The V-ATPase/ATG16L1 axis is controlled by the V1H subunit.

Defects in organellar acidification indicate compromised or infected compartments. Recruitment of the autophagy-related ATG16L1 complex to pathologically neutralized organelles targets ubiquitin-like ATG8 molecules to perturbed membranes. How this process is coupled to proton gradient disruption is unclear. Here, we reveal that the V1H subunit of the vacuolar ATPase (V-ATPase) proton pump binds directly to ATG16L1. The V1H/ATG16L1 interaction only occurs within fully assembled V-ATPases, allowing ATG16L1 recruitment to be coupled to increased V-ATPase assembly following organelle neutralization. Cells lacking V1H fail to target ATG8s during influenza infection or after activation of the immune receptor stimulator of interferon genes (STING). We identify a loop within V1H that mediates ATG16L1 binding. A neuronal V1H isoform lacks this loop and is associated with attenuated ATG8 targeting in response to ionophores in primary murine and human iPSC-derived neurons. Thus, V1H controls ATG16L1 recruitment following proton gradient dissipation, suggesting that the V-ATPase acts as a cell-intrinsic damage sensor.

Autophagosome membrane expansion is mediated by the N-terminus and cis-membrane association of human ATG8s.

Autophagy is an essential catabolic pathway which sequesters and engulfs cytosolic substrates via autophagosomes, unique double-membraned structures. ATG8 proteins are ubiquitin-like proteins recruited to autophagosome membranes by lipidation at the C-terminus. ATG8s recruit substrates, such as p62, and play an important role in mediating autophagosome membrane expansion. However, the precise function of lipidated ATG8 in expansion remains obscure. Using a real-time in vitro lipidation assay, we revealed that the N-termini of lipidated human ATG8s (LC3B and GABARAP) are highly dynamic and interact with the membrane. Moreover, atomistic MD simulation and FRET assays indicate that N-termini of LC3B and GABARAP associate in cis on the membrane. By using non-tagged GABARAPs, we show that GABARAP N-terminus and its cis-membrane insertion are crucial to regulate the size of autophagosomes in cells irrespectively of p62 degradation. Our study provides fundamental molecular insights into autophagosome membrane expansion, revealing the critical and unique function of lipidated ATG8.

'So Help Me God'? Does oath swearing in courtroom scenarios impact trial outcomes?

In countries such as Britain and the US, court witnesses must declare they will provide truthful evidence and are often compelled to publicly choose between religious ("oath") and secular ("affirmation") versions of this declaration. Might defendants who opt to swear an oath enjoy more favourable outcomes than those who choose to affirm? Two preliminary, pre-registered survey studies using minimal vignettes (Study 1, N = 443; Study 2, N = 913) indicated that people associate choice of the oath with credible testimony; and that participants, especially religious participants, discriminate against defendants who affirm. In a third, Registered Report study (Study 3, N = 1821), we used a more elaborate audiovisual mock trial paradigm to better estimate the real-world influence of declaration choice. Participants were asked to render a verdict for a defendant who either swore or affirmed, and were themselves required to swear or affirm that they would try the defendant in good faith. Overall, the defendant was not considered guiltier when affirming rather than swearing, nor did mock-juror belief in God moderate this effect. However, jurors who themselves swore an oath did discriminate against the affirming defendant. Exploratory analyses suggest this effect may be driven by authoritarianism, perhaps because high-authoritarian jurors consider the oath the traditional (and therefore correct) declaration to choose. We discuss the real-world implications of these findings and conclude the religious oath is an antiquated legal ritual that needs reform.

Does that sound right? A novel method of evaluating models of reading aloud : Rating nonword pronunciations.

Nonword pronunciation is a critical challenge for models of reading aloud but little attention has been given to identifying the best method for assessing model predictions. The most typical approach involves comparing the model's pronunciations of nonwords to pronunciations of the same nonwords by human participants and deeming the model's output correct if it matches with any transcription of the human pronunciations. The present paper introduces a new ratings-based method, in which participants are shown printed nonwords and asked to rate the plausibility of the provided pronunciations, generated here by a speech synthesiser. We demonstrate this method with reference to a previously published database of 915 disyllabic nonwords (Mousikou et al., 2017). We evaluated two well-known psychological models, RC00 and CDP++, as well as an additional grapheme-to-phoneme algorithm known as Sequitur, and compared our model assessment with the corpus-based method adopted by Mousikou et al. We find that the ratings method: a) is much easier to implement than a corpus-based method, b) has a high hit rate and low false-alarm rate in assessing nonword reading accuracy, and c) provided a similar outcome as the corpus-based method in its assessment of RC00 and CDP++. However, the two methods differed in their evaluation of Sequitur, which performed much better under the ratings method. Indeed, our evaluation of Sequitur revealed that the corpus-based method introduced a number of false positives and more often, false negatives. Implications of these findings are discussed.

No evidence for collateral effects of electromagnetic fields used to increase dissolved oxygen levels on the behavior and physiology of freshwater fishes.

Hypoxia in surface waters driven by warming climate and other anthropogenic stressors is a major conservation concern, and technological solutions for water quality remediation are sorely needed. One potential solution involves the use of low-intensity electromagnetic fields (EMFs) to increase dissolved oxygen levels, but potential collateral effects of the EMFs on aquatic animals have not been formally evaluated. We examined the effects of EMF exposure on wild-caught, captive sunfish (Lepomis spp.) over 8-day and 3-day exposures, with and without aeration in mesocosms and stock tanks (respectively). We also quantified ambient fish abundance in close proximity to EMF devices deployed in Opinicon Lake (ON). We found no significant differences in a suite of blood-based stress physiology biomarkers, behaviors, and putative aerobic capacities between EMF and control conditions over 8 days. Aerated mesocosms equipped with activated EMFs consistently had higher oxygen levels in the water than aerated controls. There were no differences in mortality during 3-day oxygen depletion trials under EMF or control conditions, and we detected no differences in fish abundance when the devices were activated in the lake. Our findings suggest that deploying EMF devices in field settings is not likely to exert negative effects on exposed fish populations. PRACTITIONER POINTS: Low-cost, low-energy technological solutions to remediate aquatic hypoxia are sorely needed Electromagnetic fields (EMFs) can increase oxygen flux across air/water interfaces and increase dissolved oxygen levels We found no evidence of negative effects of EMFs on fish physiology or behavior and our results support their use in alleviating hypoxic conditions.

Unveiling the boost in the sandwich priming technique.

The masked priming technique (which compares #####-house-HOUSE vs. #####-fight-HOUSE) is the gold-standard tool to examine the initial moments of word processing. Lupker and Davis showed that adding a pre-prime identical to the target produced greater priming effects in the sandwich technique (which compares #####-HOUSE-house-HOUSE vs #####-HOUSE-fight-HOUSE). While there is consensus that the sandwich technique magnifies the size of priming effects relative to the standard procedure, the mechanisms underlying this boost are not well understood (i.e., does it reflect quantitative or qualitative changes?). To fully characterise the sandwich technique, we compared the sandwich and standard techniques by examining the response times (RTs) and their distributional features (delta plots; conditional-accuracy functions), comparing identity versus unrelated primes. The results showed that the locus of the boost in the sandwich technique was two-fold: faster responses in the identity condition (via a shift in the RT distributions) and slower responses in the unrelated condition. We discuss the theoretical and methodological implications of these findings.

Efficacy information influences intention to take COVID-19 vaccine.

OBJECTIVES: A successful response to the COVID-19 pandemic requires achieving high levels of vaccine uptake. We tested whether directly contrasting the high efficacy of COVID-19 vaccines with the lower efficacy of the annual flu vaccine would increase intentions to take a COVID-19 vaccine. DESIGN: A pre-registered online study of 481 participants compared four information conditions: (1) no information; (2) COVID-19 Vaccine Information Only; and COVID-19 Vaccine Information combined with flu vaccine information suggesting either (3) 60% efficacy or (4) 40% efficacy; we measured COVID-19 and flu vaccine intentions along with several other vaccine-related variables. METHODS: The Prolific platform was used to recruit 481 UK participants (64% female; aged between 18 and 85 years) who had been pre-screened to have intermediate levels of vaccine hesitancy. After reading a short text (~200 words) about COVID-19 vaccines, participants were asked about their vaccination intentions. RESULTS: Providing information about the safety and efficacy of the new COVID-19 vaccines resulted in vaccination intentions that were, on average, 0.39 standard deviations (SDs) higher than those in the no information condition; providing the same COVID vaccine efficacy information in the context of information about flu vaccine efficacy resulted in a further significant increase in vaccination intentions that were 0.68 SD higher than those in the no information condition. This positive contrast effect for the COVID-19 vaccine was not associated with reduced flu vaccine intentions. CONCLUSIONS: Vaccination intentions can be strengthened through a simple messaging intervention that utilizes context effects to increase perceived response efficacy.

Multilayered regulation of autophagy by the Atg1 kinase orchestrates spatial and temporal control of autophagosome formation.

Autophagy is a conserved intracellular degradation pathway exerting various cytoprotective and homeostatic functions by using de novo double-membrane vesicle (autophagosome) formation to target a wide range of cytoplasmic material for vacuolar/lysosomal degradation. The Atg1 kinase is one of its key regulators, coordinating a complex signaling program to orchestrate autophagosome formation. Combining in vitro reconstitution and cell-based approaches, we demonstrate that Atg1 is activated by lipidated Atg8 (Atg8-PE), stimulating substrate phosphorylation along the growing autophagosomal membrane. Atg1-dependent phosphorylation of Atg13 triggers Atg1 complex dissociation, enabling rapid turnover of Atg1 complex subunits at the pre-autophagosomal structure (PAS). Moreover, Atg1 recruitment by Atg8-PE self-regulates Atg8-PE levels in the growing autophagosomal membrane by phosphorylating and thus inhibiting the Atg8-specific E2 and E3. Our work uncovers the molecular basis for positive and negative feedback imposed by Atg1 and how opposing phosphorylation and dephosphorylation events underlie the spatiotemporal regulation of autophagy.

Vision: What's so special about words?

Readers are sensitive to the statistics of written language. New research suggests that this sensitivity may be driven by the same domain-general mechanisms that enable the visual system to detect statistical regularities in the visual environment.

Is zjudge a better prime for JUDGE than zudge is?: A new evaluation of current orthographic coding models.

Three masked priming paradigms, the conventional masked priming lexical-decision task (Forster & Davis, 1984), the sandwich priming task (Lupker & Davis, 2009), and the masked priming same-different task (Norris & Kinoshita, 2008), were used to investigate priming for a given target (e.g., JUDGE) from primes created by either adding a letter to the beginning of the target (e.g., zjudge) or replacing the target's initial letter (e.g., zudge). Virtually all models of orthographic coding that allow calculation of orthographic similarity measures predict that zjudge should be the better prime because zjudge contains all the letters in JUDGE in their correct order whereas zudge does not. Nonetheless, Adelman et al.'s (2014) megastudy data indicated no difference in the effectiveness of these two prime types. The present experiments provide additional support for the conclusion of no difference between these two prime types with the only observed difference being a small zudge prime advantage in Experiment 1b (sandwich priming). These results suggest that models of orthographic coding/word recognition may be well served by allowing inconsistent information (e.g., the "z" in both zjudge and zudge indicates that the presented prime is not JUDGE) to be given considerable weight during the orthographic coding/word recognition process. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The proteasome controls ESCRT-III-mediated cell division in an archaeon.

Sulfolobus acidocaldarius is the closest experimentally tractable archaeal relative of eukaryotes and, despite lacking obvious cyclin-dependent kinase and cyclin homologs, has an ordered eukaryote-like cell cycle with distinct phases of DNA replication and division. Here, in exploring the mechanism of cell division in S. acidocaldarius, we identify a role for the archaeal proteasome in regulating the transition from the end of one cell cycle to the beginning of the next. Further, we identify the archaeal ESCRT-III homolog, CdvB, as a key target of the proteasome and show that its degradation triggers division by allowing constriction of the CdvB1:CdvB2 ESCRT-III division ring. These findings offer a minimal mechanism for ESCRT-III-mediated membrane remodeling and point to a conserved role for the proteasome in eukaryotic and archaeal cell cycle control.

Characterization of progressive changes in pedicle morphometry and neurovascular anatomy during growth in adolescent idiopathic scoliosis versus adolescents without scoliosis.

STUDY DESIGN: Prospective cohort study. OBJECTIVES: Investigate the progressive changes in pedicle morphometry and the spatial relationship between the pedicles and neurovascular structures in patients with AIS during growth. Adolescent idiopathic scoliosis (AIS) is a complex three-dimensional spine deformity. AIS pedicles are known to be asymmetrical when compared to adolescents without scoliosis. Defining the anatomical changes occurring progressively in scoliosis as it increases with time and growth is essential for understanding the pathophysiology of scoliosis and for treatment planning. MRI is the ideal method to study the growing spine without ionising radiation. METHODS: 24 females with AIS (mean 12.6 years, right sided main thoracic curves) and 20 non-scoliotic females (mean 11.5 years) were selected from an ongoing database. Participants underwent two 3D MRI scans (3 T scanner, T1, 0.5 mm isotropic voxels) approximately 1 year apart (AIS: mean 1.3 ± 0.05 years, control: mean 1.0 ± 0.1 years). The pedicle width, chord length, pedicle height, transverse pedicle angle, sagittal pedicle angle, distance from vertebrae to aorta and distance from pedicle to dural sac were measured from T5 to T12. Inter- and intra-observer variability was assessed. RESULTS: From scans 1-2 in the AIS group, the dural sac became closer to the left pedicle (p < 0.05, T6, T8-T10 and T12) while the distance from the vertebrae to the aorta increased (p < 0.05, T6-T10). No significant changes in these measurements were observed in the non-scoliotic group. Between scans, the AIS chord length and transverse pedicle angle increased on the left side around the apex (p < 0.05) creating asymmetries not seen in the non-scoliotic cohort. The mean pedicle height increased symmetrically in the non-scoliosis cohort (p < 0.05) and asymmetrically in the AIS group with the right side growing faster than the left at T6-T7 (p < 0.05). CONCLUSION: Asymmetrical growth patterns occur in the vertebral posterior elements of AIS patients compared to the symmetrical growth patterns found in the non-scoliotic participants. LEVEL OF EVIDENCE: Level II prospective comparative study.

Masked form priming as a function of letter position: An evaluation of current orthographic coding models.

A word's exterior letters, particularly its initial letter, appear to have a special status when reading. Therefore, most orthographic coding models incorporate assumptions giving initial letters and, in some cases, final letters, enhanced importance during the orthographic coding process. In the present article, 3 masked priming experiments were carried out, using the conventional lexical-decision task, the sandwich priming lexical-decision task and the masked priming same-different task, in an attempt to examine a number of those models with a specific focus on the implications of the models' assumptions concerning the different letter positions. The related primes and targets were 6-letter strings that differed in 2 letter positions, initial (e.g., jnckey-HOCKEY), middle (e.g., hojney-HOCKEY), or final (hockjn-HOCKEY), with the middle-letters different primes being the primes that maintained both end letters. To the extent possible, the predictions of the models were derived by using easyNet, the simulation program recently developed by Adelman, Gubian, and Davis (2017). In all experiments, the final-letters different primes were the most effective primes with there being no clear distinction between the other 2 prime types, a pattern that none of the models predicted. The lack of an advantage for the middle-letters different primes suggests that the orthographic code driving masked priming is not one that places a special emphasis on the identities of the exterior letters. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Semantic interpretability does not influence masked priming effects.

Much of the recent masked nonword priming literature demonstrates no difference in priming between affixed and non-affixed nonword primes (e.g., maskity-MASK vs. maskond-MASK). A possible explanation for the absence of a difference is that studies have used affixed primes which were semantically uninterpretable. Therefore, this explanation indicates semantic interpretability plays a fundamental role in masked priming. To test this account, we conducted an experiment using the masked priming paradigm in the lexical decision task. We compared responses with targets which were preceded by one of four primes types: (1) interpretable affixed nonwords (e.g., maskless-MASK), (2) uninterpretable affixed nonwords (e.g., maskity-MASK), (3) non-affixed nonwords (e.g., maskond-MASK), and (4) unrelated words (e.g., tubeful-MASK). Our results follow the trend of finding no difference between affixed and non-affixed primes. Critically, however, we observed no difference in priming between uninterpretable and interpretable affixed primes. Thus, our results suggest that semantic interpretability does not influence masked priming.

Sentiment analysis as a measure of conservation culture in scientific literature.

Culturomics is emerging as an important field within science, as a way to measure attitudes and beliefs and their dynamics across time and space via quantitative analysis of digitized data from literature, news, film, social media, and more. Sentiment analysis is a culturomics tool that, within the last decade, has provided a means to quantify the polarity of attitudes expressed within various media. Conservation science is a crisis discipline; therefore, accurate and effective communication are paramount. We investigated how conservation scientists communicate their findings through scientific journal articles. We analyzed 15,001 abstracts from articles published from 1998 to 2017 in 6 conservation-focused journals selected based on indexing in scientific databases. Articles were categorized by year, focal taxa, and the conservation status of the focal species. We calculated mean sentiment score for each abstract (mean adjusted z score) based on 4 lexicons (Jockers-Rinker, National Research Council, Bing, and AFINN). We found a significant positive annual trend in the sentiment scores of articles. We also observed a significant trend toward increasing negativity along the spectrum of conservation status categories (i.e., from least concern to extinct). There were some clear differences in the sentiments with which research on different taxa was reported, however. For example, abstracts mentioning lobe finned fishes tended to have high sentiment scores, which could be related to the rediscovery of the coelacanth driving a positive narrative. Contrastingly, abstracts mentioning elasmobranchs had low scores, possibly reflecting the negative sentiment score associated with the word shark. Sentiment analysis has applications in science, especially as it pertains to conservation psychology, and we suggest a new science-based lexicon be developed specifically for the field of conservation.

El Análisis de Opinión como Medida de la Cultura de Conservación en la Literatura Científica Lennox et al. Resumen La culturomía está emergiendo como un campo importante dentro de la ciencia pues es una manera de medir las actitudes, creencias y sus dinámicas a través del tiempo y el espacio por medio de un análisis cuantitativo de datos digitalizados a partir de la literatura, las noticias, las películas, las redes sociales y otros medios. El análisis de opinión es una herramienta de la culturomía que, en la última década, ha proporcionado los medios para cuantificar la polaridad de las actitudes expresadas en varios medios. La ciencia de la conservación es una disciplina de crisis; por lo tanto, la comunicación certera y efectiva es de suma importancia. Investigamos cómo los científicos de la conservación comunican sus hallazgos por medio de los artículos en las revistas científicas. Analizamos 15,001 resúmenes de artículos publicados entre 1998 y 2017 en seis revistas enfocadas en la conservación que fueron seleccionados con base en los índices de las bases de datos científicos. Categorizamos los artículos por año, taxón de enfoque y el estado de conservación de la especie focal. Calculamos la opinión promedio para cada resumen (puntaje z ajustado a la media) con base en cuatro lexicones (Jockers-Rinker, National Research Council, Bing y AFINN). Encontramos una significativa tendencia positiva anual en los puntajes de opinión de los artículos. También observamos una tendencia significativa hacia el incremento en la negatividad a lo largo del espectro de categorías de estado de conservación (es decir, de aquellas de menos preocupación a aquellas en peligro crítico o extintas). Sin embargo, hubo algunas diferencias claras en las opiniones con las cuales se reportaron las investigaciones sobre los diferentes taxones. Por ejemplo, los resúmenes que mencionaron a los peces de aletas lobuladas tendieron hacia los puntajes altos de opinión, lo que podría relacionarse con el redescubrimiento del celacanto como causa de una narrativa positiva. En contraste, los resúmenes que mencionaron a los elasmobranquios tuvieron puntajes bajos, lo que refleja el puntaje de opinión negativa asociado con la palabra tiburón. El análisis de opinión tiene aplicaciones en la ciencia, especialmente como parte de la psicología de la conservación, y sugerimos que se desarrolle un nuevo lexicón basado en la ciencia específicamente para el campo de la conservación.

Evidence from masked-priming that initial identification of brand names is via abstract letter identities.

Although visual-word recognition is often assumed to proceed on the basis of case-invariant letter representations, previous research has shown a role for letter-case in recognizing brand names. One recent study reported early effects of letter-case in a brand-decision task using masked primes (Perea et al., 2015, British Journal of Psychology, 106, 162). The present study attempts to replicate this finding using brand names typically presented in all lowercase (e.g., adidas), all uppercase (e.g., IKEA), or titlecase (e.g., Ford). Across three masked-priming experiments, we found no advantage for case-matched identity primes over case-mismatched identity primes. This finding suggests that brand-specific letter-case information does not play a role in the early processing of brand names. However, we observed evidence that case may be used as a cue for making brand decisions, which may explain the effect reported by Perea et al. (2015, British Journal of Psychology, 106, 162).

Forcing the reversibility of a mechanochemical reaction.

Mechanical force modifies the free-energy surface of chemical reactions, often enabling thermodynamically unfavoured reaction pathways. Most of our molecular understanding of force-induced reactivity is restricted to the irreversible homolytic scission of covalent bonds and ring-opening in polymer mechanophores. Whether mechanical force can by-pass thermodynamically locked reactivity in heterolytic bimolecular reactions and how this impacts the reaction reversibility remains poorly understood. Using single-molecule force-clamp spectroscopy, here we show that mechanical force promotes the thermodynamically disfavored SN2 cleavage of an individual protein disulfide bond by poor nucleophilic organic thiols. Upon force removal, the transition from the resulting high-energy unstable mixed disulfide product back to the initial, low-energy disulfide bond reactant becomes suddenly spontaneous, rendering the reaction fully reversible. By rationally varying the nucleophilicity of a series of small thiols, we demonstrate how force-regulated chemical kinetics can be finely coupled with thermodynamics to predict and modulate the reversibility of bimolecular mechanochemical reactions.

A backwards glance at words: Using reversed-interior masked primes to test models of visual word identification.

The experiments reported here used "Reversed-Interior" (RI) primes (e.g., cetupmor-COMPUTER) in three different masked priming paradigms in order to test between different models of orthographic coding/visual word recognition. The results of Experiment 1, using a standard masked priming methodology, showed no evidence of priming from RI primes, in contrast to the predictions of the Bayesian Reader and LTRS models. By contrast, Experiment 2, using a sandwich priming methodology, showed significant priming from RI primes, in contrast to the predictions of open bigram models, which predict that there should be no orthographic similarity between these primes and their targets. Similar results were obtained in Experiment 3, using a masked prime same-different task. The results of all three experiments are most consistent with the predictions derived from simulations of the Spatial-coding model.

Diagnostic accuracy of Cancer Antigen 125 (CA125) for endometriosis in symptomatic women: A multi-center study.

STUDY OBJECTIVE: To assess the diagnostic accuracy of serum Cancer Antigen 125 (CA 125)≥30units/milliliter (u/ml) for diagnosing endometriosis in symptomatic women. STUDY DESIGN: Prospective observational cohort study including patients with symptoms of pelvic pain or subfertility undergoing elective diagnostic laparoscopy at two tertiary referral hospitals. We excluded patients suspected to have other gynecological pathology. We evaluated the accuracy of serum CA 125 (index test) with histologically confirmed endometriosis (reference standard). MAIN RESULTS: Fifty-eight consecutive women recruited between October 2013 to March 2015. Women with endometriosis had a higher CA 125 level than those without endometriosis (mean 54.7+/-71.6 vs 16.2+/- 8.0). The specificity of CA 125≥30u/ml was 96% (95% CI 81.7-99.9%) and sensitivity was 57% (95% CI 37.4-74.5%). The positive likelihood ratio for the histological presence of endometriosis with a CA 125≥30u/ml was 15.8 (95% CI 2.3-112) providing a post-test probability of 94% (95% CI 71%-99%) in women with pelvic pain or subfertility. The area under the curve, 0.85 (95% CI 0.74-0.96) indicates high test accuracy. CONCLUSIONS: CA 125≥30u/ml is highly predictive of endometriosis in women with symptoms of pain and/or subfertility. CA 125 should be considered as a rule-in test for expediting the diagnosis and management of endometriosis, CA 125 <30u/ml is, however, unable to rule out endometriosis.