bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effects of Education on Mortality: Evidence From Linked U.S. Census and Administrative Mortality Data
Authors: Halpern-Manners Andrew , Helgertz Jonas , Warren John Robert , Roberts Evan
Published: July 2020

Does education change people’s lives in a way that delays mortality? Or is education primarily a proxy for unobserved endowments that promote longevity? Most scholars conclude that the former is true, but recent evidence based on Danish twin data calls this conclusion into question. Unfortunately, these potentially field-changing findings—that obtaining additional schooling has no independent effect on survival net of other hard-to-observe characteristics—have not yet been subject to replication outside Scandinavia. In this article, we produce the first U.S.-based estimates of the effects of education on mortality using a representative panel of male twin pairs drawn from linked complete-count census and death records. For comparison purposes, and to shed additional light on the roles that neighborhood, family, and genetic factors play in confounding associations between education and mortality, we also produce parallel estimates of the education-mortality relationship using data on (1) unrelated males who lived in different neighborhoods during childhood, (2) unrelated males who shared the same neighborhood growing up, and (3) non-twin siblings who shared the same family environment but whose genetic endowments vary to a greater degree. We find robust associations between education and mortality across all four samples, although estimates are modestly attenuated among twins and non-twin siblings. These findings—coupled with several robustness checks and sensitivity analyses—support a causal interpretation of the association between education and mortality for cohorts of boys born in the United States in the first part of the twentieth century.
Synthesis of Fe3O4/ZnO nanoparticles and their application for the photodegradation of anionic and cationic dyes
Authors: Długosz O. , Szostak K. , Krupiński M. , Banach M.
Published: July 2020

Multifunctional materials have become an important research subject in recent years. Zinc oxide nanoparticles (ZnO NP) deposited on iron oxide (Fe3O4) allow to obtain material with photocatalytic and magnetic properties. The mass share of Fe3O4in the composite was 30%. Saturation magnetization for this sample was about 9.5 emu/g. The use of magnetic material allows to recover the photocatalyst after the photodegradation process and reuse it. The possibility of recovery of Fe3O4nanoparticles with a magnet was estimated at 94.80%, while the recovery of Fe3O4/ZnO achieved 83.91%. The effects of the type of dyes (Methylene Blue, Methyl Orange, Quinoline Yellow, Eriochromic Black T and Trypanic Blue) on their photodegradation efficiency in terms of molar mass of the dye, the solvent in which the processes were carried out and the type of dye charge were investigated. The photocatalytic material showed higher photodegradation activity of dyes while increasing their molar mass. ZnO NPs deposited on Fe3O4 presented 95.61% photocatalytic efficiency against Trypan Blue and 63.02% against Methylene Blue. Increasing the surface area of the catalyst to 39 m2/g and the presence of micro-, meso- and macropores had a positive effect on the sorption process of dyes, especially those of larger sizes, allowing their degradation in the photodegradation process.
Participatory governance in Lake Victoria (Kenya) fisheries: whose voices are heard?
Authors: Etiegni Christine Adhiambo , Irvine Kenneth , Kooy Michelle
Published: July 2020

Co-management is advocated as a means to improve human equity and the ecological sustainability of common-pool resources. The promotion of co-management of fisheries often assumes the participation of resource users in decision-making ensures more ecologically sustainable outcomes than top–down management approaches while improving livelihoods and food security. However, in fisheries co-management approaches, participation is often poorly defined and measured by co-management proponents. For resource users, it may not be clear what their participation in co-management entails, and what such participation might involve or achieve. For the fisheries of Lake Victoria (Kenya), the introduction of co-management established Beach Management Units (BMUs) on a model of participatory decision-making. Unsurprisingly, given global experiences of institutions for resource users’ participation in co-management, the structures established across Lake Victoria (Kenya) have not resulted in effective participation of fisher folk. We examine why this is so. Specifically, we examine the influence of institutions on fisher folks’ participation in co-management, using critical institutionalism to explain how participation of resource users is shaped by the relation between formal government institutions and informal social norms. We take four BMUs as case studies to investigate how historical administrative structures shape the development of co-management, how power relationships within co-management are negotiated at the local beach level and the fisher folks’ understanding of their participation in co-management. We document how informal institutions undermine and replace formal institutions at the local beach level, while formal institutions suppress and ignore informal ones at the national and regional levels. From this, we argue power sharing between the government and fisher folk is key for fisher folk participation in fisheries co-management, capable of addressing both social and ecological challenges facing fisheries management.
Neanderthals as familiar strangers and the human spark: How the ‘golden years’ of Neanderthal research reopen the question of human uniqueness
Authors: Peeters Susan , Zwart Hub
Published: July 2020

During the past decades, our image ofHomo neanderthalensishas changed dramatically. Initially, Neanderthals were seen as primitive brutes. Increasingly, however, Neanderthals are regarded as basically human. New discoveries and technologies have led to an avalanche of data, and as a result of that it becomes increasingly difficult to pinpoint what the difference between modern humans and Neanderthals really is. And yet, the persistent quest for a minimal difference which separates them from us is still noticeable in Neanderthal research. Neanderthal discourse is a vantage point from which the logic of ‘us’ versus ‘other’ is critically reconsidered. Studying contemporary academic literature and science autobiographies from an oblique perspective, focusing not on Neanderthals as objects, but on the dynamics of interaction between Neanderthal researchers and their finds, basic convictions at work in this type of research are retrieved. What is at issue is not the actual distinction between modern humans and Neanderthals (which is continuously being redefined), but rather the dualistic construction of human and nonhuman. Neanderthal understanding is affected by the desire to safeguard human uniqueness. The overall trend is to identify the human mark or spark, which defines us as favoured ‘winners’. The paradoxes emerging in contemporary Neanderthal discourse are symptomatic of the fact that a dualistic style of thinking is no longer tenable.
Visits at artificial RFID flowers demonstrate that juvenile flower-visiting bats perform foraging flights apart from their mothers
Authors: Rose Andreas , Tschapka Marco , Knörnschild Mirjam
Published: July 2020

During the transition from parental care to independent life, the development of adequate foraging skills is a major challenge for many juvenile mammals. However, participating in their parents’ knowledge by applying social learning strategies might facilitate this task. For several mammals, communal foraging of adults and offspring is suggested to be an important mechanism in mediating foraging-related information. For the large mammalian taxon of bats, only little is known about foraging-related social learning processes during ontogeny. It is often suggested that following their mothers during foraging flights would represent a valuable option for juveniles to socially learn about foraging, e.g., where to find resource-rich foraging patches, but explicit tests are scarce. In the present study, we investigated the foraging behavior of juvenile flower-visiting bats (Glossophaga soricina) in a dry forest in Costa Rica. We tested whether recently volant, but still nursed pups perform foraging flights alone, or whether pups follow their mothers, which would enable pups to socially learn where to feed. For that, we trained mothers and pups to feed from artificial flowers with a RFID reading system and, subsequently, conducted a field experiment to test whether RFID-tagged mothers and pups visit these flowers communally or independently. Unexpectedly, pups often encountered and visited artificial flowers near the day roost, while mothers rarely did, suggesting that they foraged somewhere further away. Our results demonstrate that still nursed juveniles perform foraging flights apart from their mothers and might learn about the spatial distribution of food without participating in their mother’s knowledge, for instance, by following other conspecifics or applying individual learning strategies. An initial potential lack of foraging success in this period is likely compensated by the ongoing maternal provisioning with breast milk and regurgitated nectar during daytime. Our results contribute to the growing body of research on the ontogeny of mammalian foraging behavior in general.
Comparison of Hiraoka's Transurethral Detachment Prostatectomy and Transurethral Resection of the Prostate Effects on Postoperative Erectile Function in Patients with Benign Prostatic Hyperplasia: A Prospective Randomized Controlled Study
Authors: Pan Chunyu , Zhan Yunhong , Zhao Yueyang , Wu Bin , Bai Song
Published: July 2020

Background

Currently, no study has focused on the postoperative erectile function in patients with benign prostatic hyperplasia (BPH) by comparing Hiraoka's transurethral detachment of prostate (TUDP) and transurethral resection of prostate (TURP).

Aim

To compare the effects of Hiraoka's TUDP and TURP on postoperative erectile function in patients with BPH after long-term follow-up.

Methods

A total of 104 consecutive patients with BPH treated in our hospital between September 2018 and February 2019 were included in the study. All patients who met the inclusion criteria were randomly divided into the Hiraoka's TUDP (n = 52) and TURP (n = 52) groups. Patient baseline data were collected. The international index of erectile function (IIEF-5), minimal clinically important difference (MCID), and quality of life scale (QOLS) were used to evaluate erectile function and quality of life 3, 6, and 12 months after surgery. Primary study endpoints were IIEF-5 and MCID. Secondary study endpoints were QOLS and independent prognostic factors for MCID.

Outcomes

Hiraoka's TUDP experienced greater improvement in postoperative IIEF5 scores than patients who underwent TURP.

Results

Patients in the Hiraoka's TUDP group had significantly higher mean IIEF-5 scores than those in the TURP group 6 and 12 months after surgery (6 months: 18.9 vs 14.8, P < .001; 12 months: 18.1 vs 15.7, P < .001). The percentages of patients in the TUDP group who achieved an MCID were 88.5% and 80.8%, compared to 30.8% and 46.2% in the TURP group (P < .001 for both), 6 and 12 months after the operation, respectively. Patients in the TUDP group had lower QOLS scores than those in the TURP group after the surgery. The surgical method was an independent prognostic factor for MCID (odds ratio = 0.218).

Clinical Implications

Until now, no study has focused on the postoperative erectile function in patients with BPH by comparing Hiraoka's TUDP and TURP. Our study addressed this issue, which can add a new paradigm in the management to BPH.

Strength & Limitations

The comparison between Hiraoka's TUDP and TURP using a statistically appropriate, adequately powered methodology is the strength of the study. The single center and less participants are the limitations of the study. We believe that multicenter and large-sample studies are needed to further verify these study conclusions.

Conclusions

Among similar cohorts of patients with BPH who underwent TUDP and TURP, patients who underwent Hiraoka's TUDP experienced greater improvement in postoperative IIEF5 scores than patients who underwent TURP, while improvement in IPSS was similar among both groups.
Writing in the Margins of Sexual Function Questionnaires: A Qualitative Analysis of Data from Women with Pelvic Floor Disorders
Authors: Parameshwar Pooja S. , Borok Jenna F. , Jung Eric E. , Thum Lauren Wood , Ackerman Anne Lenore , Eilber Karyn S. , Anger Jennifer T.
Published: July 2020

Background

The impact of pelvic floor disorders (PFDs) on female sexual function is not well understood, partly due to difficulties in measurement and evaluation.

Aim

We sought to assess how women with PFDs respond to sexual function questionnaires through an analysis of survey marginalia, or the comments written in the margins of fixed-choice surveys.

Methods

94 women with PFDs completed validated written sexual function questionnaires (Global Study of Sexual Attitudes and Behaviors survey, Female Sexual Function Index, and the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire, International Urogynecological Association-Revised). Marginalia, or the additions, eliminations, and changes subjects made (by hand) to survey items, were collected. Data were coded and analyzed qualitatively using grounded theory methodology.

Outcomes

Themes and emergent concepts related to the content of survey marginalia were the primary outcomes of this study.

Results

We observed 177 instances of marginalia across all questionnaires. Qualitative analysis revealed 7 preliminary themes and 2 emergent concepts. Preliminary themes included partner-related topics, loss, problems during intercourse, emotional problems, other medical problems, and survey answer choices failing to capture the spectrum of patient experiences. Emergent concepts revealed highly diverse sexual function in this population and a wide range of factors that influence sexual function.

Clinical Implications

Conducting qualitative studies alongside sexual function questionnaires can allow for a more meaningful assessment of the sexual function of women with various underlying conditions, such as PFDs.

Strengths & Limitations

This is the first study of its kind to analyze survey marginalia from sexual function questionnaires among women with PFDs. The limitations of this study include the inherently spontaneous nature of marginalia data. In addition, the ways in which study participants responded to sexual function questionnaires in our study may not be reflective of all potential subjects.

Conclusion

Analysis of survey marginalia from sexual function questionnaires amongst women with PFDs revealed new information regarding patients' histories, concerns, and thoughts. Over half of the women in this study felt the need to expand, explain, or eliminate responses from the questionnaires. Many subjects were no longer sexually active, which accounted for a large majority of participants leaving questions blank or responding with “N/A.” Standard sexual evaluation tools may fail to capture the complexity, spectrum, and depth and breadth of patient experiences.
τ-Tilting finite cluster-tilted algebras
Authors: Zito Stephen
Published: July 2020

We prove if B is a cluster-tilted algebra, then B is τB-tilting finite if and only if B is representation-finite.
Exploring seed longevity of UK native trees: implications for ex situ conservation
Authors: Davies Rachael M. , Hudson Alice R. , Dickie John B. , Cook Charlotte , O'Hara Tom , Trivedi Clare
Published: July 2020

UK trees require increased conservation efforts due to sparse and fragmented populations. Ex situ conservation, including seed banking, can be used to better manage these issues. We conducted accelerated ageing tests on seeds of 22 UK native woody species, in order to assess their likely longevity and optimize their conservation in a seed bank. Germination at four ageing time points was determined to construct survival curves, and it was concluded that multiple samples within a species showed comparable responses for most species tested, except for Fraxinus excelsior. Of all species studied, one could be classified as very short-lived, four as short-lived and 17 as medium, with none exceeding the medium category. The most important finding of this manuscript is that although some taxonomic trends were observed, the results indicate the need for caution when making broad conclusions on potential seed storage life at a species, genus or family level. Longevity predictions were compared to actual performance of older collections held in long-term storage at the Millennium Seed Bank, Kew. Although most collections remain high in viability in storage after more than 20 years, for short-lived species at least, there is some indication that accelerated ageing predicts longevity in seed bank conditions. For species with reduced potential longevity, such as Fagus sylvatica and Ulmus glabra, additional storage options are recommended for long-term gene banking.
Anxiety, fear, and ontological security in world politics: thinking with and beyond Giddens
Authors: Kinnvall Catarina , Mitzen Jennifer
Published: July 2020

Research on ontological security in world politics has mushroomed since the early 2000s but seems to have reached an impasse. Ontological security is a conceptual lens for understanding subjectivity that focuses on the management of anxiety in self-constitution. Building especially on Giddens, IR scholars have emphasized how this translates to a need for cognitive consistency and biographical continuity – a security of ‘being.’ A criticism has been its so-called ‘status quo bias,’ a perceived tilt toward theorizing investment in the existing social order. To some, an ontological security lens both offers social theoretic foundations for a realist worldview and lacks resources to conceptualize alternatives. We disagree. Through this symposium, we address that critique and suggest pathways forward by focusing on the thematic of anxiety. Distinguishing between anxiety and fear, we note that anxiety manifests in different emotions and leaves room for a range of political possibilities. Early ontological security scholarship relied heavily on readings of Giddens, which potentially accounts for its bias. This symposium re-opens the question of the relationship between anxiety and subjectivity from the perspective of ontological security, thinking with and beyond Giddens. Three contributions re-think anxiety in ontological security drawing on existentialist philosophy; two address limitations of Giddens' approach.
The Effects of Field Line Curvature (FLC) Scattering on Ring Current Dynamics and Isotropic Boundary
Authors: Yu Yiqun , Tian Xingbin , Jordanova Vania K.
Published: July 2020

In the ring current dynamics, various loss mechanisms contribute to the ring current decay, including losses to the upper atmosphere through particle precipitation. This study implements the field line curvature (FLC) scattering mechanism in a kinetic ring current model and investigates its role in precipitating ions into the ionosphere during the 17 March 2013 storm. Simulation results indicate that (1) the FLC scattering process exerts on energetic ions on the nightside where the magnetospheric configuration is more stretching. It is more effective on heavy ions (e.g., O+). These ion losses thereafter lead to a faster recovery of the ring current. (2) The FLC‐associated ion precipitation mainly occurs in the outer region (L > 5 for protons and L > 4.5 for oxygen ions) on the nightside. The O+ precipitation takes places in a wider region than protons although its intensity is much lower. Comparisons with POES observations suggest that more proton precipitation is needed in the inner region. This is probably caused by the less stretched configuration in the simulation that prevents more precipitation. It may also imply that other loss process is required in the model such as wave‐particle interactions. (3) The storm time precipitating proton flux of tens of keV due to the FLC scattering sometimes becomes comparable to that of electrons on the nightside, although electrons usually dominate the ionospheric energy deposition from the midnight eastward toward the dayside. (4) The FLC scattering process seems to be capable of explaining the formation of isotropic boundary in the ionosphere during the investigated event.
Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: a cross-diagnostic cluster analysis on a large, international, observational study
Authors: Corponi Filippo , Anmella Gerard , Pacchiarotti Isabella , Samalin Ludovic , Verdolini Norma , Popovic Dina , Azorin Jean-Michel , Angst Jules , Bowden Charles L. , Mosolov Sergey , Young Allan H. , Perugi Giulio , Vieta Eduard , Murru Andrea
Published: July 2020

A cross-diagnostic, post-hoc analysis of the BRIDGE-II-MIX study was performed to investigate how unipolar and bipolar patients suffering from an acute major depressive episode (MDE) cluster according to severity and duration. Duration of index episode, Clinical Global Impression-Bipolar Version-Depression (CGI-BP-D) and Global Assessment of Functioning (GAF) were used as clustering variables. MANOVA and post-hoc ANOVAs examined between-group differences in clustering variables. A stepwise backward regression model explored the relationship with the 56 clinical-demographic variables available. Agglomerative hierarchical clustering with two clusters was shown as the best fit and separated the study population (n = 2314) into 65.73% (Cluster 1 (C1)) and 34.26% (Cluster 2 (C2)). MANOVA showed a significant main effect for cluster group (p < 0.001) but ANOVA revealed that significant between-group differences were restricted to CGI-BP-D (p < 0.001) and GAF (p < 0.001), showing greater severity in C2. Psychotic features and a minimum of three DSM-5 criteria for mixed features (DSM-5-3C) had the strongest association with C2, that with greater disease burden, while non-mixed depression in bipolar disorder (BD) type II had negative association. Mixed affect defined as DSM-5-3C associates with greater acute severity and overall impairment, independently of the diagnosis of bipolar or unipolar depression. In this study a pure, non-mixed depression in BD type II significantly associates with lesser burden of clinical and functional severity. The lack of association for less restrictive, researched-based definitions of mixed features underlines DSM-5-3C specificity. If confirmed in further prospective studies, these findings would warrant major revisions of treatment algorithms for both unipolar and bipolar depression.
Deletion of NRXN1α impairs long-range and local connectivity in amygdala fear circuit
Authors: Asede Douglas , Joseph Asnel , Bolton McLean M.
Published: July 2020

Neurexins are a family of presynaptic cell adhesion proteins that regulate synaptic structure and maintain normal synaptic transmission. Mutations in the α-isoform of neurexin1-gene (NRXN1α) are linked with cognitive and emotional dysregulation, which are heavily dependent on the amygdala and medial prefrontal cortex (mPFC). It is however not known whether deletion ofNRXN1αgene affect specific synaptic elements within the amygdala microcircuit and connectivity with mPFC. In this study, we show thatNRXN1αdeletion impairs synaptic transmission between the dorsal medial prefrontal cortex (dmPFC) and basal amygdala (BA) principal neurons. Stimulation of dmPFC fibers resulted in reduced paired pulse ratio (PPR) and AMPA/NMDA ratio at dmPFC to BA synapses inNRXN1α-knockout (KO) (NRXN1αKO) mice suggestive of pre- and postsynaptic deficits but there was no change at the lateral amygdala (LA) to BA synapses following LA stimulation. However, feedforward inhibition from either pathway was significantly reduced, suggestive of input-independent deficit in GABAergic transmission within BA. We further analyzed BA inhibitory network and found reduced connectivity between BA GABAergic and glutamatergic neurons inNRXN1αKO mice. As this circuit is tightly linked with fear regulation, we subjectedNRXN1αKO and WT mice to discriminative fear conditioning and found a deficit in fear memory retrieval inNRXN1αKO mice compared with WT mice. Together, we provide novel evidence that deletion ofNRNX1αdisrupts amygdala fear circuit.
Computational analysis of TP53 mutational landscape unveils key prognostic signatures and distinct pathobiological pathways in head and neck squamous cell cancer
Authors: Caponio Vito Carlo Alberto , Troiano Giuseppe , Adipietro Iolanda , Zhurakivska Khrystyna , Arena Claudia , Mangieri Domenica , Mascitti Marco , Cirillo Nicola , Lo Muzio Lorenzo
Published: July 2020

Background

Mutations of the tumour-suppressor gene TP53 are the most frequent somatic genomic alterations in head and neck squamous cell carcinoma (HNSCC). However, it is not yet clear whether specific TP53 mutations bear distinct clinical and pathophysiological significance in different HNSCC subgroups.

Methods

A systematic bioinformatics appraisal of TP53 mutations was performed on 415 HNSCC cases available on The Cancer Genome Atlas (TCGA). The following features were analysed and correlated with known clinicopathological variables: mutational profile of TP53, location (within secondary structure and predicted domains of p53 protein) and well-known hotspot mutations. Interactome–genome–transcriptome network analysis highlighted different gene networks. An algorithm was generated to develop a new prognostic classification system based on patients’ overall survival.

Results

TP53 mutations in HNSCCs exhibited distinct differences in different anatomical sites. The mutational profile of TP53 was an independent prognostic factor in HNSCC. High risk of death mutations, identified by our novel classification algorithm, was an independent prognostic factor in TCGA HNSCC database. Finally, network analysis suggested that distinct p53 molecular pathways exist in a site- and mutation-specific manner.

Conclusions

The mutational profile of TP53 may serve as an independent prognostic factor in HNSCC patients, and is associated with distinctive site-specific biological networks.
Autophagy is involved in the protective effect of p21 on LPS-induced cardiac dysfunction
Authors: Huang Sihui , Xu Man , Liu Libo , Yang Jingjing , Wang Huibo , Wan Chunxia , Deng Wei , Tang Qizhu
Published: July 2020

p21 has emerged as an important protein involved in cardiovascular diseases, but its role remains controversial. Recently, p21 has been reported to mediate inflammatory responses. As inflammatory responses are a feature of sepsis, our study investigated whether p21 has a role in cardiac dysfunction induced by sepsis and analyzed the mechanisms involved. To establish a mouse sepsis model, p21 global knockout (p21KO) and C57BL/6J wild-type (WT) male mice were treated with 5 mg/kg LPS intraperitoneally for 6, 24, or 48 h. After LPS stimulation, the level of p21 had significantly increased in the WT mice and in cardiomyocytes. Cardiac dysfunction induced by LPS was markedly aggravated in p21KO mice relative to that of WT mice. Downregulation of p21 expression exacerbated the LPS-mediated inflammatory response, and it increased oxidative stress as well as mitochondrial damage in the heart and in cardiomyocytes. In contrast, overexpressing p21 attenuated the increase of TNFα and promoted the increase of SOD2. Moreover, p21 regulated the LPS-induced autophagy activation; that is, the increase in autophagy was impaired when p21 expression was decreased, whereas the increase was significant when p21 was overexpressed. The autophagy inducer rapamycin partially rescued the cardiac deterioration caused by p21 downregulation in the LPS-stimulated groups. In addition, p21 regulated the autophagy level by interacting with LC3B. These results revealed that p21 controls LPS-induced cardiac dysfunction by modulating inflammatory and oxidative stress, and it is partially dependent on regulating the autophagy level. This study is the first to show that p21 could interact with LC3B to promote autophagy for the improvement of cardiac function during sepsis.
Asteroid shower on the Earth-Moon system immediately before the Cryogenian period revealed by KAGUYA
Authors: Terada Kentaro , Morota Tomokatsu , Kato Mami
Published: July 2020

Meteoroid bombardment of the Earth-Moon system must have caused catastrophic damage to the terrestrial ecosphere. However, ancient meteoroid impacts and their relations to environmental changes are not well understood because of erosion and/or resurfacing processes on Earth. Here, we investigate the formation ages of 59 lunar craters with fresh morphologies and diameters greater than approximately 20 km and first find that 8 of 59 craters were formed simultaneously. Considering the radiometric ages of ejecta from Copernicus crater and impact glass spherules from various Apollo landing sites, we conclude that sporadic meteoroid bombardment occurred across the whole Moon at approximately 800 Ma. Based on crater scaling laws and collision probabilities with the Earth and Moon, we suggest that at least (4–5) × 1016 kg of meteoroids, approximately 30–60 times more than the Chicxulub impact, must have plunged into the Earth-Moon system immediately before the Cryogenian, which was an era of great environmental changes.
Orexin signaling modulates synchronized excitation in the sublaterodorsal tegmental nucleus to stabilize REM sleep
Authors: Feng Hui , Wen Si-Yi , Qiao Qi-Cheng , Pang Yu-Jie , Wang Sheng-Yun , Li Hao-Yi , Cai Jiao , Zhang Kai-Xuan , Chen Jing , Hu Zhi-An , Luo Fen-Lan , Wang Guan-Zhong , Yang Nian , Zhang Jun
Published: July 2020

The relationship between orexin/hypocretin and rapid eye movement (REM) sleep remains elusive. Here, we find that a proportion of orexin neurons project to the sublaterodorsal tegmental nucleus (SLD) and exhibit REM sleep-related activation. In SLD, orexin directly excites orexin receptor-positive neurons (occupying ~3/4 of total-population) and increases gap junction conductance among neurons. Their interaction spreads the orexin-elicited partial-excitation to activate SLD network globally. Besides, the activated SLD network exhibits increased probability of synchronized firings. This synchronized excitation promotes the correspondence between SLD and its downstream target to enhance SLD output. Using optogenetics and fiber-photometry, we consequently find that orexin-enhanced SLD output prolongs REM sleep episodes through consolidating brain state activation/muscle tone inhibition. After chemogenetic silencing of SLD orexin signaling, a ~17% reduction of REM sleep amounts and disruptions of REM sleep muscle atonia are observed. These findings reveal a stabilization role of orexin in REM sleep.
Molecular basis of host-adaptation interactions between influenza virus polymerase PB2 subunit and ANP32A
Authors: Camacho-Zarco Aldo R. , Kalayil Sissy , Maurin Damien , Salvi Nicola , Delaforge Elise , Milles Sigrid , Jensen Malene Ringkjøbing , Hart Darren J. , Cusack Stephen , Blackledge Martin
Published: July 2020

Avian influenza polymerase undergoes host adaptation in order to efficiently replicate in human cells. Adaptive mutants are localised on the C-terminal (627-NLS) domains of the PB2 subunit. In particular, mutation of PB2 residue 627 from E to K rescues polymerase activity in mammalian cells. A host transcription regulator ANP32A, comprising a long C-terminal intrinsically disordered domain (IDD), is responsible for this adaptation. Human ANP32A IDD lacks a 33 residue insertion compared to avian ANP32A, and this deletion restricts avian influenza polymerase activity. We used NMR to determine conformational ensembles of E627 and K627 forms of 627-NLS of PB2 in complex with avian and human ANP32A. Human ANP32A IDD transiently binds to the 627 domain, exploiting multivalency to maximise affinity. E627 interrupts the polyvalency of the interaction, an effect compensated by an avian-unique motif in the IDD. The observed binding mode is maintained in the context of heterotrimeric influenza polymerase, placing ANP32A in the immediate vicinity of known host-adaptive PB2 mutants.
Author Correction: High permeability sub-nanometre sieve composite MoS2 membranes
Authors: Sapkota Bedanga , Liang Wentao , VahidMohammadi Armin , Karnik Rohit , Noy Aleksandr , Wanunu Meni
Published: July 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A new island-scale tropical cyclone outlook for southwest Pacific nations and territories
Authors: Magee Andrew D. , Lorrey Andrew M. , Kiem Anthony S. , Colyvas Kim
Published: July 2020

The southwest Pacific (SWP) region is vulnerable to tropical cyclone (TC) related impacts which adversely affect people, infrastructure and economies across several nations and territories. Skilful TC outlooks are needed for this region, but the erratic nature of SWP TCs and the complex ocean–atmosphere interactions that influence TC behaviour on seasonal timescales presents significant challenges. Here, we present a new TC outlook tool for the SWP using multivariate Poisson regression with indices of multiple climate modes. This approach provides skilful, island-scale TC count outlooks from July (four months ahead of the official TC season start in November). Monthly island-scale TC frequency outlooks are generated between July and December, enabling continuous refinement of predicted TC counts before and during a TC season. Use of this approach in conjunction with other seasonal climate guidance (including dynamical models) has implications for preparations ahead of severe weather events, resilience and risk reduction.
Distinct and stage-specific contributions of TET1 and TET2 to stepwise cytosine oxidation in the transition from naive to primed pluripotency
Authors: Mulholland Christopher B. , Traube Franziska R. , Ugur Enes , Parsa Edris , Eckl Eva-Maria , Schönung Maximilian , Modic Miha , Bartoschek Michael D. , Stolz Paul , Ryan Joel , Carell Thomas , Leonhardt Heinrich , Bultmann Sebastian
Published: July 2020

Cytosine DNA bases can be methylated by DNA methyltransferases and subsequently oxidized by TET proteins. The resulting 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are considered demethylation intermediates as well as stable epigenetic marks. To dissect the contributions of these cytosine modifying enzymes, we generated combinations of Tet knockout (KO) embryonic stem cells (ESCs) and systematically measured protein and DNA modification levels at the transition from naive to primed pluripotency. Whereas the increase of genomic 5-methylcytosine (5mC) levels during exit from pluripotency correlated with an upregulation of the de novo DNA methyltransferases DNMT3A and DNMT3B, the subsequent oxidation steps turned out to be far more complex. The strong increase of oxidized cytosine bases (5hmC, 5fC, and 5caC) was accompanied by a drop in TET2 levels, yet the analysis of KO cells suggested that TET2 is responsible for most 5fC formation. The comparison of modified cytosine and enzyme levels in Tet KO cells revealed distinct and differentiation-dependent contributions of TET1 and TET2 to 5hmC and 5fC formation arguing against a processive mechanism of 5mC oxidation. The apparent independent steps of 5hmC and 5fC formation suggest yet to be identified mechanisms regulating TET activity that may constitute another layer of epigenetic regulation.
Evolutionary algorithms converge towards evolved biological photonic structures
Authors: Barry Mamadou Aliou , Berthier Vincent , Wilts Bodo D. , Cambourieux Marie-Claire , Bennet Pauline , Pollès Rémi , Teytaud Olivier , Centeno Emmanuel , Biais Nicolas , Moreau Antoine
Published: July 2020

Nature features a plethora of extraordinary photonic architectures that have been optimized through natural evolution in order to more efficiently reflect, absorb or scatter light. While numerical optimization is increasingly and successfully used in photonics, it has yet to replicate any of these complex naturally occurring structures. Using evolutionary algorithms inspired by natural evolution and performing particular optimizations (maximize reflection for a given wavelength, for a broad range of wavelength or maximize the scattering of light), we have retrieved the most stereotypical natural photonic structures. Whether those structures are Bragg mirrors, chirped dielectric mirrors or the gratings on top of Morpho butterfly wings, our results indicate how such regular structures might have spontaneously emerged in nature and to which precise optical or fabrication constraints they respond. Comparing algorithms show that recombination between individuals, inspired by sexual reproduction, confers a clear advantage that can be linked to the fact that photonic structures are fundamentally modular: each part of the structure has a role which can be understood almost independently from the rest. Such anin silicoevolution also suggests original and elegant solutions to practical problems, as illustrated by the design of counter-intuitive anti-reflective coatings for solar cells.
Computational analysis of androgen receptor (AR) variants to decipher the relationship between protein stability and related-diseases
Authors: Chen Fangfang , Chen Xiaoqing , Jiang Fan , Leng Feng , Liu Wei , Gui Yaoting , Yu Jing
Published: July 2020

Although more than 1,000 androgen receptor (AR) mutations have been identified and these mutants are pathologically important, few theoretical studies have investigated the role of AR protein folding stability in disease and its relationship with the phenotype of the patients. Here, we extracted AR variant data from four databases: ARDB, HGMD, Cosmic, and 1,000 genome. 905 androgen insensitivity syndrome (AIS)-associated loss-of-function mutants and 168 prostate cancer-associated gain-of-function mutants in AR were found. We analyzed the effect of single-residue variation on the folding stability of AR by FoldX and guanidine hydrochloride denaturation experiment, and found that genetic disease-associated mutations tend to have a significantly greater effect on protein stability than gene polymorphisms. Moreover, AR mutants in complete androgen insensitivity syndrome (CAIS) tend to have a greater effect on protein stability than in partial androgen insensitive syndrome (PAIS). This study, by linking disease phenotypes to changes in AR stability, demonstrates the importance of protein stability in the pathogenesis of hereditary disease.
Vertical distribution of brittle star larvae in two contrasting coastal embayments: implications for larval transport
Authors: Guillam Morgane , Bessin Claire , Blanchet-Aurigny Aline , Cugier Philippe , Nicolle Amandine , Thiébaut Éric , Comtet Thierry
Published: July 2020

The ability of marine invertebrate larvae to control their vertical position shapes their dispersal pattern. In species characterized by large variations in population density, like many echinoderm species, larval dispersal may contribute to outbreak and die-off phenomena. A proliferation of the ophiuroidOphiocomina nigrawas observed for several years in western Brittany (France), inducing drastic changes on the benthic communities. We here studied the larval vertical distribution in this species and two co-occurring ophiuroid species,Ophiothrix fragilisandAmphiura filiformis, in two contrasting hydrodynamic environments: stratified in the bay of Douarnenez and well-mixed in the bay of Brest. Larvae were collected at 3 depths during 25 h within each bay. In the bay of Brest, all larvae were evenly distributed in the water column due to the intense vertical mixing. Conversely, in the bay of Douarnenez, a diel vertical migration was observed forO. nigra, with a night ascent of young larvae, and ontogenetic differences.These different patterns in the two bays mediate the effects of tidal currents on larval fluxes.O. fragilislarvae were mainly distributed above the thermocline which may favour larval retention within the bay, whileA. filiformislarvae, mostly concentrated near the bottom, were preferentially exported. This study highlighted the complex interactions between coastal hydrodynamics and specific larval traits, e.g. larval morphology, in the control of larval vertical distribution and larval dispersal.
A fully sustainable, self-poled, bio-waste based piezoelectric nanogenerator: electricity generation from pomelo fruit membrane
Authors: Bairagi Satyaranjan , Ghosh Saikat , Ali S. Wazed
Published: July 2020

A self-powered system is very much essential aspect in the recent trend to improve the working efficiency of the portable and wearable devices. Here, we have reported a fully sustainable, self-poled, bio-compatible, and bio-waste based piezoelectric energy harvester which has been made of Pomelo Fruit Membrane (PFM). PFM based piezoelectric generator (PFMBPEG) could generate ~ 6.4 V output voltage and ~ 7.44 μA output current directly, only by finger tapping on the device and registers a power density of ~ 12 μW cm−2 whereas, the same piezoelectric generator can generate ~ 15 V output voltage, 130 μA output current, and power density of ~ 487.5 μW cm−2 by using a full wave rectifier. The sensitivity and energy harvesting competence of the generator have also been assessed by attaching this nanogenerator into various parts of human body (as energy sources) such as wrist, elbow, finger, throat, jaws, leg and putting the device into ultrasonic bath and in every case, it could successfully generate voltage. Therefore, this bio-waste based energy harvester can be used as a power source for the different potable and wearable electronic goods where a small amount of energy is required, specifically in the biomedical applications (i.e., health monitoring, power source for the implantable devices and so on). Finally, mechanical stability the developed piezoelectric generator has been evaluated by cyclic bending test and it has been observed that there is no significant deformation of the PFM film even after 100 cycles.
Real-time metabolic profiling of oesophageal tumours reveals an altered metabolic phenotype to different oxygen tensions and to treatment with Pyrazinib
Authors: Buckley Amy M. , Dunne Margaret R. , Morrissey Maria E. , Kennedy Susan A. , Nolan Aoife , Davern Maria , Foley Emma K. , Clarke Niamh , Lysaght Joanne , Ravi Narayanasamy , O’Toole Dermot , MacCarthy Finbar , Reynolds John V. , Kennedy Breandán N. , O’Sullivan Jacintha
Published: July 2020

Oesophageal cancer is the 6th most common cause of cancer related death worldwide. The current standard of care for oesophageal adenocarcinoma (OAC) focuses on neoadjuvant therapy with chemoradiation or chemotherapy, however the 5-year survival rates remain at < 20%. To improve treatment outcomes it is critical to further investigate OAC tumour biology, metabolic phenotype and their metabolic adaptation to different oxygen tensions. In this study, by using human ex-vivo explants we demonstrated using real-time metabolic profiling that OAC tumour biopsies have a significantly higher oxygen consumption rate (OCR), a measure of oxidative phosphorylation compared to extracellular acidification rate (ECAR), a measure of glycolysis (p = 0.0004). Previously, we identified a small molecule compound, pyrazinib which enhanced radiosensitivity in OAC. Pyrazinib significantly inhibited OCR in OAC treatment-naïve biopsies (p = 0.0139). Furthermore, OAC biopsies can significantly adapt their metabolic rate in real-time to their environment. Under hypoxic conditions pyrazinib produced a significant reduction in both OCR (p = 0.0313) and ECAR in OAC treatment-naïve biopsies. The inflammatory secretome profile from OAC treatment-naïve biopsies is heterogeneous. OCR was positively correlated with three secreted factors in the tumour conditioned media: vascular endothelial factor A (VEGF-A), IL-1RA and thymic stromal lymphopoietin (TSLP). Pyrazinib significantly inhibited IL-1β secretion (p = 0.0377) and increased IL-3 (p = 0.0020) and IL-17B (p = 0.0181). Importantly, pyrazinib did not directly alter the expression of dendritic cell maturation markers or reduce T-cell viability or activation markers. We present a new method for profiling the metabolic rate of tumour biopsies in real-time and demonstrate the novel anti-metabolic and anti-inflammatory action of pyrazinib ex-vivo in OAC tumours, supporting previous findings in-vitro whereby pyrazinib significantly enhanced radiosensitivity in OAC.
Early evidence of fire in south-western Europe: the Acheulean site of Gruta da Aroeira (Torres Novas, Portugal)
Authors: Sanz Montserrat , Daura Joan , Cabanes Dan , Égüez Natalia , Carrancho Ángel , Badal Ernestina , Souto Pedro , Rodrigues Filipa , Zilhão João
Published: July 2020

The site of Gruta da Aroeira (Torres Novas, Portugal), with evidence of human occupancy dating to ca. 400 ka (Marine Isotope Stage 11), is one of the very few Middle Pleistocene localities to have provided a fossil hominin cranium associated with Acheulean bifaces in a cave context. The multi-analytic study reported here of the by-products of burning recorded in layer X suggests the presence of anthropogenic fires at the site, among the oldest such evidence in south-western Europe. The burnt material consists of bone, charcoal and, possibly, quartzite cobbles. These finds were made in a small area of the cave and in two separate occupation horizons. Our results add to our still-limited knowledge about the controlled use of fire in the Lower Palaeolithic and contribute to ongoing debates on the behavioural complexity of the Acheulean of Europe.
Blockade of the TLR4–MD2 complex lowers blood pressure and improves vascular function in a murine model of type 1 diabetes
Authors: de Oliveira Amanda Almeida , Faustino Josemar , Webb R. Clinton , Nunes Kenia Pedrosa
Published: July 2020

While the pathogenesis of diabetes-induced high blood pressure (BP) is not entirely clear, current evidence suggests that Toll-like receptor 4 (TLR4) is a key player in the mechanisms associated with hypertension. However, it is unknown whether this receptor affects BP under type 1 diabetes. Likewise, there is insufficient knowledge about the role of TLR4 in diabetes-associated vascular dysfunction of large arteries. To narrow these gaps, in this study, we investigated if blockade of the TLR4-MD2 complex impacts BP and vascular function in diabetic rats. We injected streptozotocin in male Sprague Dawley rats and treated them with a neutralizing anti-TLR4 antibody for 14 days. BP was directly measured in conscious animals at the end of the treatment. In another set of experiments, we excised the aorta from control and diabetic animals, and measured TLR4 and MD2—a co-receptor that confers functionality to TLR4—levels by Western blotting. We also performed functional studies and evaluated ROS levels with and without a pharmacological inhibitor for TLR4 as well as for MD2. Additionally, we scrutinized a large human RNA-Seq dataset of aortic tissue to assess the co-expression of TLR4, MD2, and subunits of the vascular NADPH oxidases under diabetes and hypertension. We report that (a) chronic blockade of the TLR4–MD2 complex lowers BP in diabetic animals; that (b) type 1 diabetes modulates the levels of MD2 expression in the aorta, but not TLR4, at least in the conditions evaluated in this study; and, that (c) acute inhibition of TLR4 or MD2 diminishes vascular contractility and reduces oxidative stress in the aorta of these animals. In summary, we show evidence that the TLR4–MD2 complex is involved in the mechanisms linking type 1 diabetes and hypertension.