cadmium single-wavelength anomalous dispersion (SAD) phasing. Owing to the strong anomalous signal, the structure of lysozyme could be automatically phased and built using a very low anomalous multiplicity (1.1) and low-completeness (77%) data set. Additionally, it is shown that cadmium ions can easily substitute divalent ions in ATP–divalent cation complexes. This property could be generally applied for phasing experiments of a wide range of nucleotide-binding proteins. Improvements in crystal growth and quality, good anomalous signal at standard wavelengths (i.e. no need to change photon energy) and rapid phasing and refinement using a single data set are benefits that should allow cadmium ions to be widely used for experimental phasing., Published by Wiley-Blackwell, Oxford

Synchrotron radiation nanotomography has been used to quantify the packing fraction in a photonic glass sample., Photonic glass is a material class that can be used as photonic broadband reflectors, for example in the infrared regime as thermal barrier coating films. Photonic properties such as the reflectivity depend on the ordering and material packing fraction over the complete film thickness of up to 100 µm. Nanotomography allows acquiring these key parameters throughout the sample volume at the required resolution in a non-destructive way. By performing a nanotomography measurement at the PETRA III beamline P05 on a photonic glass film, the packing fraction throughout the complete sample thickness was analyzed. The results showed a packing fraction significantly smaller than the expected random close packing giving important information for improving the fabrication and processing methods of photonic glass material in the future.

Background and purpose: The antidysrhythmic bretylium is useful experimentally because it selectively abolishes neurotransmitter release from sympathetic peripheral nerve terminals. Its mechanism of action seemed settled, but recent results from optical monitoring of single terminals now suggests a new interpretation. Experimental approach: Orthograde transport of a dextran-conjugated Ca2+ indicator to monitor Ca2+ in nerve terminals of mouse isolated vas deferens with a confocal microscope. In some experiments, local neurotransmitter release was detected by monitoring neuroeffector Ca2+ transients (NCTs) in adjacent smooth muscles, a local measure of purinergic transmission. Sympathetic terminals were identified with catecholamine fluorescence (UV excitation) or post-experiment immunohistochemistry. Key results: Bretylium (10 m) abolished NCTs at 60/61 junctions over the course of 2 h, indicating effective abolition of neurotransmitter release. However, bretylium did not abolish the field stimulus-induced Ca2+ transient in most nerve terminals, but did increase both action potential delay (by 20.4 ms) and absolute refractory period (by 42 ms). Immunohistochemistry demonstrated that 85–96% of terminals orthogradely filled with a dextran-conjugated fluorescent probe contained Neuropeptide Y (NPY). A formaldehyde–glutaraldehyde-induced catecholamine fluorescence (FAGLU) technique was modified to allow sympathetic terminals to be identified with a Ca2+ indicator present. Most terminals contained catecholamines (based on FAGLU) or secrete ATP (as NCTs in adjacent smooth muscle cells are abolished). Conclusions and implications: Bretylium can inhibit neurotransmitter release downstream of Ca2+ influx without abolishing the nerve terminal action potential. Bretylium-induced increases in the absolute refractory period permit living sympathetic terminals to be identified.

The structure of a bacterial M14-family carboxypeptidase determined exploiting microfocus synchrotron radiation and highly automated refinement protocols reveals its potential to act as a polyglutamylase., A potential cytosolic metallocarboxypeptidase from Burk­holderia cenocepacia has been crystallized and a synchrotron-radiation microfocus beamline allowed the acquisition of diffraction data to 1.9 Å resolution. The asymmetric unit comprises a tetramer containing over 1500 amino acids, and the high-throughput automated protocols embedded in PDB_REDO were coupled with model–map inspections in refinement. This approach has highlighted the value of such protocols for efficient analyses. The subunit is constructed from two domains. The N-terminal domain has previously only been observed in cytosolic carboxypeptidase (CCP) proteins. The C-terminal domain, which carries the Zn2+-containing active site, serves to classify this protein as a member of the M14D subfamily of carboxypeptidases. Although eukaryotic CCPs possess deglutamylase activity and are implicated in processing modified tubulin, the function and substrates of the bacterial family members remain unknown. The B. cenocepacia protein did not display deglutamylase activity towards a furylacryloyl glutamate derivative, a potential substrate. Residues previously shown to coordinate the divalent cation and that contribute to peptide-bond cleavage in related enzymes such as bovine carboxypeptidase are conserved. The location of a conserved basic patch in the active site adjacent to the catalytic Zn2+, where an acetate ion is identified, suggests recognition of the carboxy-terminus in a similar fashion to other carboxypeptidases. However, there are significant differences that indicate the recognition of substrates with different properties. Of note is the presence of a lysine in the S1′ recognition subsite that suggests specificity towards an acidic substrate.

The right to contest automated decisions as provided by Article 22 of the General Data Protection Regulation (GDPR) is a due process provision with concrete transparency implications. Based on this, the paper in hand aims, first, to provide an interpretation of Art 22 and the right to contest (as the key provision in determining the contours of transparency in relation to automated decisions under the GDPR); second, to provide a systematic account of possible administrative, procedural, and technical mechanisms (transparency measures) that could be deployed for the purpose contesting automated decisions; and third, to examine the compatibility of these mechanisms with the GDPR. Following the introduction, Part II starts with an analysis of the newly enacted right to contest solely automated decisions as provided under Article 22 of the GDPR. This part identifies the right to contest in Article 22 as the core remedy, with inherent transparency requirements which are foundational for due process. Setting the right to contest as the backbone of protection against the adverse effects of solely automated decisions, Part III focuses on certain key points and provisions under the GDPR, which are described as the 1st layer (human-intelligible) transparency. This part explores to what extent “information and access” rights (Articles 13, 14, and 15) could satisfy the transparency requirements for the purposes of contestation as explained in Part II. Next, Part IV briefly identifies the limits of 1st layer transparency – explaining how technical complexity together with competition and integrity-related concerns render human-level transparency either infeasible or legally impossible. In what follows, Part V conceptualizes a 2nd layer of transparency which consists of further administrative, procedural, and technical measures (i.e., design choices facilitating interpretability, institutional oversight, and algorithmic scrutiny). Finally, Part VI identifies four regulatory options, combining 1st and 2nd layer transparency measures to implement Article 22. The primary aim of the paper is to provide a systematic interpretation of Article 22 and examine how “the right to contest solely automated decisions” could help give meaning to the overall transparency provisions of the GDPR. With a view to transcend the current debates about the existence of a so-called right to an explanation, the paper develops an interdisciplinary approach, focusing on the specific transparency implications of the “right to contest” as a remedy of procedural nature.

This paper studies the cusp catastrophe in a two-strategy population game with exogenous locational asymmetries and its application to spatial economics. We derive approximating games of two kinds: a cusp catastrophe form and a more general form. As a novel contribution of this paper, the effects of an arbitrary number of regional asymmetries are expressed using only three asymmetry parameters, thereby allowing for an analytical analysis. We find a new behavior with hysteresis using the general form. The usefulness of the forms is demonstrated for two economic geography models. A numerical recipe is presented to construct the cusp catastrophe form.

Purpose To explore the strategies used by older people living in Ireland to obtain information about community health and social services. Methods A qualitative exploratory design was used. Focus groups (n = 3) were conducted with community dwelling older people (n = 17). A series of vignettes were used to guide discussion regarding hypothetical situations that approximated real-life scenarios for older people. Data were transcribed verbatim and analysed using content analysis. Results Obtaining information about community health and social services is an ongoing process that requires continuous commitment by older adults. Key strategies which emerged from the data included (i) taking a proactive stance towards accessing health information, (ii) making use of personal networks in your community and (iii) developing ‘insider’ knowledge. Conclusion Older people in this study had a proactive approach to obtaining health information and identified the importance of taking responsibility for managing their own needs. Despite this, obtaining basic information about community health and social services was a challenging and time-consuming process. Future research should focus on developing health literacy interventions that build upon and expand the strategies currently used by older people.

Studies of industrial symbiosis (IS) focus on the physical flows of materials and energy in local industrial systems. In an ideal IS, waste material and energy are shared or exchanged among the actors of the system, thereby reducing the consumption of virgin material and energy inputs, and likewise the generation of waste and emissions. In this study, the environmental impacts of an industrial ecosystem centered around a pulp and paper mill and operating as an IS are analyzed using life cycle assessment (LCA). The system is compared with two hypothetical reference systems in which the actors would operate in isolation. Moreover, the system is analyzed further in order to identify possibilities for additional links between the actors. The results show that of the total life cycle impacts of the system, upstream processes made the greatest overall contribution to the results. Comparison with stand‐alone production shows that in the case studied, the industrial symbiosis results in modest improvements, 5% to 20% in most impact categories, in the overall environmental impacts of the system. Most of the benefits occur upstream through heat and electricity production for the local town. All in all it is recommended that when the environmental impacts of industrial symbiosis are assessed, the impacts occurring upstream should also be studied, not only the impacts within the ecosystem.

Blood-stage Plasmodium parasites cause morbidity and mortality from malaria. Parasite resistance to drugs makes development of new chemotherapies an urgency. Aminoacyl-tRNA synthetases have been validated as antimalarial drug targets. We explored long-term effects of borrelidin and mupirocin in lethal P. yoelii murine malaria.Long-term (up to 340 days) immunological responses to borrelidin or mupirocin were measured after an initial 4 day suppressive test. Prophylaxis and cure were evaluated and the inhibitory effect on the parasites analysed.Borrelidin protected against lethal malaria at 0.25 mg·kg⁻¹·day⁻¹. Antimalarial activity of borrelidin correlated with accumulation of trophozoites in peripheral blood. All infected mice treated with borrelidin survived and subsequently developed immunity protecting them from re-infection on further challenges, 75 and 340 days after the initial infection. This long-term immunity in borrelidin-treated mice resulted in negligible parasitaemia after re-infections and marked increases in total serum levels of antiparasite IgGs with augmented avidity. Long-term memory IgGs mainly reacted against high and low molecular weight parasite antigens. Immunofluorescence microscopy showed that circulating IgGs bound predominantly to late intracellular stage parasites, mainly schizonts.Low borrelidin doses protected mice from lethal malaria infections and induced protective immune responses after treatment. Development of combination therapies with borrelidin and selective modifications of the borrelidin molecule to specifically inhibit plasmodial threonyl tRNA synthetase should improve therapeutic strategies for malaria.

Issues: This paper identifies and synthesises explanations proposed in the literature for the (in)effectiveness of institutional anti-smoking health-information interventions (HII) among low-socioeconomic status (SES) adults in high-income countries. Approach: We searched eight databases for relevant papers from various disciplines: Studies published in English since 2009, on the effectiveness among low-SES adults of anti-smoking HIIs, aimed at changing knowledge/behaviour, and conducted by official institutions, were included. Through a scoping review, we synthesised: study design, SES indicator, intervention type, intervention source, study population, outcomes, low-SES effects, equity effects, proposed explanations and whether these were studied empirically. Key Findings: Thirty-eight studies were included in this scoping review. Seventeen suggested explanations for the (in)effectiveness of the HIIs in low-SES adults, but only nine assessed them empirically. Thematic analysis yielded six themes: message engagement, material conditions, cognition, risk perception, social environment and self-efficacy. Implications: Explanations for intervention results are not always present, and empirical evidence for explanations is often not provided. Including such explanations and testing their empirical merits in future research can provide the crucial information needed for developing more effective anti-smoking HIIs for low-SES adults. Conclusions: To our knowledge, this is the first review to explore the explanations proposed for why anti-smoking HIIs are (in)effective among low-SES adults. It contains insights for future studies aiming to provide empirical evidence on the causes of this (in)effectiveness, and concludes that such research is yet largely missing, but crucial to the quest for more effective and equitable anti-smoking interventions.